Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether k...Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.展开更多
Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through iso...Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.展开更多
Objectives Primary prevention targeting modifiable risk factors would reduce the global burden of colorectal cancer,but the quantitative results are uncertain.We aimed to assess the global burden of colorectal cancer ...Objectives Primary prevention targeting modifiable risk factors would reduce the global burden of colorectal cancer,but the quantitative results are uncertain.We aimed to assess the global burden of colorectal cancer attributed to modifiable lifestyle factors and quantify the potential increase in life expectancy resulting from the elimination of these risk factors.Methods Based on the Global Burden of Disease Study 2021,we examined colorectal cancer deaths and disability-adjusted life years attributed to modifiable risk factors(including smoking,diet low in whole grains,diet low in milk,diet high in red meat,diet low in calcium,diet high in processed meat,and diet low in fiber)at the global,regional,and national levels from 1990 to 2021.The abridged period life table method was utilized to quantify the potential gain in life expectancy from eliminating these risk factors.Results Globally in 2021,57.1%of colorectal cancer deaths and 56.4%of disability-adjusted life years were preventable,with rates of 7.55(4.94–9.64)and 174.67(114.54–222.24)per 100,000 population,respectively.The modifiable burden has diminished in the high,high-middle,and low socio-demographic index quintiles and remained steady in the middle one.However,there is a concerning increase in the low-middle one.In 2021,the elimination of global colorectal cancer attributed to modifiable factors would increase the life expectancy for males and females by 0.107 and 0.109 years,respectively.Conclusion Our results quantitatively demonstrate the substantial burden reduction in colorectal cancer and the significant gain in life expectancy that can be achieved by eliminating modifiable lifestyle factors.展开更多
Objective:To understand the current status and changing trends in the lifetime risk of residents in Henan Province,China to develop and die from cancer.Methods:Lifetime risk was estimated using the Adjusted for Multip...Objective:To understand the current status and changing trends in the lifetime risk of residents in Henan Province,China to develop and die from cancer.Methods:Lifetime risk was estimated using the Adjusted for Multiple Primaries(AMP)method,incorporating cancer incidence,mortality,and all-cause mortality data from 55 cancer registries in Henan Province,China.Estimates were calculated overall and stratified by gender and area.The annual percent change(APC)in lifetime risk from 2010 to 2020,stratified by gender and cancer site,was estimated using a log-linear model.Results:In 2020,the lifetime risk of developing and dying from cancer was 30.19%(95%CI:29.63%-30.76%)and 23.62%(95%CI:23.28%-23.95%),respectively.These estimates were higher in men,with values of 31.22%(95%CI:30.59%-31.85%)for developing cancer and 26.73%(95%CI:26.29%-27.16%)for dying from cancer,compared with women,who had values of 29.02%(95%CI:28.12%-29.91%)and 20.08%(95%CI:19.51%-20.64%),respectively.There were also geographical differences,with higher estimates in urban areas compared with rural areas.Residents had the highest lifetime risk of developing lung cancer,with a rate of 6.94%,followed by breast cancer(4.14%),stomach cancer(3.95%),esophageal cancer(3.75%),and liver cancer(2.86%).Similarly,the highest lifetime risk of dying from cancer was observed for the following sites:lung(5.99%),stomach(3.60%),esophagus(3.39%),liver(2.78%),and colorectum(1.55%).Overall,the lifetime risk of developing cancer increased,with an APC of 0.75%(P<0.05).Varying trends were observed across different cancer sites.There were gradual decreases in nasopharynx,esophagus,stomach,and liver cancers.Conversely,increasing trends were noted for most other sites,with the highest APCs observed in thyroid,prostate,lymphoma,kidney,and gallbladder cancers.Conclusion:The lifetime risks of developing and dying from cancer were 30.19%and 23.62%,respectively.Variations in cancer risk across different regions,genders,specific cancer sites,and over calendar years provide important information for cancer prevention and policy making in the population.展开更多
Objective:To evaluate the impact of government-organized screening on the economic burden among patients with cervical cancer and precancerous lesions,and explore mediating pathways across diagnosis,initial treatment,...Objective:To evaluate the impact of government-organized screening on the economic burden among patients with cervical cancer and precancerous lesions,and explore mediating pathways across diagnosis,initial treatment,radiotherapy/chemotherapy,follow-up,and recurrence/progression/metastasis.Methods:A multicentre,nationwide survey across 5 disease courses was conducted from 26 hospitals in China.Multivariable regression and structural equation modeling were used to assess the effects of government-organized screening on economic burden by comparing government-organized screening with workplace check-up,self-paid check-up,and symptom-based detection.Results:Workplace check-up,self-paid check-up,and symptom-based detection were associated with progressively higher costs across diagnosis[β:1.10,95%confidence interval(CI):0.54±1.67;β:1.46,95%CI:1.00±1.92;andβ:1.68,95%CI:1.25±2.11,respectively],initial treatment(β:0.36,95%CI:0.18±0.55;β:0.51,95%CI:0.35±0.66;andβ:0.56,95%CI:0.42±0.70,respectively),and follow-up(β:0.63,95%CI:0.38±0.88;β:0.83,95%CI:0.61±1.04;andβ:0.85,95%CI:0.65±1.06,respectively)compared to government-organized screening(all P<0.05).Earlier clinical staging and greater use of lower-level hospitals mediated 44.74%±54.97%of cost differences in diagnosis,73.27%±85.04%in initial treatment,and 30.38%±54.73%in follow-up.Fifteen percent of the cost differences during initial treatment were related to lower overtreatment for precancerous lesions.Conclusions:Government-led cervical cancer screening was associated with lower economic burden with pathways involving earlier-stage diagnosis,reduced overtreatment,and decreased reliance on higher-level hospitals,suggesting potential clinical benefits,efficient resource use,and improved equity in cancer care.展开更多
