Expression characteristics analysis, establishment of prognostic model and screening of key regulators based on selenium protein-related genes in rectal adenocarcinoma.

BACKGROUND: Selenium is an essential trace element in the human body and plays a significant role in multiple cancers. This study aims to comprehensively explore the expression characteristics and prognostic value of selenium-related genes in rectal adenocarcinoma (READ), and investigate the biological effects of selenium supplement on READ cells. METHODS: The differentially expressed genes (DEGs) between control samples and READ samples were analyzed based on TCGA-READ cohort. The MSigDB database was used to obtain the selenium-related gene sets. A comprehensive method integrating 10 different machine learning algorithms and 101 combinations was used to construct a prognostic risk model. GSE87211 and GSE133057 datasets were used as validation sets to evaluate the diagnostic and predictive capabilities of the prognostic risk model. Additionally, the biological effects of Na2SeO3 on the viability, apoptosis and oxidative stress indicators of READ cell were also analyzed. RESULTS: 19 selenium-related genes in READ were identified, which were involved in biological processes such as cell proliferation, macrophage chemotaxis, and oxidative stress response, as well as pathways such as glutathione metabolism, selenium metabolism, and oxidative stress response. 4 core genes (FOS, PTGS1, SELENOP, and XDH) were screened out, and a prognostic risk model was constructed. The risk score had good predictive value for READ patients, and the patients with high risk scores had shorter overall survival time. The risk score was related to the infiltration levels of most immune cells. The patients with low risk scores were more sensitive to drugs such as BAY.61.3606, BMS.754807, and Embelin. Na2SeO3 treatment inhibited the viability of READ cells, promoted apoptosis and G2/M phase arrest. Na2SeO3 treatment increased xanthine oxidase activity and glutathione levels, and decreased reactive oxygen species and malonaldehyde levels. CONCLUSION: The dysregulation of selenium-related genes may be associated with the progression of READ, and they are helpful for READ patients stratification. Selenium supplementation may exert anti-tumor effects by regulating oxidative stress and cell cycle. Selenium-related proteins are potential biomarkers and candidate targets for READ.