Current algorithms for screening and surveillance for colon cancer are valuable, but may be limited by the underlying nature of the targeted neoplastic lesions. Although part of the success of adenoma removal relates ...Current algorithms for screening and surveillance for colon cancer are valuable, but may be limited by the underlying nature of the targeted neoplastic lesions. Although part of the success of adenoma removal relates to interruption of so-called "adenoma-carcinoma sequence", an alternate serrated pathway to colon cancer may pose difficulties with the ultimate results achieved by traditional colonoscopic methods. The endpoint carcinoma in this unique pathway may be derived from a dysplastic serrated adenoma. These tend to be located primarily in the right colon, especially in females, and are frequently associated with co-existent colon cancer. Unfortunately, however, there are few, if any, other identifiable risk factors, including age or family history of colon polyps or colon cancer. Moreover, this alternate serrated pathway may itself also be quite biologically heterogeneous as reflected in sessile serrated adenomas (SSA) with virtually exclusive molecular signatures defined by the presence of either BRAF or KRAS mutations. Screening algorithms in the future may need to be modified and individualized, depending on new information that likely will emerge on the natural history of these biologically heterogeneous lesions that differs from traditional adenomatous polyps.展开更多
Texture and color enhancement imaging(TXI)has been developed as a novel image-enhancing endoscopy.However,the effectiveness of TXI detecting adenomas is inferior to narrow band imaging.Thus,future studies will need to...Texture and color enhancement imaging(TXI)has been developed as a novel image-enhancing endoscopy.However,the effectiveness of TXI detecting adenomas is inferior to narrow band imaging.Thus,future studies will need to focus on investigating the feasibility of such combination in clinical settings in order to provide patients with more accurate diagnoses.展开更多
AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus,...AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or “high-risk” adenomas), and rated each trial’s risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence).CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.展开更多
AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenom...AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.展开更多
AIM： Recent laboratory and epidemiological studies suggest that vitamin D is a potential agent for colorectal cancer prevention. Its function is partially mediated by the vitamin D receptor （VDR）. The aim of this s...AIM： Recent laboratory and epidemiological studies suggest that vitamin D is a potential agent for colorectal cancer prevention. Its function is partially mediated by the vitamin D receptor （VDR）. The aim of this study was to investigate whether a novel G （allele ‘U’g〉A （allele ‘u’ polymorphism （Tru9I） in the VDR intron 8 region is associated with risk for colorectal adenoma in a colonoscopy-based case-control study. METHODS： Genotyping for a total of 391 subjects was carried out through PCR and restriction fragment length polymorphism. RESULTS： The frequencies of ‘U’ and ‘u’ alleles were 89.3% and 10.7%, respectively. The ‘Uu’ and ‘uu’ genotypes were associated with decreased risk for adenoma （OR, 0.71; 95%CI, 0.40-1.25）. The inverse association was more pronounced for multiple adenomas and adenomas that were larger had moderate or greater dysplasia, or were sessile： the odds ratios （ORs） were, 0.51 （95%CI, 0.21-1.24）, 0.37 （95%CI, 0.11-1.28）, 0.68 （95%CI, 0.33- 1.41）, and 0.36 （95%CI, 0.13-0.97） respectively. In joint/ combined analyses, inverse associations were more obvious among those who had at least one ‘u’ allele and also were younger （OR, 0.60; 95%CI, 0.26-1.37）, women （OR, 0.38; 95%CI, 0.17-0.88）, did not smoke （OR, 0.39; 95%CI, 0.13-1.23）, or took NSAID （OR, 0.38; 95%CI, 0.12-1.25）, but no evidence existed for interactions with calcium or vitamin D intake.CONCLUSION： Our findings suggest that the VDR TrugI polymorphism may be associated with lower risk for colorectal adenoma, particularly in interaction with various risk factors, but not with calcium or vitamin D.展开更多
AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-...AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.展开更多
AIM: To assess the extent and reasons of non- compliance in surveillance for patients undergoing polypectomy of large (≥ 1 cm) colorectal adenomas. METHODS: Between 1995 and 2002, colorectal adenomas ≥ 1 cm were dia...AIM: To assess the extent and reasons of non- compliance in surveillance for patients undergoing polypectomy of large (≥ 1 cm) colorectal adenomas. METHODS: Between 1995 and 2002, colorectal adenomas ≥ 1 cm were diagnosed in 210 patients and subsequently documented at the Erlangen Registry of Colorectal Polyps. One hundred and fi fty-eight patients (75.2%) could be contacted by telephone and agreed to be interviewed. Additionally, records were obtained from the treating physicians. RESULTS: Fifty-four out of 158 patients (34.2%) neglected any surveillance. Reasons for non-compliance included lack of knowledge concerning surveillance intervals (45.8%), no symptoms (29.2%), fear of examination (18.8%) or old age/severe illness (6.3%). In a multivariate analysis, the factors including female gender (P = 0.036) and age > 62 years (P = 0.016) proved to be signif icantly associated with non-compliance in surveillance. CONCLUSION: Efforts to increase compliance in surveillance are of utmost importance. This applies particularly to women’s compliance. Effective strategies for avoiding metachronous colorectal adenoma and cancer should focus on both the improvement in awareness and knowledge of patients and information about physicians for surveillance.展开更多
Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: Th...Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: The cases were defined as patients with advanced adenomas and the controls were patients with nonadvanced adenomas. Clinical data were extracted from the hospital information system. Missing data were imputed with the multiple imputation of chained equations method, and the effect of smoking on the risk of advanced adenomas was calculated by binary logistic regression models to obtain odds ratios (ORs) and 95% confidence interval. Results: Current smoking rate in patients with advanced adenomas was significantly higher than that in patients with nonadvanced adenomas (31.6% VS 23.1%), the OR of advanced adenoma for current smoking compared with nonsmoking was 1.54 (1.09, 2.18), P = 0.013, and the weighted ORs ranged from 1.50 (1.01, 2.23) to 1.58 (1.09, 2.30), and the results of sensitivity analyses were still consistent. Conclusion: In adults with Han ethnicity in South China, current smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas.展开更多
BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristi...BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were evaluated.Clinical data including laboratory results,colonoscopy findings,and pathology reports were collected.Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic regression.The performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve analysis.RESULTS The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin levels.The novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation groups.Calibration curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP.CONCLUSION The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.展开更多
OBJECTIVES:To systematically review the efficacy and safety of Jianpi formulas(健脾剂)in reducing the recurrence of colorectal adenoma(CRA)after polypectomy.METHODS:Randomized controlled trials(RCTs)investigating Jian...OBJECTIVES:To systematically review the efficacy and safety of Jianpi formulas(健脾剂)in reducing the recurrence of colorectal adenoma(CRA)after polypectomy.METHODS:Randomized controlled trials(RCTs)investigating Jianpi formulas for CRA post-polypectomy were systematically retrieved from eight electronic databases.The quality of the methodology was assessed using the Cochrane collaboration tool.The Grades of Recommendations Assessment Development and Evaluation(GRADE)approach was employed for evidence assessment.Statistical analyses were conducted using Statistics and Data Analysis(STATA)17(StataCorp(College Station,TX,USA)and Review Manager(RevMan)5.4(The Cochrane Collaboration(London,UK).RESULTS:The Meta-analysis,encompassing 18 RCTs with 1838 patients,revealed that Jianpi formulas significantly outperformed postoperative routine treatment.It demonstrated a reduction in the half-year recurrence rate[relative risk(RR)=0.41,95%confidence interval(CI)=0.33-0.49,Z=9.08,P<0.00001],the oneyear recurrence rate[RR=0.58,95%CI=0.49-0.69,Z=6.12,P<0.00001],and an enhancement in the clinical effective rate[RR=1.27,95%CI=1.19-1.36,Z=7.06,P<0.00001].The half-year recurrence rate and the clinical effective rate were medium-quality evidence.The one-year recurrence rate was low-quality evidence.Additionally,Jianpi formulas appear to be safe and do not increase adverse reactions compared to postoperative routine treatment alone.CONCLUSION:Jianpi formulas exhibit efficacy in reducing postoperative half-year and one-year recurrence rates while improving the clinical effective rate after polypectomy for CRA.展开更多
BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs,including the colon.Accordingly,studies aimed at developing therapies targeting this pathway in var...BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs,including the colon.Accordingly,studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression.Although Numb,Itch,and seven in absentia homolog-1(Siah-1)have been shown to contribute to the regulation of Notch signaling,their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date.AIM To evaluate Numb,Itch,and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior.METHODS Expression of Notch-1,Numb,Itch,and Siah-1 was investigated in 50 colorectal carcinomas,30 adenomas,and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(PCR)analyses.RESULTS In contrast to Notch-1,which is expressed at higher levels in tumor tissues and adenomas,expression of Numb,Itch,and Siah-1 was stronger and more frequent in normal mucosa(P<0.01).There was a positive correlation between Notch-1 expression and high histological grade,the presence of lymph node metastasis,and advanced-stage tumors,whereas expression of Numb,Itch,and Siah-1 was absent or reduced in tumors with these clinicopathological parameters(P<0.05).In survival analysis,expression of Notch was related to poor prognosis but that of Numb,Itch,and Siah-1 correlated with improved survival(P<0.05).Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis(P<0.05).CONCLUSION Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb,Itch,and Siah-1 expression is associated with carcinogenesis.Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma(CRC)progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.展开更多
