Introduction: Smoking and non-smoking lung cancer have many differences in clinical feature. But those may be the result of interference due to differences in pathological type, as most smoking patients suffer squmous...Introduction: Smoking and non-smoking lung cancer have many differences in clinical feature. But those may be the result of interference due to differences in pathological type, as most smoking patients suffer squmous cell lung cancer and non-smokings tend to get adenocarcinoma. This study was conducted on the specific histological type-lung adenocarcinoma-to avoid histological bias and to reveal the true effect of smoking. Methods: A total of 2222 patients with lung adenocarcinoma confirmed by histological or cytological evidence were enrolled from January 1, 1999 to December 31, 2004. Differences in clinical features and prognosis between non-smoking and smoking patients were analyzed.Chisquare test was used for univariate comparisons. Univariate probability of survival was computed using Kaplan-Meier estimate and compared to using the log-rank test. Cox proportional hazards regression analysis was used to evaluate the risk of death. Results: There were 777 current smokers (34.96%), 197 former smokers (8.87%) and 1248 non-smoking patients (56.17%). 860 non-smoking patients (68.91%) were female, compared with 6.31% among current smokers and 4.06% among former smokers (p < 0.001). Non-smoking patients had an earlier age at diagnosis (p < 0.001) and a better response to chemotherapy (p < 0.001) compared to current smoking patients. Current smoking correlated with lower cell differentiation (p < 0.001) and worse prognosis (p = 0.0024). After multivariate analysis, smoking was identified as an independent negative prognostic factor (HR, 1.302;95% CI, 1.011 - 1.6780, p = 0.041). No difference in prognosis was observed according to smoking conditions in smoking patients. Conclusions: Significent differences exist in clinical features and prognosis between non-smoking and smoking lung adenocarcinoma patients. There is a strong evidence that non-smoking lung adenocarcinoma should be regard as different disease.展开更多
Background:Immune checkpoint inhibitors(ICIs)have been included in various neoadjuvant therapy(NAT)regimens for non-small cell lung cancer(NSCLC).However,due to the relatively short period for the use of ICIs in NAT,p...Background:Immune checkpoint inhibitors(ICIs)have been included in various neoadjuvant therapy(NAT)regimens for non-small cell lung cancer(NSCLC).However,due to the relatively short period for the use of ICIs in NAT,patients’clinical outcomes with different regimens are uncertain.Our study aims to examine the efficacy of neoadjuvant immunotherapy(NAIT)for NSCLC patients and compare the overall survival(OS)and event-free survival(EFS)of patients receiving different NAT regimens.Methods:This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1,2016 and July 31,2022.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients.Results:With a median follow-up of 27.5 months,the 1-year OS rates were 98.8%and 96.2%,and the 2-year OS rates were 96.6%and 85.8%in patients of the NAIT and neoadjuvant chemotherapy(NACT)group,respectively(hazard ratio[HR],0.339;95%confidence interval[CI],0.160-0.720;P=0.003).The 1-year EFS rates were 96.0%and 88.0%,and the 2-year EFS rates were 92.0%and 77.7%for patients in the NAIT and NACT groups,respectively(HR,0.438;95%CI,0.276-0.846;P=0.010).For patients who did not achieve pathological complete response(pCR),significantly longer OS(P=0.012)and EFS(P=0.019)were observed in patients receiving NAIT than those receiving NACT.Different NAT regimens had little effect on surgery and the postoperative length of stay(6[4,7]days vs.6[4,7]days,Z=-0.227,P=0.820).Conclusions:NAIT exhibited superior efficacy to NACT for NSCLC,resulting in longer OS and EFS.The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.展开更多
