BACKGROUND Hereditary non-polyposis colon cancer is a dominantly inherited syndrome of colorectal cancer(CRC),with heightened risk for younger population.Previous studies link its susceptibility to the DNA sequence po...BACKGROUND Hereditary non-polyposis colon cancer is a dominantly inherited syndrome of colorectal cancer(CRC),with heightened risk for younger population.Previous studies link its susceptibility to the DNA sequence polymorphism along with Amsterdam and Bethesda criteria.However,those fail in term of applicability.AIM To determine a clear cut-off of MSH2 gene expression for CRC heredity grouping factor.Further,the study also aims to examine the association of risk factors to the CRC heredity.METHODS The cross-sectional study observed 71 respondents from May 2018 to December 2019 in determining the CRC hereditary status through MSH2 mRNA expression using reverse transcription-polymerase chain reaction and the disease’s risk factors.Data were analyzed through Chi-Square,Fischer exact,t-test,Mann-Whitney,and multiple logistics.RESULTS There are significant differences of MSH2 within CRC group among tissue and blood;yet,negative for significance between groups.Through the blood gene expression fifth percentile,the hereditary CRC cut-off is 11059 fc,dividing the 40 CRC respondents to 32.5%with hereditary CRC.Significant risk factors include age,family history,and staging.Nonetheless,after multivariate control,age is just a confounder.Further,the study develops a probability equation with area under the curve 82.2%.CONCLUSION Numerous factors have significant relations to heredity of CRC patients.However,true important factors are staging and family history,while age and others are confounders.The study also established a definite cut-off point for heredity CRC based on mRNA MSH2 expression,11059 fc.These findings shall act as concrete foundations on further risk factors and/or genetical CRC future studies.展开更多
BACKGROUND The development of colorectal cancer(CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes.In the process of DNA replication, base mismat...BACKGROUND The development of colorectal cancer(CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes.In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes(MMR),among which MLH1 and MSH2 are the most important.Recently, numerous studies indicated that MLH1/MSH2 phenotype is associated with CRC.We wanted to elucidate the role of MLH1/MSH2 in the prediction and prognosis of CRC through long-term clinical observation.AIM To evaluate the prognostic and predictive significance of MLH1/MSH2 in patients with stage Ⅱ-Ⅲ CRC using immunohistochemical analysis and GeneScan.METHODS Specimens from 681 patients with CRC(395 stage Ⅱ and 286 stage Ⅲ, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested.Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis.RESULTS Five hundred and fifty(80.76%) patients were MLH1/MSH2 positive and 131(19.24%) were negative by immunohistochemistry.MLH1/MSH2-positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production(P < 0.05).Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin.MLH1/MSH2-negative patients had a more favorable OS than MLH1/MSH2-positive patients(P < 0.001).Univariate and multivariate analyses demonstrated MLH1/MSH2 expression as an independent prognostic and predictive factor for stage Ⅱ/Ⅲ CRC.MLH1/MSH2 expression was a strong prognostic factor in all patients [P < 0.001, hazard ratio(HR) = 4.064,95%CI: 2.241–7.369].Adjuvant chemotherapy had a greater correlation with survival advantage in MLH1/MSH2-negative patients with stage Ⅲ disease(P <0.001, HR = 7.660, 95%CI: 2.974–15.883).However, patients with stage Ⅱ disease or MLH1/MSH2-positive patients with stage Ⅲ disease did not benefit from adjuvant chemotherapy.GeneScan analysis demonstrated that among 133 patients, 105(78.95%) were microsatellite stable, and 28(21.05%) had microsatellite instability(MSI), including 18(13.53%) with high MSI and 10(7.52%) with low MSI.This is consistent with the immunohistochemical results.CONCLUSION MLH1/MSH2 phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC.MLH1/MSH2 is an independent prognostic and predictive factor for outcome of stage Ⅱ-Ⅲ CRC.展开更多