1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of ca...1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of cancer is a complex interplay between genetic and environmental factors.2 In addition to genetic modifications,there is a growing body of evidence suggesting that epigenetic changes,which influence gene expression without modifying the DNA sequence,are playing an increasingly significant role in the development of cancer.DNA methylation,a key epigenetic mechanism,has been notably implicated in the early stages of cancer development,positioning it as a potential biomarker for cancer risk assessment.3 Studies have identified a diverse array of DNA methylation biomarkers for the early detection and diagnosis of cancer,utilizing DNA extracted from tissues,blood,stool,urine,and bowel lavage fluid.4 Research of DNA methylation has focused on two primary sources:peripheral blood mononuclear cell or white blood cell(WBC)DNA methylation,5 linked to cancer susceptibility and tumor-derived cell-free DNA(cfDNA)methylation,6 which has gained significant attention in recent years as a promising biomarker for cancer screening and diagnosis.展开更多
Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesio...Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.展开更多
BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth fac...BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.展开更多
Objective:To describe temporal changes associated with deployment of an optical character recognition(OCR)-enabled OneIdentity(One-ID)digital platform for rural cervical cancer screening,focusing on over-screening rat...Objective:To describe temporal changes associated with deployment of an optical character recognition(OCR)-enabled OneIdentity(One-ID)digital platform for rural cervical cancer screening,focusing on over-screening rates,CIN2+detection,colposcopy follow-up,and CIN2+management.Methods:A multi-county pre-post observational study was conducted in six rural counties in Shanxi,Yunnan,and Sichuan Provinces(2021±2024),encompassing 153,978 encounters.The digital platform integrates OCR identity capture,deterministic One-ID linkage,and real-time duplicate alerts.Over-screening proportions before and after digital deployment were compared,changes in CIN2+detection rate were evaluated,and colposcopy follow-up and CIN2+management were assessed.Differences were tested withχ2 or Fisher's exact tests.Results:Among 153,978 encounters,the proportion of over-screening decreased from 12.64%in 2023 to 0.17%in 2024 with an absolute reduction of 12.17%(95%CI:11.94±12.40;P<0.001).The share of women receiving a first screening within the preceding 3 y increased from 78.3%to 88.2%(P<0.001).Colposcopy completion improved from 64.1%to 84.9%.The CIN2+detection rate rose from 0.35%(2021±2023 pooled)to 0.67%in 2024(P<0.001)and CIN2+management completion increased from 56.0%to 76.2%(95%CI:13.3±27.2;P<0.001).These improvements were consistent across age groups,counties,and screening strategies.Conclusions:The OCR-enabled One-ID platform substantially reduced over-screening,increased CIN2+detection rate,and strengthened case follow-up/management,particularly where baseline tracking was weak,supporting scalable digital reinforcement of rural screening programmes.展开更多
Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic ...Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
Objective: The burden of gastric cancer(GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals fr...Objective: The burden of gastric cancer(GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to 2017.Methods: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates(ASIRs) were evaluated using cancer registry data from volumes X±XII of the Cancer Incidence in Five Continents(CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate(ASMR) and the Human Development Index(HDI).Results: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008±2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially females.Conclusions: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.展开更多
BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with...BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with unresectable EC.METHODS We retrospectively analyzed the clinical characteristics,toxic reactions,and survival information of EC patients aged≥75 years who underwent intensity-modulated RT at Lu’an Hospital of Anhui Medical University between January 2016 and September 2023.Kaplan-Meier analysis was used to draw the overall survival(OS)curves,and Cox regression analysis was employed to evaluate the influence of various clinical factors on the prognosis.RESULTS A total of 139 patients were enrolled.The median follow-up time was 52.0 months.The median OS was 20.0 months.The 1-year,2-year,3-year,and 5-year OS rates were 69.8%,38.7%,28.2%,and 17.5%,respectively.Univariate analysis showed that age,radiation dose,and chemotherapy had no significant impact on prognosis.Multivariate analysis indicated that clinical stage[Ⅲ-Ⅳa vsⅠ-Ⅱ,hazard ratio(HR)=2.421,95%confidence interval(CI):1.242-4.718,P=0.009;IVb vsⅠ-Ⅱ,HR=4.222,95%CI:1.888-9.438,P<0.001),Charlson comorbidity index(CCI)(0 vs≥1,HR=1.539,95%CI:1.015-2.332,P=0.042),and nutritional risk screening 2002(NRS2002)(<3 vs≥3,HR=2.491,95%CI:1.601-3.875,P<0.001)were independent prognostic factors for OS.CONCLUSION Our results suggest that CCI and NRS2002 were independent prognostic factors of OS for unresectable elderly EC patients undergoing RT.For elderly patients with EC,full attention should be given to biological age-related indicators,such as comorbidities and nutrition,when formulating treatment protocols.These factors should be considered in future clinical practice.展开更多
Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation...Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.展开更多
