Glutathione Peroxidase 3 (GPX3) Expression Predicts the Prognosis of Numerous Malignant Tumors: A Pan-Cancer Analysis

Abstract Background: Malignant tumor is a general term for uncontrollable growth of cells. Several studies have investigated that role of GPX3 in tumors. However, no pan-cancer analysis has be conducted to assess the diagnostic and prognostic potential of GPX3. Methods: GPX3 mRNA and protein expression profile was analyzed in the TCGA+GTEx database and CPTAC database. Kaplan-Meier survival curves and forest plots were constructed to help evaluate the impact of GPX3 on the survival and prognosis of cancer patients. Gene mutations of GPX3 were analyzed based on TMB/MSI. The correlation between GPX3 and tumor immune infiltration was assessed using TIMER2. Enrichment analysis was performed to determine tumor-related signaling pathways associated with GPX3. A prediction model for STAD was established. Results: GPX3 was downregulated in most malignant tumors, and was significantly associated with the survival and prognosis of malignant tumors, such as STAD, PAAD, COAD, etc. Moreover, GPX3 expression was positively correlated and negatively with MSI in 13 and 20 categories of tumor respectively after GPX3 expression was positively correlated and negatively with TMB in 9 and 24 tumors separately (P<0.05). A positive correlation was found between GPX3 and the infiltration level of major immune cells and Cancer-associated fibroblasts (P<0.05). The effects of GPX3 were mediated by the AMPK signaling pathway, fructose and mannose metabolism. Conclusions: This is a novel pan-cancer analysis on the relationship between GPX3 and human tumors. Findings of this research will deepen our understanding on the role of GPX3 in the development, regulation and prognosis of malignant tumors.