Objective:The aim of this study was to investigate lipid disorders and lipid peroxidation associated with the malignant transformation of colorectal adenoma.Methods:Analyses were based on data from 100 subjects with h...Objective:The aim of this study was to investigate lipid disorders and lipid peroxidation associated with the malignant transformation of colorectal adenoma.Methods:Analyses were based on data from 100 subjects with histologically confirmed adenomas(cases) and 50 adenoma-free control subjects,all of whom had colonoscopy.The subjects were divided into two groups:those with no adenoma and those with adenoma.According to subsite of adenomas the subjects with adenoma were divided into group of distal adenoma and group of proximal adenoma.According to histology of adenomas the subjects with adenoma were divided into group of villiform adenoma and group of tubular + tubulo-villous adenoma.Among the groups,the serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),lowdensity lipoprotein cholesterol(LDL-C),and lipid peroxidation product malondialdehyde(MDA) were compared in all the patients.Results:Plasma total cholesterol and MDA level in group of adenomas were significantly higher than that in group of control subjects,but plasma HDL-C level was low in group of adenomas(P<0.05).Plasma total cholesterol and MDA levels were positively related to distal and villiform adenomas(P<0.05).Conclusion:The findings suggest that altered lipid metabolism may be differentially associated with colorectal adenomas.展开更多
AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cy...AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.展开更多
Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic al...Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas.Among crucial roles of epigenetic alterations,gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms.Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes.Each epigenotype cooperates with specific genetic alterations,suggesting that they represent different molecular carcinogenic pathways.Precursor lesions of CRC,such as conventional and serrated adenomas,already show similar methylation accumulation to CRC,and can therefore be classified into those epigenotypes of CRC.In addition,specific DNA methylation already occurs in the normal colonic mucosa,which might be utilized for prediction of the personal CRC risk.DNA methylation is suggested to occur at an earlier stage than carcinoma formation,and may predict the molecular basis for future development of CRC.Here,we review DNA methylation and CRC classification,and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis,prediction of the prognosis and the response to therapy of CRC.展开更多
Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoido...Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy.Since CRC develops slowly from precancerous lesions,early detection can reduce both the incidence and mortality of the disease.Fecal occult blood test is a widely used non-invasive screening tool for CRC.Although fecal occult blood test is simple and cost-effective in screening CRC,there is room for improvement in terms of the accuracy of the test.Genetic dysregulations have been found to play an important role in CRC development.With better understanding of the molecular basis of CRC,there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC.In this review,the molecular basis of CRC development,the characteristics and applications of different non-invasive molecular biomarkers,as well as the technologies available for the detection were discussed.This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state,colorectal adenoma.展开更多
AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected...AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.展开更多
To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODSPubMed and EMBASE databases were searched until March 2016 for the articles reporting on t...To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODSPubMed and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers,including:C-reactive protein(CRP),interleukin-6(IL-6),and tumor necros is factor-alpha(TNF-α)and risk of colorectal adenoma.Random-effects models were used to calculate summary odds ratios(ORs)with 95%CIs for the highest vs lowest category of exposure.Heterogeneity was assessed by using the Q test and I<sup>2</sup>statistic.Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTSA total of 14 case-control studies were included.Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary(OR=1.23,95%CI:0.98-1.54;I<sup>2</sup>=54%,P<sub>heterogeneity</sub>=0.01)in the general analysis,but significant increased odds when considering only advanced adenoma(OR=1.59,95%CI:1.09-2.32;I<sup>2</sup>=44%,P<sub>heterogeneity</sub>=0.15).Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma.Five studies examined the association between circulating levels of TNF-αand colorectal adenoma risk,including a total of 1,568 cases and 2,832 controls.The summary OR for the highest vs the lowest category of exposure was 1.00(95%CI:0.77-1.29).The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls.The summary OR for the highest vs the lowest category of exposure was 1.19(95%CI:0.92-1.55).CONCLUSIONSummary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk.The role of potential confounding factors should be further evaluated.展开更多