As peer reviewers of the World Journal of Gastroenterology,our weekly routine involves immersing ourselves in the newly published issue,particularly focusing on the realm of colorectal cancer(CRC)research.We diligentl...As peer reviewers of the World Journal of Gastroenterology,our weekly routine involves immersing ourselves in the newly published issue,particularly focusing on the realm of colorectal cancer(CRC)research.We diligently sift through various contributions,ranging from comprehensive reviews to original articles and other scholarly works.Through meticulous examination,we discern the most notable papers,delving into each with careful scrutiny to distill their merits and shortcomings.Undoubtedly,this undertaking demands considerable time and effort.Yet,it stands as an indispensable pursuit,affording us a profound comprehension of the latest breakthroughs in CRC research.Moreover,these meticulously curated selections furnish readers with invaluable resources,serving as enduring references for the nuanced exploration of this dynamic field.展开更多
Background:Esophageal cancer(EC)remains a global health challenge due to its poor prognosis.China and the United States of America(USA)represent two distinct epicenters of EC burden.Understanding the EC disparities in...Background:Esophageal cancer(EC)remains a global health challenge due to its poor prognosis.China and the United States of America(USA)represent two distinct epicenters of EC burden.Understanding the EC disparities in these two countries is vital for tailoring prevention strategies,optimizing treatment,and enhancing outcomes in both countries.Yet,there lacks a comprehensive comparison of EC characteristics between the two countries.Methods:In this multicenter,retrospective hospital-based study,we enrolled primary EC patients who received their initial treatment at one of 23 hospitals in China during 2016-2017.Using electronic medical records and cancer registration records,information on demographics,lifestyle,and clinicopathological characteristics(in-cluding tumor site,pathology,stage,metastases,differentiation,and treatment)were collected.Additionally,we compared these data with the clinicopathological information of invasive EC patients diagnosed in 2016-2017 from the Surveillance,Epidemiology,and End Results(SEER)database in the USA.Results:A total of 6,658 EC patients in China and 8,555 EC patients in the USA were included finally.85.5%(n=5,694)of EC were esophageal squamous cell carcinoma(ESCC)in China,while esophageal adenocarcinoma(EAC)was prominent in the USA(58.9%,n=5,041).Among EC patients with known staging,the proportion of early stage was higher in China compared to the USA(48.3%vs.30.5%).Among ESCC patients,early-stage cases were higher in China than in the USA(49.8%vs.31.8%),while among EAC patients,late-stage cases were higher in China than in the USA(77.3%vs.68.5%)(all P<0.001).In China,EC mainly occurred in the middle third(60.2%)of the esophagus,whereas in the USA,it was more common in the lower third(59.9%)of the organ.Compared with EC patients with known metastatic status in the USA,China had fewer cases of lymph node metastases(51.4%vs.57.7%)and distant metastases(7.9%vs.33.8%).Regarding treatment,China had more surgical therapy(53.7%vs.22.6%),less radiotherapy(35.6%vs.53.3%),and less chemotherapy(46.7%vs.59.7%)compared to the USA.Conclusions:This study reveals notable disparities in EC between China and the USA,encompassing epidemi-ological,clinicopathological,and treatment dimensions.These findings provide insight for tailored strategies addressing regional variations in clinicopathological and therapeutic characteristics.展开更多
Gastric cancer remains a significant global health challenge,causing a substantial number of cancer-related deaths,particularly in China.While the exact causes of gastric cancer are still being investigated,Helicobac-...Gastric cancer remains a significant global health challenge,causing a substantial number of cancer-related deaths,particularly in China.While the exact causes of gastric cancer are still being investigated,Helicobac-ter pylori(H.pylori)infection has been identified as the primary risk factor,which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time.Since the 1990s,numerous efforts have focused on assessing the effectiveness of H.pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment.This body of work,including several community-based interventions and meta-analyses,has shown a reduction in both the incidence of and mortality from gastric cancer following H.pylori treatment,alongside a decreased risk of metachronous gastric cancer.In this review,we seek to consolidate current knowledge on the effects of H.pylori treatment on gastric cancer prevention,its systemic consequences,cost-effectiveness,and the influence of antibiotic resistance and host characteristics on treatment outcomes.We further discuss the potential for precision primary prevention of H.pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.展开更多
BACKGROUND Depression is strongly associated with colorectal cancer(CRC).Few bibliometric analyses have systematically summarized the research focus and recent progress in this field.AIM To determine the research stat...BACKGROUND Depression is strongly associated with colorectal cancer(CRC).Few bibliometric analyses have systematically summarized the research focus and recent progress in this field.AIM To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between CRC and depression.METHODS Articles on depression in CRC patients were collected from the Web of Science Core Collection.CiteSpace and VOSviewer software were used to visualize bibliometric networks.RESULTS From 2001 to 2022,Supportive Care in Cancer,the United States,Tilburg University,and Mols were the most productive and influential journal,country,institution,and author name.Co-occurrence cluster analysis of keywords placed quality of life,anxiety,and psychological stress in the center of the visual network diagram.Further clustering was performed for the clusters with studies of the relevant mechanism of action,which showed that:(1)Cytokines have a role essential for the occurrence and development of depressive disorders in CRC;(2)MicroRNAs have a role essential for the development of depressive disorders in CRC;(3)Some anticancer drugs have pro-depressant activity;and(4)Selective serotonin reuptake inhibitors have both antitumor and antidepressant activity.CONCLUSION Life quality and psychological nursing of the cancer population were key topics.The roles of cytokines and microRNAs,the pro-depression activity of anticancer drugs and their antitumor properties deserve in-depth study.展开更多
