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• W4377021568 abstract "Abstract Background: Lynch syndrome screening should include MLH1 promoter methylation detection in patients with deficiency of MLH1 (dMLH1) in colorectal cancer, but there is still no consensus on the CpG detection sites. The aim of this study is to analyze the correlation between the specific CpG sites of MLH1 promoter and dMLH1 in a large sample, and to find the best detection region. Methods: Immunohistochemistry (IHC) was used to detect DNA mismatch repair (MMR) protein in patients with colorectal cancer (CRC), and bisulfite sequencing PCR (BSP) was used to detect MLH1 promoter methylation. MLH1 promoter was divided into 5 regions: region A (-755 to -574, relative to the start codon), region B (-597 to -393), region C (-420 to -188), region D (-286 to -53) and region E (-73 to +86), which were tested respectively. The correlation between methylation in each region and MLH1 expression was analyzed. The sample size was gradually expanded to 626 cases for testing the highest correlation region. Subsequently, the correlation between MLH1 promoter methylation and clinical parameters was analyzed, and a nomogram model for the prediction of MLH1 promoter methylation was established. Survival analysis was performed to analyze the influence of MLH1 promoter methylation on the prognosis of CRC. Results: The p values of correlation between methylation in five regions( regions A, B, C, D, and E) and MLH1 protein expression were 0.070, 0.070, 0.005, 0.002 and 0.002, respectively. Regions D and E were consistent. In the cohort of 626 cases, methylation in region E was significantly correlated with the female, family history, mutant BRAF V600E , dMLH1 and deficiency of PMS2 (dPMS2). The consistency of the nomogram model we established to predict MLH1 methylation and BSP was 78.6%. And the sensitivity and specificity of this nomogram model were 97.5% and 72.8%, respectively. In this article, we found that MLH1 promoter methylation had no significant effect on the prognosis of CRC. Conclusions: In colorectal cancer, the CpG sites in the region E of the MLH1 promoter are recommended to determine the status of MLH1 methylation. The nomogram model of MLH1 promoter methylation is valuable and reliable for predicting MLH1 methylation status." @default.
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• W4377021568 date "2023-05-18" @default.
• W4377021568 modified "2023-09-29" @default.
• W4377021568 title "A recommended testing region in MLH1 promoter for methylation detection in colorectal cancer patients" @default.
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• W4377021568 doi "https://doi.org/10.21203/rs.3.rs-2885404/v1" @default.
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