AIM To investigate the clinical utility of biological age(BA) measurement in screening colonoscopy for the detection of colorectal adenomas in the average-risk population.METHODS A consecutive series of asymptomatic s...AIM To investigate the clinical utility of biological age(BA) measurement in screening colonoscopy for the detection of colorectal adenomas in the average-risk population.METHODS A consecutive series of asymptomatic subjects aged ≥ 30 years who underwent colonoscopy in routine check-ups were enrolled. Colorectal adenoma was classified according to size, number, and location. BAs were calculated using the MEDIAGETM Biological Age Measurement System.RESULTS A total of 2696 subjects were investigated(1876 men and 820 women). The mean chronological age(CA) was 46.0 years and the mean BA was 44.7 years. Metabolic syndrome(MS) was diagnosed in 218 subjects(8.1%). The prevalence of overall colorectal adenoma was 23.1%(622/2,696). When the subjects were divided into four groups based on BA(≤ 39 years; 40-49 years; 50-59 years; ≥ 60 years), the prevalence of colorectal adenoma was increased as BA increased(P < 0.001). Colorectal adenoma located in the proximal colon was more prevalent in the BA-dominant group(BA-CA ≥ 5years) than the CA-dominant group(CA-BA ≥ 5 years)(P = 0.034). When the subjects were categorized into four groups according to MS and age gap between BA and CA, the incidence of colorectal adenoma increased with MS and BA-dominance(P < 0.05).CONCLUSION Measurement of BA may help to assess the risk of colorectal adenoma in screening colonoscopy.展开更多
BACKGROUND Gut tryptophan(Trp)metabolites are produced by microbiota and/or host metabolism.Some of them have been proven to promote or inhibit colorectal cancer(CRC)in vitro and animal models.We hypothesized that the...BACKGROUND Gut tryptophan(Trp)metabolites are produced by microbiota and/or host metabolism.Some of them have been proven to promote or inhibit colorectal cancer(CRC)in vitro and animal models.We hypothesized that there is an alteration of gut Trp metabolism mediated by microbiota and that it might be involved in the pathogenesis of cancer in patients with CRC.AIM To investigate the features of Trp metabolism in CRC and the correlation between fecal Trp metabolites and gut microbiota.METHODS Seventy-nine patients with colorectal neoplastic lesions(33 with colon adenoma and 46 with sporadic CRC)and 38 healthy controls(HCs)meeting the inclusion and exclusion criteria were included in the study.Their demographic and clinical features were collected.Fecal Trp,kynurenine(KYN),and indoles(metabolites of Trp metabolized by gut microbiota)were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry.Gut barrier marker and indoleamine 2,3-dioxygenase 1(IDO1)mRNA were analyzed by quantitative realtime polymerase chain reaction.Zonula occludens-1(ZO-1)protein expression was analyzed by immunohistochemistry.The gut microbiota was detected by 16S ribosomal RNA gene sequencing.Correlations between fecal metabolites and other parameters were examined in all patients.RESULTS The absolute concentration of KYN[1.51(0.70,3.46)nmol/g vs 0.81(0.64,1.57)nmol/g,P=0.036]and the ratio of KYN to Trp[7.39(4.12,11.72)×10^-3 vs 5.23(1.86,7.99)×10^-3,P=0.032]were increased in the feces of patients with CRC compared to HCs,while the indoles to Trp ratio was decreased[1.34(0.70,2.63)vs 2.46(1.25,4.10),P=0.029].The relative ZO-1 mRNA levels in patients with CRC(0.27±0.24)were significantly lower than those in HCs(1.00±0.31)(P<0.001),and the relative IDO1 mRNA levels in patients with CRC[1.65(0.47-2.46)]were increased(P=0.035).IDO1 mRNA levels were positively associated with the KYN/Trp ratio(r=0.327,P=0.003).ZO-1 mRNA and protein levels were positively correlated with the indoles/Trp ratio(P=0.035 and P=0.009,respectively).In addition,the genera Asaccharobacter(Actinobacteria)and Parabacteroides(Bacteroidetes),and members of the phylum Firmicutes(Clostridium XlVb,Fusicatenibacter,Anaerofilum,and Anaerostipes)decreased in CRC and exhibited a positive correlation with indoles in all subjects.CONCLUSION Alteration of fecal Trp metabolism mediated by microbiota is associated with intestinal barrier function and tissue Trp metabolism,and may be involved in the pathogenesis of CRC.展开更多
文摘Current algorithms for screening and surveillance for colon cancer are valuable, but may be limited by the underlying nature of the targeted neoplastic lesions. Although part of the success of adenoma removal relates to interruption of so-called "adenoma-carcinoma sequence", an alternate serrated pathway to colon cancer may pose difficulties with the ultimate results achieved by traditional colonoscopic methods. The endpoint carcinoma in this unique pathway may be derived from a dysplastic serrated adenoma. These tend to be located primarily in the right colon, especially in females, and are frequently associated with co-existent colon cancer. Unfortunately, however, there are few, if any, other identifiable risk factors, including age or family history of colon polyps or colon cancer. Moreover, this alternate serrated pathway may itself also be quite biologically heterogeneous as reflected in sessile serrated adenomas (SSA) with virtually exclusive molecular signatures defined by the presence of either BRAF or KRAS mutations. Screening algorithms in the future may need to be modified and individualized, depending on new information that likely will emerge on the natural history of these biologically heterogeneous lesions that differs from traditional adenomatous polyps.
文摘Texture and color enhancement imaging(TXI)has been developed as a novel image-enhancing endoscopy.However,the effectiveness of TXI detecting adenomas is inferior to narrow band imaging.Thus,future studies will need to focus on investigating the feasibility of such combination in clinical settings in order to provide patients with more accurate diagnoses.
文摘AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or “high-risk” adenomas), and rated each trial’s risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence).CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.