The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from ...The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric analysis and visualization were conducted using VOSviewer(version 1.6.18)software and CiteSpace 6.1.R6(64-bit)Basic.A comprehensive compilation of 4722 English-language publications,covering the period from January 1,1991 to December 31,2022,was carefully identified and included in the analysis.Among the authors,“Ogino,Shuji”contributed the most publications in this field,while“Giovannucci,E”garnered the highest number of citations.The journal“Cancer Research”ranked first in both publication volume and citations.Institutionally,“Shanghai Jiao Tong University”emerged as the top contributor in terms of published articles,while“Harvard University”led in citation impact.In country-based analysis,the United States held the top position in both publication output and citations,closely followed by China.The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.展开更多
Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies ...Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).展开更多
基金funded by the National Natural Science Foundation of China(No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501400-2023ZD0501402)+4 种基金Beijing Hospitals Authority’s Ascent Plan(DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202325)China Postdoctoral Science Foundation(2024M760152)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(No.BMU2022XKQ004)Science Foundation of Peking University Cancer Hospital(Nos.BJCH2024BJ02,XKFZ2410,BJCH2025CZ04,and 2022-27)。
文摘Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.
基金supported by the National Natural Science Foundation of China(Grant No.32170738)the National Medical Research Council of Singapore(Grant No.NMRC/CBRG/0013/2012).
文摘Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.
基金supported by the National Natural Science Foundation of China(grant number:82404340)the CAMS Innovation Fund for Medical Science(grant number:2021-I2M-1–067)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(grant number:LTGY23H260004)the Beijing Natural Science Foundation(grant number:Z240004).
文摘Objectives Primary prevention targeting modifiable risk factors would reduce the global burden of colorectal cancer,but the quantitative results are uncertain.We aimed to assess the global burden of colorectal cancer attributed to modifiable lifestyle factors and quantify the potential increase in life expectancy resulting from the elimination of these risk factors.Methods Based on the Global Burden of Disease Study 2021,we examined colorectal cancer deaths and disability-adjusted life years attributed to modifiable risk factors(including smoking,diet low in whole grains,diet low in milk,diet high in red meat,diet low in calcium,diet high in processed meat,and diet low in fiber)at the global,regional,and national levels from 1990 to 2021.The abridged period life table method was utilized to quantify the potential gain in life expectancy from eliminating these risk factors.Results Globally in 2021,57.1%of colorectal cancer deaths and 56.4%of disability-adjusted life years were preventable,with rates of 7.55(4.94–9.64)and 174.67(114.54–222.24)per 100,000 population,respectively.The modifiable burden has diminished in the high,high-middle,and low socio-demographic index quintiles and remained steady in the middle one.However,there is a concerning increase in the low-middle one.In 2021,the elimination of global colorectal cancer attributed to modifiable factors would increase the life expectancy for males and females by 0.107 and 0.109 years,respectively.Conclusion Our results quantitatively demonstrate the substantial burden reduction in colorectal cancer and the significant gain in life expectancy that can be achieved by eliminating modifiable lifestyle factors.
基金supported by Henan Province Science and Technology Tackling Key Issues Project(grant number:232102310166).
文摘Objective:To understand the current status and changing trends in the lifetime risk of residents in Henan Province,China to develop and die from cancer.Methods:Lifetime risk was estimated using the Adjusted for Multiple Primaries(AMP)method,incorporating cancer incidence,mortality,and all-cause mortality data from 55 cancer registries in Henan Province,China.Estimates were calculated overall and stratified by gender and area.The annual percent change(APC)in lifetime risk from 2010 to 2020,stratified by gender and cancer site,was estimated using a log-linear model.Results:In 2020,the lifetime risk of developing and dying from cancer was 30.19%(95%CI:29.63%-30.76%)and 23.62%(95%CI:23.28%-23.95%),respectively.These estimates were higher in men,with values of 31.22%(95%CI:30.59%-31.85%)for developing cancer and 26.73%(95%CI:26.29%-27.16%)for dying from cancer,compared with women,who had values of 29.02%(95%CI:28.12%-29.91%)and 20.08%(95%CI:19.51%-20.64%),respectively.There were also geographical differences,with higher estimates in urban areas compared with rural areas.Residents had the highest lifetime risk of developing lung cancer,with a rate of 6.94%,followed by breast cancer(4.14%),stomach cancer(3.95%),esophageal cancer(3.75%),and liver cancer(2.86%).Similarly,the highest lifetime risk of dying from cancer was observed for the following sites:lung(5.99%),stomach(3.60%),esophagus(3.39%),liver(2.78%),and colorectum(1.55%).Overall,the lifetime risk of developing cancer increased,with an APC of 0.75%(P<0.05).Varying trends were observed across different cancer sites.There were gradual decreases in nasopharynx,esophagus,stomach,and liver cancers.Conversely,increasing trends were noted for most other sites,with the highest APCs observed in thyroid,prostate,lymphoma,kidney,and gallbladder cancers.Conclusion:The lifetime risks of developing and dying from cancer were 30.19%and 23.62%,respectively.Variations in cancer risk across different regions,genders,specific cancer sites,and over calendar years provide important information for cancer prevention and policy making in the population.