Objective: To investigate the expression of fragilehistidine triad (FHIT) gene and its correlation withclinicopathological features and correlation with mismatchrepair protein (mainly MLH1 and MSH2) in humansporadic c...Objective: To investigate the expression of fragilehistidine triad (FHIT) gene and its correlation withclinicopathological features and correlation with mismatchrepair protein (mainly MLH1 and MSH2) in humansporadic colorectal carcinoma (SCC). Methods:Immunohistochemistry SP method was used to determinethe expression of FHIT, MLH1 and MSH2 protein insurgically resected specimens of 84 human SCC. Results:The positive rates of FHIT, MLH1 and MSH2 proteinexpression were 48.81%, 92.86% and 100% respectively.Loss or reduced expression of FHIT protein was not related with tumors clinicopathological features such as age, gender, tumors site and histological type (P>0.05), but wascorrelated with tumors invade depth, degree of thedifferentiation, Ducks?stage and metastasis (P<0.05). There was no relationship between FHIT gene expression andMLH1 protein (r=0.0991, P>0.05) and MSH2 protein(r=0.0000, P=l.00) expression in human SCC. Conclusion:Absent or reduction of FHIT gene expression consists ofhigh proportion and is a frequent event in SCC. FHIT gene is involved in the development and progression of humanSCC and may be a candidate tumors suppressor gene. The relationship between alteration of FHIT gene expression and mismatch repair protein (mainly MLH1 and MSH2)deserved further study in human SCC.展开更多
采用高传能线密度(LET)重离子辐照人胃癌SGC7901细胞,应用流式细胞技术、蛋白质印迹法(Western blot)及反转录聚合酶链式反应(RT-PCR)观察重离子诱导人胃癌SGC7901细胞周期、凋亡和MSH2表达状况。结果表明:与对照组相比,SGC7901细胞在...采用高传能线密度(LET)重离子辐照人胃癌SGC7901细胞,应用流式细胞技术、蛋白质印迹法(Western blot)及反转录聚合酶链式反应(RT-PCR)观察重离子诱导人胃癌SGC7901细胞周期、凋亡和MSH2表达状况。结果表明:与对照组相比,SGC7901细胞在辐射后72 h G2/M期所占细胞比率(33.26±0.08)和凋亡率(24.16±0.64)均达到峰值,且呈时间依赖性增加;经重离子照射后,DNA错配修复基因MSH2 m RNA和蛋白表达水平在6 h最高。结果提示:重离子在体外诱导SGC7901细胞周期阻滞和凋亡,且具有显著的时间依赖性效应;重离子在一定剂量和时间下,诱导了SGC7901细胞MSH2基因表达。DNA错配修复基因MSH2可能参与了重离子辐照诱导胃癌细胞DNA损伤的修复应答。展开更多
文摘BACKGROUND Hereditary non-polyposis colon cancer is a dominantly inherited syndrome of colorectal cancer(CRC),with heightened risk for younger population.Previous studies link its susceptibility to the DNA sequence polymorphism along with Amsterdam and Bethesda criteria.However,those fail in term of applicability.AIM To determine a clear cut-off of MSH2 gene expression for CRC heredity grouping factor.Further,the study also aims to examine the association of risk factors to the CRC heredity.METHODS The cross-sectional study observed 71 respondents from May 2018 to December 2019 in determining the CRC hereditary status through MSH2 mRNA expression using reverse transcription-polymerase chain reaction and the disease’s risk factors.Data were analyzed through Chi-Square,Fischer exact,t-test,Mann-Whitney,and multiple logistics.RESULTS There are significant differences of MSH2 within CRC group among tissue and blood;yet,negative for significance between groups.Through the blood gene expression fifth percentile,the hereditary CRC cut-off is 11059 fc,dividing the 40 CRC respondents to 32.5%with hereditary CRC.Significant risk factors include age,family history,and staging.Nonetheless,after multivariate control,age is just a confounder.Further,the study develops a probability equation with area under the curve 82.2%.CONCLUSION Numerous factors have significant relations to heredity of CRC patients.However,true important factors are staging and family history,while age and others are confounders.The study also established a definite cut-off point for heredity CRC based on mRNA MSH2 expression,11059 fc.These findings shall act as concrete foundations on further risk factors and/or genetical CRC future studies.