Background: Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer...Background: Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females-even after excluding the influence of smoking;but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.Methods: Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.Results: With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females;the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma;after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.Conclusions: Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored;most known risk factors were more harmful to non-smoking women;further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.展开更多
Esophageal cancer(EC)is a common cancer and is histopathologically classified into esophageal squamous cell carcinoma and esophageal adenocarcinoma.EC is a worldwide public health issue because of late diagnosis and l...Esophageal cancer(EC)is a common cancer and is histopathologically classified into esophageal squamous cell carcinoma and esophageal adenocarcinoma.EC is a worldwide public health issue because of late diagnosis and lack of effective therapy.In contrast to standard tumor biopsies,liquid biopsies are emerging as a tool which is minimally invasive that can complement or even substitute more classical approaches.Specifically,cell-free DNA(cfDNA)has shown promise in cancer-related clinical applications.Indeed,cfDNA has been shown to be an effective circulating biomarker for non-invasive cancer diagnosis and monitoring of cancer patients.Although the clinical application of cfDNA has been reported on other cancers,few studies have evaluated its use in EC.Here,we review this relevant literature and discuss limitations and advantages of its application in the diagnosis and monitoring of EC.展开更多
Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reas...Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reasons for activation of KIAA1429(also known as VIRMA,an RNA methyltransferase)and its underlying mechanism in lung adenocarcinoma(LUAD)remain largely unexplored.In this study,we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD.Methods:Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase.The in vitro and in vivo functions of KIAA1429 were investigated.Transcriptome sequencing,methylated RNA immunoprecipitation sequencing(MeRIP-seq),m6A dot blot assays and RNA immunoprecipitation(RIP)were performed to confirm the modified gene mediated by KIAA1429.RNA stability assays were used to detect the half-life of the target gene.Results:Copy number amplification drove higher expression of KIAA1429 in LUAD,whichwas correlatedwith poor overall survival.Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD.Mechanistically,the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays.We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner.Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA,leading to enhanced YTH m6A RNA binding protein 2(YTHDF2,the m6A“reader”)-dependent BTG2 mRNA stability and promoted the expression of BTG2;thus,participating in the tumorigenesis of LUAD.Conclusions:Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis,which may provide a novel view on the targeted molecular therapy of LUAD.展开更多
Adenosine-to-inosine(A-to-I)RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis.Here,we evaluated a total of 19,316 RNA editing sites in the tiss...Adenosine-to-inosine(A-to-I)RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis.Here,we evaluated a total of 19,316 RNA editing sites in the tissues of 80 lung adenocarcinoma(LUAD)patients from our Nanjing Lung Cancer Cohort(NJLCC)and 486 LUAD patients from the TCGA database.The global RNA editing level was significantly increased in tumor tissues and was highly heterogeneous across patients.The high RNA editing level in tumors was attributed to both RNA(ADAR1 expression)and DNA alterations(mutation load).Consensus clustering on RNA editing sites revealed a new molecular subtype(EC3)that was associated with the poorest prognosis of LUAD patients.Importantly,the new classification was independent of classic molecular subtypes based on gene expression or DNA methylation.We further proposed a simplified model including eight RNA editing sites to accurately distinguish the EC3 subtype in our patients.The model was further validated in the TCGA dataset and had an area under the curve(AUC)of the receiver operating characteristic curve of 0.93(95%CI:0.91-0.95).In addition,we found that LUAD cell lines with the EC3 subtype were sensitive to four chemotherapy drugs.These findings highlighted the importance of RNA editing events in the tumorigenesis of LUAD and provided insight into the application of RNA editing in the molecular subtyping and clinical treatment of cancer.展开更多