基金supported by the Bill&Melinda Gates Foundation(Grant no.OPP1216421)CAMS Innovation Fund for Medical Sciences[CIFMS](Grant no.2021-I2M-1-004)。
文摘Objective:To evaluate the impact of government-organized screening on the economic burden among patients with cervical cancer and precancerous lesions,and explore mediating pathways across diagnosis,initial treatment,radiotherapy/chemotherapy,follow-up,and recurrence/progression/metastasis.Methods:A multicentre,nationwide survey across 5 disease courses was conducted from 26 hospitals in China.Multivariable regression and structural equation modeling were used to assess the effects of government-organized screening on economic burden by comparing government-organized screening with workplace check-up,self-paid check-up,and symptom-based detection.Results:Workplace check-up,self-paid check-up,and symptom-based detection were associated with progressively higher costs across diagnosis[β:1.10,95%confidence interval(CI):0.54±1.67;β:1.46,95%CI:1.00±1.92;andβ:1.68,95%CI:1.25±2.11,respectively],initial treatment(β:0.36,95%CI:0.18±0.55;β:0.51,95%CI:0.35±0.66;andβ:0.56,95%CI:0.42±0.70,respectively),and follow-up(β:0.63,95%CI:0.38±0.88;β:0.83,95%CI:0.61±1.04;andβ:0.85,95%CI:0.65±1.06,respectively)compared to government-organized screening(all P<0.05).Earlier clinical staging and greater use of lower-level hospitals mediated 44.74%±54.97%of cost differences in diagnosis,73.27%±85.04%in initial treatment,and 30.38%±54.73%in follow-up.Fifteen percent of the cost differences during initial treatment were related to lower overtreatment for precancerous lesions.Conclusions:Government-led cervical cancer screening was associated with lower economic burden with pathways involving earlier-stage diagnosis,reduced overtreatment,and decreased reliance on higher-level hospitals,suggesting potential clinical benefits,efficient resource use,and improved equity in cancer care.
基金supported by the Beijing Nova Program of Science and Technology(grant number:20230484397)the National Natural Science Foundation of China(grant number:82273726).
文摘1.Introduction With an estimate of 19,976,499 newly diagnosed cases and 9,743,832 deaths occurred in 2022 worldwide,cancer continues to impose a significant health and economic burden worldwide.1 The development of cancer is a complex interplay between genetic and environmental factors.2 In addition to genetic modifications,there is a growing body of evidence suggesting that epigenetic changes,which influence gene expression without modifying the DNA sequence,are playing an increasingly significant role in the development of cancer.DNA methylation,a key epigenetic mechanism,has been notably implicated in the early stages of cancer development,positioning it as a potential biomarker for cancer risk assessment.3 Studies have identified a diverse array of DNA methylation biomarkers for the early detection and diagnosis of cancer,utilizing DNA extracted from tissues,blood,stool,urine,and bowel lavage fluid.4 Research of DNA methylation has focused on two primary sources:peripheral blood mononuclear cell or white blood cell(WBC)DNA methylation,5 linked to cancer susceptibility and tumor-derived cell-free DNA(cfDNA)methylation,6 which has gained significant attention in recent years as a promising biomarker for cancer screening and diagnosis.
基金funded by the National Natural Science Foundation of China(Grant No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(Grant Nos.2023ZD0501400-2023ZD0501402)+3 种基金Beijing Hospitals Authority’s Ascent Plan(Grant No.DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(Grant No.ZLRK202325)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(Grant No.BMU2022XKQ004)the Science Foundation of Peking University Cancer Hospital(Grant Nos.BJCH2024BJ02,XKFZ2410,and 2022-27).
文摘Objective:The key molecular events signifying the Helicobacter pylori-induced gastric carcinogenesis process are largely unknown.Methods:Bulk tissue-proteomics profiling were leveraged across multi-stage gastric lesions from Linqu(n=166)and Beijing sets(n=99)and single-cell transcriptomic profiling(n=18)to decipher key molecular signatures of H.pylori-related gastric lesion progression and gastric cancer(GC)development.The association of key proteins association with gastric lesion progression and GC development were prospectively studied building on follow-up of the Linqu set and UK Biobank(n=48,529).Results:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis(ρ=0.784,correlation P=1.80×10^(−36))were identified.RNA expression of genes encoding 13 up-and 15 down-regulated key proteins displayed trending alterations in the transition from normal gastric epithelium to intestinal metaplasia,then to malignant cells.A 15-tissue protein panel integrating these signatures demonstrated potential for targeting individuals at high risk for progressing to gastric neoplasia(OR=7.22,95%CI:1.31-39.72 for the high-score group).A 4-circulating protein panel may be used as non-invasive markers predicting the risk of GC development(hazard ratio=3.73,95%confidence interval:1.63-8.54,high-risk vs.low-risk populations,area under the curve=0.75).Conclusions:Concordant proteomics signatures associated with H.pylori infection and gastric carcinogenesis were unveiled with potential as biomarkers for targeted prevention strategies.
