Comprehensive analysis of the correlation between GSTM1 and tumor immunity in colon cancer

Abstract

Glutathione S-transferase mu 1 (GSTM1) is one of the major glutathione conjugation enzymes. Its expression and activity have been suggested to correlate with the occurrence of colon cancer; however, the role of GSTM1 in tumor immunity remains unclear. Relevant data downloaded from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) was used to perform a multi-dimensional expression analysis of GSTM1 in colon adenocarcinoma (COAD). The correlation between GSTM1 and tumor immunity was analyzed with multiple online tools. Then protein-protein interaction (PPI) network and functional enrichment analyses of GSTM1-associated immunomodulators were performed. Further, we developed the Cox regression model based on the GSTM1-related immunomodulators. Finally, a GSTM1-based clinical nomogram and a calibration curve was established to predict the probability and accuracy of long-term survival. GSTM1 was significantly downregulated in COAD versus normal tissues. Infiltration levels of B cells, CD8+ T cells, and dendritic cells were closely correlated to GSTM1 gene copy number deletion, and GSTM1 expression levels in COAD positively correlated with dendritic cell, B cell, neutrophil, and macrophage infiltration. Functional enrichment analysis indicated 36 GSTM1-related immunomodulators are involved in immune-related pathways of regulating T cell activation and lymphocytic activation. A 2-gene prognostic risk signature based on the 36 GSTM1-related immunomodulators was built using the Cox regression model, and the risk signature in combination with stage had an area under the curve (AUC) value of 0.747 by the receiver operating characteristic method. patients with higher risk scores-calculated based on 2 gene prognostic risk characteristics and further identified as an independent prognostic factor-were associated with worse survival using the Kaplan-Meier analysis. Together, the clinical nomogram and calibration curve based on GSTM1 suggested a good prediction accuracy for long-term survival probability. Our study provided evidence supporting the significant role of GSTM1 in COAD immunity and suggests GSTM1 as a potential novel target for COAD immunotherapy.