Glutathione peroxidase 2: A key factor in the development of microsatellite instability in colon cancer

Abstract

Background: Much research has focused on detecting microsatellite instability (MSI), which is frequently employed in the diagnosis and treatment of patients with colon cancer. However, the causes and progression of MSI in colon cancer have not yet been thoroughly elucidated. In this study, we screened and validated the genes associated with MSI in colorectal adenocarcinoma (COAD) using bioinformatics analysis.

Methods: MSI-related genes of COAD were obtained from the Gene Expression Omnibus dataset, Search Tool for the Retrieval of Interaction Gene/Proteins, Gene Set Enrichment Analysis, and Human Protein Atlas. The function, prognostic value, and immune connection of MSI-related genes in COAD were examined using Cytoscape 3.9.1, the Human Gene Database, and the Tumor IMmune Estimation Resource. Key genes were verified using The Cancer Genome Atlas database and immunohistochemistry of clinical tumor samples.

Results: We identified 59 MSI-related genes in patients with colon cancer. The protein interaction network of these genes was developed, and numerous functional modules associated with MSI were discovered. Pathways related to MSI were identified using KEGG enrichment analysis, and these included chemokine signaling, thyroid hormone synthesis, cytokine receptor interaction, estrogen signaling, and Wnt signaling pathways. Further analyses were used to identify the MSI-related gene, glutathione peroxidase 2 (GPX2), which was closely related to the occurrence of COAD and tumor immunity.

Conclusions: In COAD, GPX2 may be crucial for the establishment of MSI and tumor immunity, and its deficiency may result in MSI and immune cell infiltration in colon cancer.

Keywords: Colon cancer; Glutathione peroxidase 2; Microsatellite instability; Prognostic.