文摘AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.
基金Supported by the Public Health Service grants, No. R01CA-51932 to RMB (National Cancer Institute)Center for Colon Cancer Research grant, No. RR017698 to FGB from National Institutes of Health, Department of Health and Human Services
文摘AIM： Recent laboratory and epidemiological studies suggest that vitamin D is a potential agent for colorectal cancer prevention. Its function is partially mediated by the vitamin D receptor （VDR）. The aim of this study was to investigate whether a novel G （allele ‘U’g〉A （allele ‘u’ polymorphism （Tru9I） in the VDR intron 8 region is associated with risk for colorectal adenoma in a colonoscopy-based case-control study. METHODS： Genotyping for a total of 391 subjects was carried out through PCR and restriction fragment length polymorphism. RESULTS： The frequencies of ‘U’ and ‘u’ alleles were 89.3% and 10.7%, respectively. The ‘Uu’ and ‘uu’ genotypes were associated with decreased risk for adenoma （OR, 0.71; 95%CI, 0.40-1.25）. The inverse association was more pronounced for multiple adenomas and adenomas that were larger had moderate or greater dysplasia, or were sessile： the odds ratios （ORs） were, 0.51 （95%CI, 0.21-1.24）, 0.37 （95%CI, 0.11-1.28）, 0.68 （95%CI, 0.33- 1.41）, and 0.36 （95%CI, 0.13-0.97） respectively. In joint/ combined analyses, inverse associations were more obvious among those who had at least one ‘u’ allele and also were younger （OR, 0.60; 95%CI, 0.26-1.37）, women （OR, 0.38; 95%CI, 0.17-0.88）, did not smoke （OR, 0.39; 95%CI, 0.13-1.23）, or took NSAID （OR, 0.38; 95%CI, 0.12-1.25）, but no evidence existed for interactions with calcium or vitamin D intake.CONCLUSION： Our findings suggest that the VDR TrugI polymorphism may be associated with lower risk for colorectal adenoma, particularly in interaction with various risk factors, but not with calcium or vitamin D.
基金Supported by Grant-in-Aid for Research from the Third-Term Comprehensive Control Research for Cancer Center of the Ministry of Health, Labor and Welfare, JapanGrant from the Ministry of Education, Culture, Sports, Science and Technology, Japan(KIBAN-B)the "Collaborative Development of Innovative Seeds" Grant Program from the Japan Science and Technology Agency
文摘AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.
基金Supported by a grant from the ELAN-Program of the FAUErlangen, Germany, No. 00.05.31.1
文摘AIM: To assess the extent and reasons of non- compliance in surveillance for patients undergoing polypectomy of large (≥ 1 cm) colorectal adenomas. METHODS: Between 1995 and 2002, colorectal adenomas ≥ 1 cm were diagnosed in 210 patients and subsequently documented at the Erlangen Registry of Colorectal Polyps. One hundred and fi fty-eight patients (75.2%) could be contacted by telephone and agreed to be interviewed. Additionally, records were obtained from the treating physicians. RESULTS: Fifty-four out of 158 patients (34.2%) neglected any surveillance. Reasons for non-compliance included lack of knowledge concerning surveillance intervals (45.8%), no symptoms (29.2%), fear of examination (18.8%) or old age/severe illness (6.3%). In a multivariate analysis, the factors including female gender (P = 0.036) and age > 62 years (P = 0.016) proved to be signif icantly associated with non-compliance in surveillance. CONCLUSION: Efforts to increase compliance in surveillance are of utmost importance. This applies particularly to women’s compliance. Effective strategies for avoiding metachronous colorectal adenoma and cancer should focus on both the improvement in awareness and knowledge of patients and information about physicians for surveillance.
文摘Background: It is uncertain that whether smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas, so we peformed the case-control study to explore this issue. Material and Methods: The cases were defined as patients with advanced adenomas and the controls were patients with nonadvanced adenomas. Clinical data were extracted from the hospital information system. Missing data were imputed with the multiple imputation of chained equations method, and the effect of smoking on the risk of advanced adenomas was calculated by binary logistic regression models to obtain odds ratios (ORs) and 95% confidence interval. Results: Current smoking rate in patients with advanced adenomas was significantly higher than that in patients with nonadvanced adenomas (31.6% VS 23.1%), the OR of advanced adenoma for current smoking compared with nonsmoking was 1.54 (1.09, 2.18), P = 0.013, and the weighted ORs ranged from 1.50 (1.01, 2.23) to 1.58 (1.09, 2.30), and the results of sensitivity analyses were still consistent. Conclusion: In adults with Han ethnicity in South China, current smoking is a risk factor of colorectal advanced adenomas compared to nonadvanced adenomas.