文摘BACKGROUND Ovarian cancer(OC)is the most lethal gynecological cancer among females,and its early diagnosis could help for better outcomes of the patients.AIM To investigate the utility of serum insulin-like growth factors-binding proteins 2(IGFBP2),secreted phosphoprotein 1(SPP1),thrombospondin 1 protein(TSP1)and D-dimer levels in addition to currently used biomarkers[cancer antigen 125(CA125)and human epididymis protein 4(HE4)]in the diagnosis of epithelial OC(EOC).METHODS This is a case-control study that included fifty females diagnosed with EOC,10 females with benign ovarian masses recruited from the Egyptian National Cancer Institute,and 30 healthy females as a control group.All subjects were assessed for serum HE4,CA125,IGFBP2,TSP1 and SPP1 measurement by enzyme-linkedimmunosorbent assay.RESULTS There was a statistically significant difference in serum levels between EOC,benign ovarian masses,and healthy control groups regarding CA125 and SPP1(P<0.001 for both markers),while HE4 and IGFBP2 increased significantly in EOC compared to healthy control groups(P<0.001 for all markers)with no significant difference between EOC and benign ovarian masses groups.However,there was no statistically significant difference among EOC,benign ovarian masses,and healthy control groups regarding the TSP1 serum levels(P=0.051).Receiver operating characteristic analysis revealed that combined assessment of SPP1 with CA125 or TSP1 increased the diagnosis of EOC patients to a sensitivity,specificity,and area under curve of(93.3%,100%,0.968;respectively,P<0.001).CONCLUSION SPP1 may be a potential marker for the differentiation between benign and malignant ovarian masses,while IGFBP2 can differentiate between healthy females and females with ovarian masses.Combining SPP1 with CA125 or TSP1 provides high sensitivity and specificity for the detection of EOC patients.
基金supported by the Chongqing Tencent Sustainable Development Foundation through the project"Comprehensive Prevention and Control Demonstration Project for Eliminating Cervical Cancer and Breast Cancer in Low Health Resource Areas of China"(Project No.SD20240904145730)by the Tencent Sustainable Social Value(SSV)Inclusive Health Lab(Project No.SSVPJ202307060001)。
文摘Objective:To describe temporal changes associated with deployment of an optical character recognition(OCR)-enabled OneIdentity(One-ID)digital platform for rural cervical cancer screening,focusing on over-screening rates,CIN2+detection,colposcopy follow-up,and CIN2+management.Methods:A multi-county pre-post observational study was conducted in six rural counties in Shanxi,Yunnan,and Sichuan Provinces(2021±2024),encompassing 153,978 encounters.The digital platform integrates OCR identity capture,deterministic One-ID linkage,and real-time duplicate alerts.Over-screening proportions before and after digital deployment were compared,changes in CIN2+detection rate were evaluated,and colposcopy follow-up and CIN2+management were assessed.Differences were tested withχ2 or Fisher's exact tests.Results:Among 153,978 encounters,the proportion of over-screening decreased from 12.64%in 2023 to 0.17%in 2024 with an absolute reduction of 12.17%(95%CI:11.94±12.40;P<0.001).The share of women receiving a first screening within the preceding 3 y increased from 78.3%to 88.2%(P<0.001).Colposcopy completion improved from 64.1%to 84.9%.The CIN2+detection rate rose from 0.35%(2021±2023 pooled)to 0.67%in 2024(P<0.001)and CIN2+management completion increased from 56.0%to 76.2%(95%CI:13.3±27.2;P<0.001).These improvements were consistent across age groups,counties,and screening strategies.Conclusions:The OCR-enabled One-ID platform substantially reduced over-screening,increased CIN2+detection rate,and strengthened case follow-up/management,particularly where baseline tracking was weak,supporting scalable digital reinforcement of rural screening programmes.
