The prognostic and immunomodulatory role of the MMR system in patients with stomach adenocarcinoma.

The mismatch repair (MMR) system plays a crucial role in the maintenance of DNA replication fidelity and genomic stability. The clinical value of the MMR molecular marker as an immunotherapy for advanced solid tumors has been documented. However, this therapy is not effective in some patients. This study aimed to develop an MMR-related molecular prognostic model for identifying appropriate populations of stomach adenocarcinoma (STAD) for better treatment outcome. The MMR genes expression data were downloaded from TCGA and CCLE databases. The expression of four MMR genes, construction of a prognostic risk model, and assessment of immune infiltration in STAD were performed using Xiantao online tool. GEPIA2 was used to explore the association of MMR genes expression with clinical stage and overall survival. The frequency and prognostic value of MMR genes in STAD were conducted on the cBioPortal. The MLH1 co-expression network was established based on the LinkedOmics database. This study found that the expression of MSH2, MSH6 and PMS2 was up-regulated in STAD tissues. Moreover, differential MMR genetic expression levels were not significantly correlated with the clinical stages of STAD. Besides, no significant difference in PFS or OS was observed in STAD patients with or without MMR genetic alteration. Moreover, MLH1 and MSH2 were used to establish a prognostic risk model. The immune infiltration levels of most immune cells were upregulated in the high-risk group with elevated expression of PDCD1 and low TMB score. Finally, we found that MLH1 was an independent predictor of STAD prognosis among the four MMR genes. An MMR-related prognostic model for STAD was constructed based on genes. This model provides a new therapeutic concept for the diagnosis and treatment of STAD.