Background:Tracheal,bronchus,and lung(TBL)cancer imposes a high disease burden globally,and its pattern varies greatly across regions and countries.This study aimed to explore the global burden and temporal trends of ...Background:Tracheal,bronchus,and lung(TBL)cancer imposes a high disease burden globally,and its pattern varies greatly across regions and countries.This study aimed to explore the global burden and temporal trends of TBL cancer from 1990 to 2019.Methods:Data on incidence,mortality,and disability-adjusted life years(DALYs)metrics(number,crude rate,and age-standardized rates),and the attributable risk fraction of DALY of TBL cancer from 1990 to 2019 in 21 Global Burden of Disease(GBD)regions,four World Bank income regions,204 countries and territories,and the globe were obtained from the up-to-date GBD 2019 study.We applied estimated annual percentage changes(EAPCs)to the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and age-standardized DALY rate(ASDR)to quantify the temporal trends of the TBL cancer burden from 1990-2019.Associations of EAPC of age-standardized rates with universal health coverage(UHC)index at the national level were evaluated with Pearson correlation analysis.Results:Globally,approximately 2,260,000 new TBL cancer cases,2,042,600 deaths,and 45,858,000 DALYs were reported in 2019.Combination of all modifiable risk factors,behavioral,environmental,and metabolic risk factors accounted for 79.1%,66.4%,33.3%,and 7.9%of global lung cancer DALYs,respectively.The overall ASIR(EAPC:-0.1[95%confidence interval[CI]:-0.2,-0.1]),ASMR(EAPC:-0.3[95%CI:-0.4,-0.3]),and ASDR(EAPC:-0.7[95%CI:-0.7,-0.6])decreased from 1990 to 2019.The highest mortality rate of TBL cancer occurred in the>85-year-old age group for both sexes among high-income countries(HICs)and upper-middle-income countries(UMCs),and in males aged 80-84 years and females aged>85 years in lower middle-income countries(LMCs).HICs experienced the largest declines in ASIR(-12.6%),ASMR(-20.3%),and ASDR(-27.8%)of TBL cancer between 1990 and 2019,while UMCs had the highest increases in ASIR(16.7%)and ASMR(8.0%)over the period.Eleven(52.4%),14(66.7%),and 15(71.4%)regions of the 21 GBD regions experienced descending trends in ASIR,ASMR,and ASDR of TBL cancer between 1990 and 2019,respectively,with the greatest mean decrease per year(EAPC:-1.7[95%CI:-2.0,-1.5]for ASIR,-1.9[95%CI:-2.2,-1.7]for ASMR,and-2.2[95%CI:-2.5,-2.0]for ASDR)being observed in eastern Europe.The ASIR,ASMR,and ASDR of TBL cancer were deemed to be in decreasing trends in 85,91,and 104 countries and territories,with the largest decrease in Bahrain(EAPC:-3.0[95%CI:-3.3,-2.7]for ASIR,-3.0[95%CI:-3.3,-2.6]for ASMR,and-3.4[95%CI:-3.8,-3.1]for ASDR).ASIR(r=0.524),ASMR(r=0.411),and ASDR(r=0.353)of TBL cancer were positively associated with UHC index at the national level in 2019.Conclusions:The TBL cancer burden shows a downward trend at the global level but varies greatly across regions and countries.A decreasing trend in the TBL cancer burden was observed in the most of the 21 GBD regions and 204 countries from 1990 to 2019.UMCs had the highest burden of TBL cancer and showed the largest increases in ASIR and ASMR.展开更多
Familial risk of lung cancer has been widely studied but whether this association holds in non-smoking females is largely unknown.We sought to determine the relationship between a family history of cancer and lung can...Familial risk of lung cancer has been widely studied but whether this association holds in non-smoking females is largely unknown.We sought to determine the relationship between a family history of cancer and lung cancer risk among Chinese non-smoking females based on a multi-center prospective population-based cohort study involving 547,218 individuals between 2013 and 2019.A total of 1620 lung cancer cases occurred during a median follow-up of 3.9 years.Multivariable Cox regression showed that a family history