基金supported by the National Science Fund for Excellent Young Scholars(NSFC-82322058)the Program of National Natural Science Foundation of China(NSFC-82103929,NSFC-82273713)+10 种基金the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the National Science Fund for Distinguished Young Scholars of Hubei Province of China(2023AFA046)the Fundamental Research Funds for the Central Universities(WHU:2042022kf1205)Fundamental Research Funds for the Central Universities(WHU:2042022kf1031)for Ying Zhuthe Fundamental Research Funds for the Central Universities(2042022rc0026,2042023kf1005)for Xiao-Ping Miaothe Knowledge Innovation Program of Wuhan(whkxjsj011,2023020201010073)for Jian-Bo Tianthe Science and Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University(znpy2019060)for Yong-Chang Weithe Distinguished Young Scholars of China(NSFC-81925032)the Key Program of National Natural Science Foundation of China(NSFC-82130098)the Youth Program of National Natural Science Foundation of China(NSFC-82003547)the Program of Health Commission of Hubei Province(WJ2023M045)。
文摘Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
基金funded by the National Natural Science Foundation of China (Grant No. 82273721)the National Natural Science Foundation of China (Grant No. 81974492)+1 种基金the Capital’s Funds for Health Improvement and Research Conflict of interest statement (Grant No. 2024-1G-4023)CAMS Innovation Fund for Medical Sciences (CIFMS)(Grant No. 2021-I2M-C&T-B-049)。
文摘Objective: The burden of gastric cancer(GC) across different age groups needs updating. We determined the GC global, regional, and national burden profiles and changes in incidence for 3 sequential 5-year intervals from 2003 to 2017.Methods: The latest incidence and mortality estimates of GC from 185 countries and regions were extracted from the GLOBOCAN 2022 database. The 5-year interval age-standardised incidence rates(ASIRs) were evaluated using cancer registry data from volumes X±XII of the Cancer Incidence in Five Continents(CI5). Correlation analysis was used to evaluate the relationship between ASIR or the age-standardised mortality rate(ASMR) and the Human Development Index(HDI).Results: There was an estimated global 968,000 new GC cases and 660,000 deaths in 2022, with male predominance. GC ASIRs and ASMRs were 9.2 and 6.1 per 100,000 persons, respectively. East Asia had the highest burden, with 53.8% of cases and 48.2% of deaths among all geographic regions. There was a significant correlation between ASIR and HDI. Over three 5-year intervals from 2003 to 2017, the incidence of GC notably decreased in most countries but peaked at 2008±2012 in New Zealand, Turkey, and South Africa. Several countries in Europe, Oceania, and America suggest an increasingly concerning trend among younger individuals, especially females.Conclusions: GC is a significant health issue, especially among males and in geographic regions with an HDI, such as eastern Asia. While the incidence of GC is decreasing in many countries due to prevention efforts and improved treatments, a rising trend persists among younger individuals. Comprehensive prevention strategies tailored to different age patterns are clearly needed.
基金Supported by the Science and Technology Program of Lu’an,No.2022 Lakj042.
文摘BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with unresectable EC.METHODS We retrospectively analyzed the clinical characteristics,toxic reactions,and survival information of EC patients aged≥75 years who underwent intensity-modulated RT at Lu’an Hospital of Anhui Medical University between January 2016 and September 2023.Kaplan-Meier analysis was used to draw the overall survival(OS)curves,and Cox regression analysis was employed to evaluate the influence of various clinical factors on the prognosis.RESULTS A total of 139 patients were enrolled.The median follow-up time was 52.0 months.The median OS was 20.0 months.The 1-year,2-year,3-year,and 5-year OS rates were 69.8%,38.7%,28.2%,and 17.5%,respectively.Univariate analysis showed that age,radiation dose,and chemotherapy had no significant impact on prognosis.Multivariate analysis indicated that clinical stage[Ⅲ-Ⅳa vsⅠ-Ⅱ,hazard ratio(HR)=2.421,95%confidence interval(CI):1.242-4.718,P=0.009;IVb vsⅠ-Ⅱ,HR=4.222,95%CI:1.888-9.438,P<0.001),Charlson comorbidity index(CCI)(0 vs≥1,HR=1.539,95%CI:1.015-2.332,P=0.042),and nutritional risk screening 2002(NRS2002)(<3 vs≥3,HR=2.491,95%CI:1.601-3.875,P<0.001)were independent prognostic factors for OS.CONCLUSION Our results suggest that CCI and NRS2002 were independent prognostic factors of OS for unresectable elderly EC patients undergoing RT.For elderly patients with EC,full attention should be given to biological age-related indicators,such as comorbidities and nutrition,when formulating treatment protocols.These factors should be considered in future clinical practice.
基金supported by grants from the Beijing Nova Program (No. Z201100006820069)CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2021-I2M-1-023, 2021-I2M-1-010)Talent Incentive Program of Cancer Hospital Chinese Academy of Medical Sciences (Hope Star)。
文摘Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.
基金Supported by The Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713The Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06。
文摘As peer reviewers of the World Journal of Gastroenterology,our weekly routine involves immersing ourselves in the newly published issue,particularly focusing on the realm of colorectal cancer(CRC)research.We diligently sift through various contributions,ranging from comprehensive reviews to original articles and other scholarly works.Through meticulous examination,we discern the most notable papers,delving into each with careful scrutiny to distill their merits and shortcomings.Undoubtedly,this undertaking demands considerable time and effort.Yet,it stands as an indispensable pursuit,affording us a profound comprehension of the latest breakthroughs in CRC research.Moreover,these meticulously curated selections furnish readers with invaluable resources,serving as enduring references for the nuanced exploration of this dynamic field.
基金supported by the National Key R&D Program of China(grant number:2022YFC3600805,2016YFC1302502).