基金Supported by the National Natural Science Foundation of China,No.62375202Natural Science Foundation of Tianjin,No.23JCYBJC00950+1 种基金Tianjin Health Science and Technology Project Key Discipline Special,No.TJWJ2022XK034Research Project in Key Areas of Traditional Chinese Medicine in 2024,No.2024022.
文摘BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were evaluated.Clinical data including laboratory results,colonoscopy findings,and pathology reports were collected.Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic regression.The performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve analysis.RESULTS The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin levels.The novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation groups.Calibration curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP.CONCLUSION The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.
基金Jinhua Traditional Chinese Medicine Science and Technology Research Project:Gut Microbiota Distribution Characteristics in Spleen-Deficiency Colorectal Adenoma Patients(No.2023KR04)Jinhua Traditional Chinese Medicine Science and Technology Major Research Project:Clinical Efficacy and Mechanism of Shugan Jianpi Tiaochang Pills in Preventing Postoperative Recurrence of Colorectal Adenomas based on Metabolomics Technology(No.2024ZD03)。
文摘OBJECTIVES:To systematically review the efficacy and safety of Jianpi formulas(健脾剂)in reducing the recurrence of colorectal adenoma(CRA)after polypectomy.METHODS:Randomized controlled trials(RCTs)investigating Jianpi formulas for CRA post-polypectomy were systematically retrieved from eight electronic databases.The quality of the methodology was assessed using the Cochrane collaboration tool.The Grades of Recommendations Assessment Development and Evaluation(GRADE)approach was employed for evidence assessment.Statistical analyses were conducted using Statistics and Data Analysis(STATA)17(StataCorp(College Station,TX,USA)and Review Manager(RevMan)5.4(The Cochrane Collaboration(London,UK).RESULTS:The Meta-analysis,encompassing 18 RCTs with 1838 patients,revealed that Jianpi formulas significantly outperformed postoperative routine treatment.It demonstrated a reduction in the half-year recurrence rate[relative risk(RR)=0.41,95%confidence interval(CI)=0.33-0.49,Z=9.08,P<0.00001],the oneyear recurrence rate[RR=0.58,95%CI=0.49-0.69,Z=6.12,P<0.00001],and an enhancement in the clinical effective rate[RR=1.27,95%CI=1.19-1.36,Z=7.06,P<0.00001].The half-year recurrence rate and the clinical effective rate were medium-quality evidence.The one-year recurrence rate was low-quality evidence.Additionally,Jianpi formulas appear to be safe and do not increase adverse reactions compared to postoperative routine treatment alone.CONCLUSION:Jianpi formulas exhibit efficacy in reducing postoperative half-year and one-year recurrence rates while improving the clinical effective rate after polypectomy for CRA.
基金Akdeniz University Scientific Research Foundation,Turkey,No.2017040103020.
文摘BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs,including the colon.Accordingly,studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression.Although Numb,Itch,and seven in absentia homolog-1(Siah-1)have been shown to contribute to the regulation of Notch signaling,their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date.AIM To evaluate Numb,Itch,and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior.METHODS Expression of Notch-1,Numb,Itch,and Siah-1 was investigated in 50 colorectal carcinomas,30 adenomas,and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(PCR)analyses.RESULTS In contrast to Notch-1,which is expressed at higher levels in tumor tissues and adenomas,expression of Numb,Itch,and Siah-1 was stronger and more frequent in normal mucosa(P<0.01).There was a positive correlation between Notch-1 expression and high histological grade,the presence of lymph node metastasis,and advanced-stage tumors,whereas expression of Numb,Itch,and Siah-1 was absent or reduced in tumors with these clinicopathological parameters(P<0.05).In survival analysis,expression of Notch was related to poor prognosis but that of Numb,Itch,and Siah-1 correlated with improved survival(P<0.05).Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis(P<0.05).CONCLUSION Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb,Itch,and Siah-1 expression is associated with carcinogenesis.Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma(CRC)progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.
基金Supported in part by Natural Science Foundation of Hubei Province (No. 302-131703)
文摘Objective:The aim of this study was to investigate lipid disorders and lipid peroxidation associated with the malignant transformation of colorectal adenoma.Methods:Analyses were based on data from 100 subjects with histologically confirmed adenomas(cases) and 50 adenoma-free control subjects,all of whom had colonoscopy.The subjects were divided into two groups:those with no adenoma and those with adenoma.According to subsite of adenomas the subjects with adenoma were divided into group of distal adenoma and group of proximal adenoma.According to histology of adenomas the subjects with adenoma were divided into group of villiform adenoma and group of tubular + tubulo-villous adenoma.Among the groups,the serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),lowdensity lipoprotein cholesterol(LDL-C),and lipid peroxidation product malondialdehyde(MDA) were compared in all the patients.Results:Plasma total cholesterol and MDA level in group of adenomas were significantly higher than that in group of control subjects,but plasma HDL-C level was low in group of adenomas(P<0.05).Plasma total cholesterol and MDA levels were positively related to distal and villiform adenomas(P<0.05).Conclusion:The findings suggest that altered lipid metabolism may be differentially associated with colorectal adenomas.
