Glutathione Reductase change the tumor immune microenvironment and prognosis of colon cancer：A study based on proteomic analysis

Abstract Background Colonic malignant tumor cells can cause metabolic changes in the harsh microenvironment. Glutathione reductase (GSR) plays a key role in anti-oxidative stress in tumor cells, but its specific mechanism remains unclear. Therefore, the objective of this study was to investigate the prognostic value of GSR in patients with colon cancer and its effect on tumor microenvironment. Methods Differential proteins of colon cancer and normal intestinal tissues were obtained by proteomic differential analysis, and key proteins in metabolic pathways were identified by enrichment analysis and protein-protein interaction network (PPI) analysis. Survival analysis, immune infiltration analysis and clinical information correlation analysis were performed. Results A total of 1209 differentially expressed proteins were identified in 10 colon cancer samples. GO and KEGG enrichment analysis showed that differential proteins were significantly enriched in metabolic pathways, with 144 enriched genes (p < 0.05). PPI analysis showed that ADH1A, ADH1B, ADH1C, ADH5, ALDH18A1, ALDH3A1, GSTA1, GSTA2, HPGDS and GSR were the key proteins in the differential proteins metabolic pathway of colon cancer. GEPIA2 survival analysis showed that GSR significantly affected overall survival of colon cancer patients (p = 0.0017, HR = 0.45). Timer and TISIDB database analysis showed that the expression of GSR in colon cancer can significantly affect the level of immune cell infiltration. UALCAN database analysis showed that GSR expression predicted better N stage, overall stage and lower TP53 mutation rate of colon cancer (p < 0.05). The results of HPA database analysis suggested that GSR was mainly expressed in the cytoplasm and nuclear membrane of colonic malignant tumor cells. Conclusions Our study found that GSR plays an important role in the metabolic pathway of colon cancer and affects the prognosis of patients with statistical significance. GSR significantly affects the tumor immune microenvironment, clinical stage and TP53 mutation rate of colonic malignancies. This study provides some basis for the mechanism research and treatment of colon malignancy.