基金Supported by Medical Science and Technology Development Foundation,Nanjing Department of Health,No.YKK14140(to ShuiMing Wang)and No.ZKX15040(to Bin Jiang)Project of Administration of Traditional Chinese Medicine of Jiangsu Province of China,No.LZ11101(to Zhi-Ming Fang)
文摘BACKGROUND The development of colorectal cancer(CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes.In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes(MMR),among which MLH1 and MSH2 are the most important.Recently, numerous studies indicated that MLH1/MSH2 phenotype is associated with CRC.We wanted to elucidate the role of MLH1/MSH2 in the prediction and prognosis of CRC through long-term clinical observation.AIM To evaluate the prognostic and predictive significance of MLH1/MSH2 in patients with stage Ⅱ-Ⅲ CRC using immunohistochemical analysis and GeneScan.METHODS Specimens from 681 patients with CRC(395 stage Ⅱ and 286 stage Ⅲ, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested.Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis.RESULTS Five hundred and fifty(80.76%) patients were MLH1/MSH2 positive and 131(19.24%) were negative by immunohistochemistry.MLH1/MSH2-positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production(P < 0.05).Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin.MLH1/MSH2-negative patients had a more favorable OS than MLH1/MSH2-positive patients(P < 0.001).Univariate and multivariate analyses demonstrated MLH1/MSH2 expression as an independent prognostic and predictive factor for stage Ⅱ/Ⅲ CRC.MLH1/MSH2 expression was a strong prognostic factor in all patients [P < 0.001, hazard ratio(HR) = 4.064,95%CI: 2.241–7.369].Adjuvant chemotherapy had a greater correlation with survival advantage in MLH1/MSH2-negative patients with stage Ⅲ disease(P <0.001, HR = 7.660, 95%CI: 2.974–15.883).However, patients with stage Ⅱ disease or MLH1/MSH2-positive patients with stage Ⅲ disease did not benefit from adjuvant chemotherapy.GeneScan analysis demonstrated that among 133 patients, 105(78.95%) were microsatellite stable, and 28(21.05%) had microsatellite instability(MSI), including 18(13.53%) with high MSI and 10(7.52%) with low MSI.This is consistent with the immunohistochemical results.CONCLUSION MLH1/MSH2 phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC.MLH1/MSH2 is an independent prognostic and predictive factor for outcome of stage Ⅱ-Ⅲ CRC.
文摘Objective: To investigate the expression of fragilehistidine triad (FHIT) gene and its correlation withclinicopathological features and correlation with mismatchrepair protein (mainly MLH1 and MSH2) in humansporadic colorectal carcinoma (SCC). Methods:Immunohistochemistry SP method was used to determinethe expression of FHIT, MLH1 and MSH2 protein insurgically resected specimens of 84 human SCC. Results:The positive rates of FHIT, MLH1 and MSH2 proteinexpression were 48.81%, 92.86% and 100% respectively.Loss or reduced expression of FHIT protein was not related with tumors clinicopathological features such as age, gender, tumors site and histological type (P>0.05), but wascorrelated with tumors invade depth, degree of thedifferentiation, Ducks?stage and metastasis (P<0.05). There was no relationship between FHIT gene expression andMLH1 protein (r=0.0991, P>0.05) and MSH2 protein(r=0.0000, P=l.00) expression in human SCC. Conclusion:Absent or reduction of FHIT gene expression consists ofhigh proportion and is a frequent event in SCC. FHIT gene is involved in the development and progression of humanSCC and may be a candidate tumors suppressor gene. The relationship between alteration of FHIT gene expression and mismatch repair protein (mainly MLH1 and MSH2)deserved further study in human SCC.
文摘采用高传能线密度(LET)重离子辐照人胃癌SGC7901细胞,应用流式细胞技术、蛋白质印迹法(Western blot)及反转录聚合酶链式反应(RT-PCR)观察重离子诱导人胃癌SGC7901细胞周期、凋亡和MSH2表达状况。结果表明:与对照组相比,SGC7901细胞在辐射后72 h G2/M期所占细胞比率(33.26±0.08)和凋亡率(24.16±0.64)均达到峰值,且呈时间依赖性增加;经重离子照射后,DNA错配修复基因MSH2 m RNA和蛋白表达水平在6 h最高。结果提示:重离子在体外诱导SGC7901细胞周期阻滞和凋亡,且具有显著的时间依赖性效应;重离子在一定剂量和时间下,诱导了SGC7901细胞MSH2基因表达。DNA错配修复基因MSH2可能参与了重离子辐照诱导胃癌细胞DNA损伤的修复应答。
