Testing region selection and prognostic analysis of MLH1 promoter methylation in colorectal cancer in China  

作　　者：Xiaoli Tan Yongzhen Fang Xinjuan Fan Weihao Deng Jinglin Huang Yacheng Cai Jiaxin Zou Zhiting Chen Hanjie Lin Liang Xu Guannan Wang Huanmiao Zhan Shuhui Huang Xinhui Fu 

机构地区：[1]Department of Pathology,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China [2]Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China [3]Department of General Surgery,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China [4]Biomedical Innovation Center,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China

出　　处：《Gastroenterology Report》2024年第1期120-128,共9页胃肠病学报道(英文)

基　　金：supported by the National Natural Science Foundation of China[81971999 to X.F.];Science and Technology Achievements Transformation Project of Sun Yat-sen University[88000-18843232 to X.F.];Young Teacher Training Program of Sun Yat-sen University[14YKPY31 to X.F.];China Scholarship Council[201706385049 to X.F.];the program of Guangdong Provincial Clinical Research Center for Digestive Disease[2020B1111170004];National Key Clinical Discipline.

摘　　要：Background:MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome(LS)in patients with MLH1-deficient colorectal cancer(CRC).The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation.Methods:A total of 580 CRC cases were included.The DNA mismatch repair(MMR)protein expression was assessed by using immunohistochemistry(IHC).The methylation status of the Regions A,B,C,D,and E in the MLH1 promoter was tested by using bisulfite sequencing PCR.The specificities of the five regions were calculated.Associations between MLH1 methylation and clinicopathologic characteristics were evaluated.Kaplan-Meier analyses for overall survival(OS)were carried out.Results:In 580 CRC cases,the specificities of the methylation test in Regions D and E were both 97.8%.In the MLH1-deficient CRCs,the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6%and 14.6%,respectively;BRAFV600E mutation occurred in 27.7%of patients with MLH1-methylated CRC.In the MMR-deficient patients,compared with MLH1 unmethylation,MLH1 methylation was more common in patients who were aged≥50years,female,had no family history of LS-related tumors,and had tumors located at the right colon.In the MMR-deficient patients,the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors(P=0.047).Conclusions:Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC.In MMR-deficient patients,the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.

关 键 词：CRC MLH1 deficiency MLH1 promoter methylation overall survival 

分 类 号：R735.34[医药卫生—肿瘤]