文摘Background:Esophageal cancer(EC)remains a global health challenge due to its poor prognosis.China and the United States of America(USA)represent two distinct epicenters of EC burden.Understanding the EC disparities in these two countries is vital for tailoring prevention strategies,optimizing treatment,and enhancing outcomes in both countries.Yet,there lacks a comprehensive comparison of EC characteristics between the two countries.Methods:In this multicenter,retrospective hospital-based study,we enrolled primary EC patients who received their initial treatment at one of 23 hospitals in China during 2016-2017.Using electronic medical records and cancer registration records,information on demographics,lifestyle,and clinicopathological characteristics(in-cluding tumor site,pathology,stage,metastases,differentiation,and treatment)were collected.Additionally,we compared these data with the clinicopathological information of invasive EC patients diagnosed in 2016-2017 from the Surveillance,Epidemiology,and End Results(SEER)database in the USA.Results:A total of 6,658 EC patients in China and 8,555 EC patients in the USA were included finally.85.5%(n=5,694)of EC were esophageal squamous cell carcinoma(ESCC)in China,while esophageal adenocarcinoma(EAC)was prominent in the USA(58.9%,n=5,041).Among EC patients with known staging,the proportion of early stage was higher in China compared to the USA(48.3%vs.30.5%).Among ESCC patients,early-stage cases were higher in China than in the USA(49.8%vs.31.8%),while among EAC patients,late-stage cases were higher in China than in the USA(77.3%vs.68.5%)(all P<0.001).In China,EC mainly occurred in the middle third(60.2%)of the esophagus,whereas in the USA,it was more common in the lower third(59.9%)of the organ.Compared with EC patients with known metastatic status in the USA,China had fewer cases of lymph node metastases(51.4%vs.57.7%)and distant metastases(7.9%vs.33.8%).Regarding treatment,China had more surgical therapy(53.7%vs.22.6%),less radiotherapy(35.6%vs.53.3%),and less chemotherapy(46.7%vs.59.7%)compared to the USA.Conclusions:This study reveals notable disparities in EC between China and the USA,encompassing epidemi-ological,clinicopathological,and treatment dimensions.These findings provide insight for tailored strategies addressing regional variations in clinicopathological and therapeutic characteristics.
基金supported by the National Natural Science Founda-tion of China(grant number:82273704)the Beijing Hospitals Author-ity Clinical Medicine Development of Special Funding Support(grant number:ZLRK202325)+6 种基金Beijing Hospitals Authority’s Ascent Plan,Na-tional Key R&D Program of China(grant number:2018YFA0507503)Peking University Medicine Fund for world’s leading discipline or disci-pline cluster development(grant number:BMU2022XKQ004)Science Foundation of Peking University Cancer Hospital(grant number:2022-27)and Science Foundation of Peking University Cancer Hospital(grant number:XKFZ2410)he funding sources had no role in study designin the collection,analysis,and interpretation of datain the writing of the reportor in the decision to submit the article for publication.The funders had no role in study design,data collection,data analysis,data interpretation,or writing of the report.
文摘Gastric cancer remains a significant global health challenge,causing a substantial number of cancer-related deaths,particularly in China.While the exact causes of gastric cancer are still being investigated,Helicobac-ter pylori(H.pylori)infection has been identified as the primary risk factor,which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time.Since the 1990s,numerous efforts have focused on assessing the effectiveness of H.pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment.This body of work,including several community-based interventions and meta-analyses,has shown a reduction in both the incidence of and mortality from gastric cancer following H.pylori treatment,alongside a decreased risk of metachronous gastric cancer.In this review,we seek to consolidate current knowledge on the effects of H.pylori treatment on gastric cancer prevention,its systemic consequences,cost-effectiveness,and the influence of antibiotic resistance and host characteristics on treatment outcomes.We further discuss the potential for precision primary prevention of H.pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.
文摘BACKGROUND Depression is strongly associated with colorectal cancer(CRC).Few bibliometric analyses have systematically summarized the research focus and recent progress in this field.AIM To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between CRC and depression.METHODS Articles on depression in CRC patients were collected from the Web of Science Core Collection.CiteSpace and VOSviewer software were used to visualize bibliometric networks.RESULTS From 2001 to 2022,Supportive Care in Cancer,the United States,Tilburg University,and Mols were the most productive and influential journal,country,institution,and author name.Co-occurrence cluster analysis of keywords placed quality of life,anxiety,and psychological stress in the center of the visual network diagram.Further clustering was performed for the clusters with studies of the relevant mechanism of action,which showed that:(1)Cytokines have a role essential for the occurrence and development of depressive disorders in CRC;(2)MicroRNAs have a role essential for the development of depressive disorders in CRC;(3)Some anticancer drugs have pro-depressant activity;and(4)Selective serotonin reuptake inhibitors have both antitumor and antidepressant activity.CONCLUSION Life quality and psychological nursing of the cancer population were key topics.The roles of cytokines and microRNAs,the pro-depression activity of anticancer drugs and their antitumor properties deserve in-depth study.
基金Supported by Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric analysis and visualization were conducted using VOSviewer(version 1.6.18)software and CiteSpace 6.1.R6(64-bit)Basic.A comprehensive compilation of 4722 English-language publications,covering the period from January 1,1991 to December 31,2022,was carefully identified and included in the analysis.Among the authors,“Ogino,Shuji”contributed the most publications in this field,while“Giovannucci,E”garnered the highest number of citations.The journal“Cancer Research”ranked first in both publication volume and citations.Institutionally,“Shanghai Jiao Tong University”emerged as the top contributor in terms of published articles,while“Harvard University”led in citation impact.In country-based analysis,the United States held the top position in both publication output and citations,closely followed by China.The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.
基金funded by Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A)National Natural Science Foundation of China(Grant No.82103677)National Science and Technology Major Projects of China(Grant No.2019ZX09732-001)。
文摘Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).
