Protein disulfide isomerase A3 as novel biomarker for endometrial cancer

OBJECTIVE: This study aims to investigate the potential of PDIA3 as a novel prognostic biomarker and therapeutic target for Endometrial Cancer (EC) with the ultimate goal of improving survival rates in EC patients. METHODS: This study employed a combination of public database analysis and clinical tissue sample assays. The analysis included comparing the gene expression of PDIA3 between EC and adjacent paracancerous tissues, investigating this expression status using qPCR and immunohistochemistry (IHC) assays, studying the correlation of expression with different parameters using Chi-square test, Cox Regression, and log-rank test, as well as exploring the PDIA3-related immune infiltration and metabolic pathway using TIMER and GSEA. RESULTS: The analysis of public datasets revealed that PDIA3 mRNA and protein expression was significantly higher in EC tissues compared to adjacent tissues (P = 4.1e-03, P = 1.95e-14, and P = 1.6e-27, respectively). The qPCR analysis supported this finding (P = 0.029). IHC analysis revealed a significant increase in PDIA3 expression in endometrial cancer (EC) tissues compared to adjacent normal tissues (P = 0.01). Furthermore, PDIA3 expression showed significant correlations with cancer stage and tumor grade. Multivariate Cox regression analysis suggested that the PDIA3 gene holds promise as a prognostic factor for EC patients (HR = 0.47, 95% CI [0.27, 0.82], P = 0.008). The results from TIMER demonstrated a positive correlation between PDIA3 and tumor-infiltrating CD8 T cells and macrophages, and a negative correlation with tumor-infiltrating CD4 T cells. Additionally, the GSEA results indicated that PDIA3 overexpression was associated with various metabolic processes in EC patients. CONCLUSION: PDIA3 has been validated as a potential biomarker for EC, and its expression is further associated with pathological staging and prognosis.