Testing region selection and prognostic analysis of MLH1 promoter methylation in colorectal cancer in China
Xiaoli Tan1
Yongzhen Fang2
Xinjuan Fan1
Weihao Deng1
Jinglin Huang1
Yacheng Cai1
Jiaxin Zou3
Zhiting Chen1
Hanjie Lin1
Liang Xu1
Guannan Wang2
Huanmiao Zhan1
Shuhui Huang1
Xinhui Fu4
1.Department of Pathology,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China2.Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China3.Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China;Department of General Surgery,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China4.Department of Pathology,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China;Biomedical Innovation Center,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China
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 immu-nohistochemistry(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 methyla-tion was more common in patients who were aged≥50 years,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.
机标关键词：analysisregioncancerchinacolorectalmethylationprognosticpromoter
论文发表日期：2024-06-30
在线出版日期：2026-07-17（本平台首次上网日期，不代表文献的发表时间）
页数：9( 251-259 )
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