of lung cancer in first-degree relatives significantly increased the risk of lung cancer(HR:1.50,95%CI:1.29,1.75,P<0.001).Relative to those with no relatives affected,the risk of lung cancer was 51%higher in females with one relative affected(HR:1.51,95%CI:1.29-1.76,P<0.001),123%higher in females with two relatives affected(HR:2.23,95%CI:1.57-3.15,P<0.001)and 143%higher in females with three or more relatives affected(HR:2.43,95%CI:1.21-4.91,P=0.013).Two nested case control studies stratified by age at diagnosis were conducted to verify potential disparities in this association between the early or late onset of lung cancer.A family history of lung cancer in first-degree relatives was significantly correlated with an elevated risk of lung cancer for both cases before and after age 65(OR:1.36,95%CI:1.07-1.74,P=0.013;OR:1.64,95%CI:1.15-2.33,P=0.006).Our analysis confirmed the importance of familial history of cancers on lung cancer risk in non-smoking females and highlighted the possibility of interaction between genetic and environmental effect on lung cancer.展开更多
To the Editor:Lung invasive mucinous adenocarcinoma(LIMA)is regarded as a subtype of invasive lung adenocarcinoma(LUAD).No significant differences exist in the overall survival(OS)or recurrence-free survival(RFS)betwe...To the Editor:Lung invasive mucinous adenocarcinoma(LIMA)is regarded as a subtype of invasive lung adenocarcinoma(LUAD).No significant differences exist in the overall survival(OS)or recurrence-free survival(RFS)between lobectomy and sublobectomy in clinical stage IA non small cell lung cancer(NSCLC)≤2 cm.[1]Besides,the studies on surgical methods in early LIMA are limited.In this study,we reviewed the clinicopathological features of LIMA and compared its prognosis under different surgical methods.展开更多
文摘Introduction: Smoking and non-smoking lung cancer have many differences in clinical feature. But those may be the result of interference due to differences in pathological type, as most smoking patients suffer squmous cell lung cancer and non-smokings tend to get adenocarcinoma. This study was conducted on the specific histological type-lung adenocarcinoma-to avoid histological bias and to reveal the true effect of smoking. Methods: A total of 2222 patients with lung adenocarcinoma confirmed by histological or cytological evidence were enrolled from January 1, 1999 to December 31, 2004. Differences in clinical features and prognosis between non-smoking and smoking patients were analyzed.Chisquare test was used for univariate comparisons. Univariate probability of survival was computed using Kaplan-Meier estimate and compared to using the log-rank test. Cox proportional hazards regression analysis was used to evaluate the risk of death. Results: There were 777 current smokers (34.96%), 197 former smokers (8.87%) and 1248 non-smoking patients (56.17%). 860 non-smoking patients (68.91%) were female, compared with 6.31% among current smokers and 4.06% among former smokers (p < 0.001). Non-smoking patients had an earlier age at diagnosis (p < 0.001) and a better response to chemotherapy (p < 0.001) compared to current smoking patients. Current smoking correlated with lower cell differentiation (p < 0.001) and worse prognosis (p = 0.0024). After multivariate analysis, smoking was identified as an independent negative prognostic factor (HR, 1.302;95% CI, 1.011 - 1.6780, p = 0.041). No difference in prognosis was observed according to smoking conditions in smoking patients. Conclusions: Significent differences exist in clinical features and prognosis between non-smoking and smoking lung adenocarcinoma patients. There is a strong evidence that non-smoking lung adenocarcinoma should be regard as different disease.
基金supported by grants from the National Natural Science Foundation of China(Nos.82273129,82002451)the National Key Research and Development Program of China(No.2021YFC2500900)+3 种基金Beijing Nova Program(No.20230484267)the Chinese Academy of Medical Sciences Initiative for Innovative Medicine(Nos.2021-I2M-1-015,2024-I2M-C&T-C-008,2022-I2M-C&T-B-055,2022-I2M-C&T-B-060,2023-I2M-C&T-B-078)Central Health Research Key Projects(No.2022ZD17)Research Project of the Institute(No.LC2019L01).
