MLH1 Promoter Methylation and Prediction/Prognosis of Gastric Cancer: A Systematic Review and Meta and Bioinformatic Analysis

Abstract

Background: The promoter methylation of MLH1 gene and gastric cancer (GC)has been investigated previously. To get a more credible conclusion, we performed a systematic review and meta and bioinformatic analysis to clarify the role of MLH1 methylation in the prediction and prognosis of GC.Methods: Eligible studies were targeted after searching the PubMed, Web of Science, Embase, BIOSIS, CNKI and Wanfang Data to collect the information of MLH1 methylation and GC. The link strength between the two was estimated by odds ratio with its 95% confidence interval. The Newcastle-Ottawa scale was used for quantity assessment. Subgroup and sensitivity analysis were conducted to explore sources of heterogeneity. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed for bioinformatics analysis on the correlation between MLH1 methylation and GC risk, clinicopathological behavior as well as prognosis.Results: 2365 GC and 1563 controls were included in the meta-analysis. The pooled OR of MLH1 methylation in GC was 4.895 (95% CI: 3.149-7.611, P<0.001), which considerably associated with increased GC risk. No significant difference was found in relation to Lauren classification, tumor invasion, lymph node/distant metastasis and tumor stage in GC. Analysis based on GEO and TCGA showed that high MLH1 methylation enhanced GC risk but might not related with GC clinicopathological features and prognosis.Conclusion: MLH1 methylation is an alive biomarker for the prediction of GC and it might not affect GC behavior. Further study could be conducted to verify the impact of MLH1 methylation on GC prognosis.

Focusing on the Abnormal Events of NPC1, NPC2, and NPC1L1 in Pan-Cancer and Further Constructing LUAD and KICH Prediction Models

“…26 Furthermore, the amount of DNA methylation in NPCs and its link to tumor growth were studied at the epigenetic level. Cervical cancer, 27 colorectal cancer, 28 gastric cancer, 29,30 and pancreatic cancer, 31 among others, have been identified to contain particular genetic changes, and this signature is employed as a predictive marker for cancer. According to our findings, the difference in NPCs methylation levels in most malignancies can predict the prognosis of cancer patients.…”

Development of a liquid biopsy based purely quantitative digital droplet PCR assay for detection of MLH1 promoter methylation in colorectal cancer patients

“…The tissue based pooled frequency of MLH1 promoter methylation in CRC is reported as ~ 18% in sporadic CRC [ 34 , 35 ]. DNA methylation of MLH1 has been found in more than 80% of sporadic CRC with MSI and predict the mutation load.…”

Development of a Liquid Biopsy Based Purely Quantitative Digital Droplet PCR Assay for Detection of MLH1 Promoter Methylation in Colorectal Cancer Patients

“…The tissue based pooled frequency of MLH1 promoter methylation in CRC is reported as ~18% in sporadic CRC [29,30]. DNA methylation of MLH1 has been found in more than 80% of sporadic CRC with MSI and predict the mutation load.…”