基金Supported by Sao Paulo Research Foundation(FAPESP),No.2012/15036-8National Council for Scientific and Technological Development(CNPq),No.474.776/2013-1+2 种基金the Sao Paulo Research Foundation(FAPESP,NO.2015/21464-0)for the support for English revisionthe Coordination for the Improvement of Higher Education Personnel(CAPES)for the doctoral scholarshipthe National Council for Scientific and Technological Development(CNPq,NO.310120/2015-2)for the productivity research scholarship
文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.
文摘Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas.Among crucial roles of epigenetic alterations,gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms.Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes.Each epigenotype cooperates with specific genetic alterations,suggesting that they represent different molecular carcinogenic pathways.Precursor lesions of CRC,such as conventional and serrated adenomas,already show similar methylation accumulation to CRC,and can therefore be classified into those epigenotypes of CRC.In addition,specific DNA methylation already occurs in the normal colonic mucosa,which might be utilized for prediction of the personal CRC risk.DNA methylation is suggested to occur at an earlier stage than carcinoma formation,and may predict the molecular basis for future development of CRC.Here,we review DNA methylation and CRC classification,and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis,prediction of the prognosis and the response to therapy of CRC.
文摘Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy.Since CRC develops slowly from precancerous lesions,early detection can reduce both the incidence and mortality of the disease.Fecal occult blood test is a widely used non-invasive screening tool for CRC.Although fecal occult blood test is simple and cost-effective in screening CRC,there is room for improvement in terms of the accuracy of the test.Genetic dysregulations have been found to play an important role in CRC development.With better understanding of the molecular basis of CRC,there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC.In this review,the molecular basis of CRC development,the characteristics and applications of different non-invasive molecular biomarkers,as well as the technologies available for the detection were discussed.This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state,colorectal adenoma.
基金Supported by The Capital Health Development Special Scientific Research Projects,No.2014-2-2154National Natural Science Foundation of China,No.81471761 and No.81501568
文摘AIM The purpose of this study was to evaluate the diagnostic value of trefoil factor family 3(TFF3) for the early detection of colorectal cancer(CC). METHODS Serum TFF3 and carcino-embryonic antigen(CEA) were detected in 527 individuals, including 115 healthy control(HC), 198 colorectal adenoma(CA), and 214 CC individuals in the training group. RESULTS Serum TFF3 showed no significant correlation with age, gender, or tumor location but showed significant correlation with the tumor stage. Serum TFF3 in the CC group was significantly higher than in the HC or CA group. The AUC values of TFF3 for discriminating between HC and CC and between CA and CC were 0.930(0.903, 0.958) and 0.834(0.796, 0.873). A multivariate model combining TFF3 and CEA was built. Compared to TFF3 or CEA alone, the multivariate model showed significant improvement(P < 0.001). For discriminating between HC and CC, HC and early stage CC, HC and advanced stage CC, CA and CC, CA and early stage CC, and CA and advanced stage CC in the training group, the sensitivities were 92.99%, 91.46%, 93.18%, 73.83%, 76.83%, and 81.82%, and the specificities were 91.30%, 91.30%, 93.91%, 88.38%, 77.27%, and 88.38%, respectively. After validation, the sensitivities were 89.39%, 85.71%, 90.79%, 72.73%, 71.43%, and 78.95%, and the specificities were 87.85%, 87.85%, 2.52%, 87.85%, 80.77%, and 87.50%, respectively. CONCLUSION The multivariate diagnostic model that included TFF3 and CEA showed significant improvement over the conventional biomarker CEA and might provide a potential method for the early detection of CC.
文摘To perform a meta-analysis of observational studies on inflammatory markers levels and occurrence of colorectal adenoma.METHODSPubMed and EMBASE databases were searched until March 2016 for the articles reporting on the circulating levels of inflammatory markers,including:C-reactive protein(CRP),interleukin-6(IL-6),and tumor necros is factor-alpha(TNF-α)and risk of colorectal adenoma.Random-effects models were used to calculate summary odds ratios(ORs)with 95%CIs for the highest vs lowest category of exposure.Heterogeneity was assessed by using the Q test and I<sup>2</sup>statistic.Subgroup analyses were also performed to test for potential source of heterogeneity.RESULTSA total of 14 case-control studies were included.Ten studies on CRP including a total of 3350 cases and 4168 controls showed non-significant summary(OR=1.23,95%CI:0.98-1.54;I<sup>2</sup>=54%,P<sub>heterogeneity</sub>=0.01)in the general analysis,but significant increased odds when considering only advanced adenoma(OR=1.59,95%CI:1.09-2.32;I<sup>2</sup>=44%,P<sub>heterogeneity</sub>=0.15).Subgroup and stratified analyses revealed a potential influence of smoking status and aspirin use on the association between CRP levels and colorectal adenoma.Five studies examined the association between circulating levels of TNF-αand colorectal adenoma risk,including a total of 1,568 cases and 2,832 controls.The summary OR for the highest vs the lowest category of exposure was 1.00(95%CI:0.77-1.29).The relationship between circulating IL-6 levels and colorectal adenoma risk was investigated in 7 studies including a total of 1936 cases and 3611 controls.The summary OR for the highest vs the lowest category of exposure was 1.19(95%CI:0.92-1.55).CONCLUSIONSummary of current evidence suggests a positive association of CRP levels and advanced colorectal adenoma risk.The role of potential confounding factors should be further evaluated.