文摘Background:Immune checkpoint inhibitors(ICIs)have been included in various neoadjuvant therapy(NAT)regimens for non-small cell lung cancer(NSCLC).However,due to the relatively short period for the use of ICIs in NAT,patients’clinical outcomes with different regimens are uncertain.Our study aims to examine the efficacy of neoadjuvant immunotherapy(NAIT)for NSCLC patients and compare the overall survival(OS)and event-free survival(EFS)of patients receiving different NAT regimens.Methods:This study retrospectively included 308 NSCLC patients treated with different NAT regimens and subsequent surgery in National Cancer Center between August 1,2016 and July 31,2022.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the prognosis of patients.Results:With a median follow-up of 27.5 months,the 1-year OS rates were 98.8%and 96.2%,and the 2-year OS rates were 96.6%and 85.8%in patients of the NAIT and neoadjuvant chemotherapy(NACT)group,respectively(hazard ratio[HR],0.339;95%confidence interval[CI],0.160-0.720;P=0.003).The 1-year EFS rates were 96.0%and 88.0%,and the 2-year EFS rates were 92.0%and 77.7%for patients in the NAIT and NACT groups,respectively(HR,0.438;95%CI,0.276-0.846;P=0.010).For patients who did not achieve pathological complete response(pCR),significantly longer OS(P=0.012)and EFS(P=0.019)were observed in patients receiving NAIT than those receiving NACT.Different NAT regimens had little effect on surgery and the postoperative length of stay(6[4,7]days vs.6[4,7]days,Z=-0.227,P=0.820).Conclusions:NAIT exhibited superior efficacy to NACT for NSCLC,resulting in longer OS and EFS.The OS and EFS benefits were also observed among patients in the NAIT group who did not achieve pCR.
基金National Key Research and Development Program of China, Non-profit Central Research Institute Fund of China(No. 2018YFC1315000)National Natural Science Foundation of China(No. 8187102812)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Nos. 2020PT330001, 2019PT320027, 2019PT320023, 2018RC320010, and 3332019005)
文摘Background: Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females-even after excluding the influence of smoking;but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.Methods: Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.Results: With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females;the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma;after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.Conclusions: Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored;most known risk factors were more harmful to non-smoking women;further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.
文摘Esophageal cancer(EC)is a common cancer and is histopathologically classified into esophageal squamous cell carcinoma and esophageal adenocarcinoma.EC is a worldwide public health issue because of late diagnosis and lack of effective therapy.In contrast to standard tumor biopsies,liquid biopsies are emerging as a tool which is minimally invasive that can complement or even substitute more classical approaches.Specifically,cell-free DNA(cfDNA)has shown promise in cancer-related clinical applications.Indeed,cfDNA has been shown to be an effective circulating biomarker for non-invasive cancer diagnosis and monitoring of cancer patients.Although the clinical application of cfDNA has been reported on other cancers,few studies have evaluated its use in EC.Here,we review this relevant literature and discuss limitations and advantages of its application in the diagnosis and monitoring of EC.
基金Science Fund for Creative Research Groups of the National Natural Science Foundation of China,Grant/Award Number:81521004National Natural Science Foundation of China,Grant/Award Numbers:81922061,82172992,81903391,81702266+2 种基金Research Unit of Prospective Cohort of Cardiovascular Diseases and Cancers,Chinese Academy of Medical Sciences,Grant/Award Number:2019RU038Natural Science Foundation of Jiangsu Province,Grant/Award Numbers:BK20211253,BK20190148Postgraduate Research&Practice Innovation Program of Jiangsu Province,Grant/Award Number:KYCX18_0195。
文摘Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reasons for activation of KIAA1429(also known as VIRMA,an RNA methyltransferase)and its underlying mechanism in lung adenocarcinoma(LUAD)remain largely unexplored.In this study,we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD.Methods:Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase.The in vitro and in vivo functions of KIAA1429 were investigated.Transcriptome sequencing,methylated RNA immunoprecipitation sequencing(MeRIP-seq),m6A dot blot assays and RNA immunoprecipitation(RIP)were performed to confirm the modified gene mediated by KIAA1429.RNA stability assays were used to detect the half-life of the target gene.Results:Copy number amplification drove higher expression of KIAA1429 in LUAD,whichwas correlatedwith poor overall survival.Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD.Mechanistically,the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays.We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner.Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA,leading to enhanced YTH m6A RNA binding protein 2(YTHDF2,the m6A“reader”)-dependent BTG2 mRNA stability and promoted the expression of BTG2;thus,participating in the tumorigenesis of LUAD.Conclusions:Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis,which may provide a novel view on the targeted molecular therapy of LUAD.
基金supported by the National Natural Science Foundation of China(81922061,82072579,81521004,81973123and 81871885)the National Key Research and Development Project(2017YFC0907905)Research Unit of Prospective Cohort of Cardiovascular Diseases and Cancer,Chinese Academy of Medical Sciences(2019RU038)。
文摘Adenosine-to-inosine(A-to-I)RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis.Here,we evaluated a total of 19,316 RNA editing sites in the tissues of 80 lung adenocarcinoma(LUAD)patients from our Nanjing Lung Cancer Cohort(NJLCC)and 486 LUAD patients from the TCGA database.The global RNA editing level was significantly increased in tumor tissues and was highly heterogeneous across patients.The high RNA editing level in tumors was attributed to both RNA(ADAR1 expression)and DNA alterations(mutation load).Consensus clustering on RNA editing sites revealed a new molecular subtype(EC3)that was associated with the poorest prognosis of LUAD patients.Importantly,the new classification was independent of classic molecular subtypes based on gene expression or DNA methylation.We further proposed a simplified model including eight RNA editing sites to accurately distinguish the EC3 subtype in our patients.The model was further validated in the TCGA dataset and had an area under the curve(AUC)of the receiver operating characteristic curve of 0.93(95%CI:0.91-0.95).In addition,we found that LUAD cell lines with the EC3 subtype were sensitive to four chemotherapy drugs.These findings highlighted the importance of RNA editing events in the tumorigenesis of LUAD and provided insight into the application of RNA editing in the molecular subtyping and clinical treatment of cancer.
基金This study was funded by grants from the National Key Research and Development Program of China,Nonprofit Central Research Institute Fund of China(No.2018YFC1315000)National Natural Science Foun-dation of China(No.81871885)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2019PT320027).
文摘Background:Tracheal,bronchus,and lung(TBL)cancer imposes a high disease burden globally,and its pattern varies greatly across regions and countries.This study aimed to explore the global burden and temporal trends of TBL cancer from 1990 to 2019.Methods:Data on incidence,mortality,and disability-adjusted life years(DALYs)metrics(number,crude rate,and age-standardized rates),and the attributable risk fraction of DALY of TBL cancer from 1990 to 2019 in 21 Global Burden of Disease(GBD)regions,four World Bank income regions,204 countries and territories,and the globe were obtained from the up-to-date GBD 2019 study.We applied estimated annual percentage changes(EAPCs)to the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and age-standardized DALY rate(ASDR)to quantify the temporal trends of the TBL cancer burden from 1990-2019.Associations of EAPC of age-standardized rates with universal health coverage(UHC)index at the national level were evaluated with Pearson correlation analysis.Results:Globally,approximately 2,260,000 new TBL cancer cases,2,042,600 deaths,and 45,858,000 DALYs were reported in 2019.Combination of all modifiable risk factors,behavioral,environmental,and metabolic risk factors accounted for 79.1%,66.4%,33.3%,and 7.9%of global lung cancer DALYs,respectively.The overall ASIR(EAPC:-0.1[95%confidence interval[CI]:-0.2,-0.1]),ASMR(EAPC:-0.3[95%CI:-0.4,-0.3]),and ASDR(EAPC:-0.7[95%CI:-0.7,-0.6])decreased from 1990 to 2019.The highest mortality rate of TBL cancer occurred in the>85-year-old age group for both sexes among high-income countries(HICs)and upper-middle-income countries(UMCs),and in males aged 80-84 years and females aged>85 years in lower middle-income countries(LMCs).HICs experienced the largest declines in ASIR(-12.6%),ASMR(-20.3%),and ASDR(-27.8%)of TBL cancer between 1990 and 2019,while UMCs had the highest increases in ASIR(16.7%)and ASMR(8.0%)over the period.Eleven(52.4%),14(66.7%),and 15(71.4%)regions of the 21 GBD regions experienced descending trends in ASIR,ASMR,and ASDR of TBL cancer between 1990 and 2019,respectively,with the greatest mean decrease per year(EAPC:-1.7[95%CI:-2.0,-1.5]for ASIR,-1.9[95%CI:-2.2,-1.7]for ASMR,and-2.2[95%CI:-2.5,-2.0]for ASDR)being observed in eastern Europe.The ASIR,ASMR,and ASDR of TBL cancer were deemed to be in decreasing trends in 85,91,and 104 countries and territories,with the largest decrease in Bahrain(EAPC:-3.0[95%CI:-3.3,-2.7]for ASIR,-3.0[95%CI:-3.3,-2.6]for ASMR,and-3.4[95%CI:-3.8,-3.1]for ASDR).ASIR(r=0.524),ASMR(r=0.411),and ASDR(r=0.353)of TBL cancer were positively associated with UHC index at the national level in 2019.Conclusions:The TBL cancer burden shows a downward trend at the global level but varies greatly across regions and countries.A decreasing trend in the TBL cancer burden was observed in the most of the 21 GBD regions and 204 countries from 1990 to 2019.UMCs had the highest burden of TBL cancer and showed the largest increases in ASIR and ASMR.