文摘AIM To investigate the clinical utility of biological age(BA) measurement in screening colonoscopy for the detection of colorectal adenomas in the average-risk population.METHODS A consecutive series of asymptomatic subjects aged ≥ 30 years who underwent colonoscopy in routine check-ups were enrolled. Colorectal adenoma was classified according to size, number, and location. BAs were calculated using the MEDIAGETM Biological Age Measurement System.RESULTS A total of 2696 subjects were investigated(1876 men and 820 women). The mean chronological age(CA) was 46.0 years and the mean BA was 44.7 years. Metabolic syndrome(MS) was diagnosed in 218 subjects(8.1%). The prevalence of overall colorectal adenoma was 23.1%(622/2,696). When the subjects were divided into four groups based on BA(≤ 39 years; 40-49 years; 50-59 years; ≥ 60 years), the prevalence of colorectal adenoma was increased as BA increased(P < 0.001). Colorectal adenoma located in the proximal colon was more prevalent in the BA-dominant group(BA-CA ≥ 5years) than the CA-dominant group(CA-BA ≥ 5 years)(P = 0.034). When the subjects were categorized into four groups according to MS and age gap between BA and CA, the incidence of colorectal adenoma increased with MS and BA-dominance(P < 0.05).CONCLUSION Measurement of BA may help to assess the risk of colorectal adenoma in screening colonoscopy.
基金Supported by National Key Research and Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND Gut tryptophan(Trp)metabolites are produced by microbiota and/or host metabolism.Some of them have been proven to promote or inhibit colorectal cancer(CRC)in vitro and animal models.We hypothesized that there is an alteration of gut Trp metabolism mediated by microbiota and that it might be involved in the pathogenesis of cancer in patients with CRC.AIM To investigate the features of Trp metabolism in CRC and the correlation between fecal Trp metabolites and gut microbiota.METHODS Seventy-nine patients with colorectal neoplastic lesions(33 with colon adenoma and 46 with sporadic CRC)and 38 healthy controls(HCs)meeting the inclusion and exclusion criteria were included in the study.Their demographic and clinical features were collected.Fecal Trp,kynurenine(KYN),and indoles(metabolites of Trp metabolized by gut microbiota)were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry.Gut barrier marker and indoleamine 2,3-dioxygenase 1(IDO1)mRNA were analyzed by quantitative realtime polymerase chain reaction.Zonula occludens-1(ZO-1)protein expression was analyzed by immunohistochemistry.The gut microbiota was detected by 16S ribosomal RNA gene sequencing.Correlations between fecal metabolites and other parameters were examined in all patients.RESULTS The absolute concentration of KYN[1.51(0.70,3.46)nmol/g vs 0.81(0.64,1.57)nmol/g,P=0.036]and the ratio of KYN to Trp[7.39(4.12,11.72)×10^-3 vs 5.23(1.86,7.99)×10^-3,P=0.032]were increased in the feces of patients with CRC compared to HCs,while the indoles to Trp ratio was decreased[1.34(0.70,2.63)vs 2.46(1.25,4.10),P=0.029].The relative ZO-1 mRNA levels in patients with CRC(0.27±0.24)were significantly lower than those in HCs(1.00±0.31)(P<0.001),and the relative IDO1 mRNA levels in patients with CRC[1.65(0.47-2.46)]were increased(P=0.035).IDO1 mRNA levels were positively associated with the KYN/Trp ratio(r=0.327,P=0.003).ZO-1 mRNA and protein levels were positively correlated with the indoles/Trp ratio(P=0.035 and P=0.009,respectively).In addition,the genera Asaccharobacter(Actinobacteria)and Parabacteroides(Bacteroidetes),and members of the phylum Firmicutes(Clostridium XlVb,Fusicatenibacter,Anaerofilum,and Anaerostipes)decreased in CRC and exhibited a positive correlation with indoles in all subjects.CONCLUSION Alteration of fecal Trp metabolism mediated by microbiota is associated with intestinal barrier function and tissue Trp metabolism,and may be involved in the pathogenesis of CRC.