基金supported by Ministry of Finance and National Health Commission of the People’s Republic of China,National Key R&D Pro-gram of China(Grant number:2018YFC1315000/2018YFC1315001)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Grant number:2019PT320027 and 2020PT330001)+1 种基金CAMS Innovation Fund for Medical Science(Grant number:2019-I2M-2-002)Sanming Project of Medicine in Shenzhen(Grant number:SZSM201911015).
文摘Familial risk of lung cancer has been widely studied but whether this association holds in non-smoking females is largely unknown.We sought to determine the relationship between a family history of cancer and lung cancer risk among Chinese non-smoking females based on a multi-center prospective population-based cohort study involving 547,218 individuals between 2013 and 2019.A total of 1620 lung cancer cases occurred during a median follow-up of 3.9 years.Multivariable Cox regression showed that a family history of lung cancer in first-degree relatives significantly increased the risk of lung cancer(HR:1.50,95%CI:1.29,1.75,P<0.001).Relative to those with no relatives affected,the risk of lung cancer was 51%higher in females with one relative affected(HR:1.51,95%CI:1.29-1.76,P<0.001),123%higher in females with two relatives affected(HR:2.23,95%CI:1.57-3.15,P<0.001)and 143%higher in females with three or more relatives affected(HR:2.43,95%CI:1.21-4.91,P=0.013).Two nested case control studies stratified by age at diagnosis were conducted to verify potential disparities in this association between the early or late onset of lung cancer.A family history of lung cancer in first-degree relatives was significantly correlated with an elevated risk of lung cancer for both cases before and after age 65(OR:1.36,95%CI:1.07-1.74,P=0.013;OR:1.64,95%CI:1.15-2.33,P=0.006).Our analysis confirmed the importance of familial history of cancers on lung cancer risk in non-smoking females and highlighted the possibility of interaction between genetic and environmental effect on lung cancer.
基金supported by the National Key R&D Program of China(No.2022YFC2407404)National High-Level Hospital Clinical Research Funding(Nos.2022-PUMCH-A-018 and 2022-PUMCH-C-043)+2 种基金Special Research Fund for Central Universities,Peking Union Medical College(No.2022-I2M-C&T-B-060)Beijing Hope Run Special Fund of Cancer Foundation of China(No.LC2021L01)the Beijing Municipal Science&Technology Commission(No.Z211100002921058).
文摘To the Editor:Lung invasive mucinous adenocarcinoma(LIMA)is regarded as a subtype of invasive lung adenocarcinoma(LUAD).No significant differences exist in the overall survival(OS)or recurrence-free survival(RFS)between lobectomy and sublobectomy in clinical stage IA non small cell lung cancer(NSCLC)≤2 cm.[1]Besides,the studies on surgical methods in early LIMA are limited.In this study,we reviewed the clinicopathological features of LIMA and compared its prognosis under different surgical methods.
