Abstract:
Protein disulfide isomerase A3 (PDIA3) is a kind of thiol oxidoreductase
with a wide range of functions, and its expression is elevated in a variety of tumors, which is closely related to the invasion and metastasis of tumor cells, and has a significant impact on the immunogenicity of tumor cells.This study aims to analyze the differential expression of PDIA3 in cervical cancer, lung adenocarcinoma and pan-cancer, evaluate its clinical prognostic significance and possible mechanism of action in different cancers, and explore its ability to regulate tumor immunity as a biomarker. This study was performed by downloading multi-level data containing 33 cancers from The Cancer Genome Atlas (TCGA), UCSC Xena, Cancer Cell Lineage Encyclopedia (CCLE), Genotype Tissue Expression (GTEx), and GDC. R software was used to conduct log2 standardization on gene expression data. The Wilcoxon rank sum test was used to compare the differential expression of PDIA3 gene between cancer and adjacent tissue samples in different tumors. The survival prognosis was analyzed by Kaplan-Meier method, log-rank test and Cox proportional risk regression model. Correlation analysis between the two variables was performed using Spearman's test or Pearson's test. At the same time, 111 cases of cervical cancer tissue and 24 cases of paracancerous tissue samples containing clinical characteristics were collected for immunohistochemical test verification. Bioinformatics methods were applied to analyze the differential expression levels of PDIA3 in pan-cancer and its clinical prognostic significance. Based on the pan-cancer study, the differential expression profile, survival prognostic value and clinical significance of PDIA3 in cervical cancer and lung adenocarcinoma were further explored. The analysis results showed that: (1) PDIA3 was highly expressed in 19 types of cancers, but down-regulated only in THCA. The expression level of PDIA3 in THYM has the strongest correlation with TMB and MSI. The methylation level of PDIA3 promoter region was closely related to patient outcome in eight tumors. (2) The expression of PDIA3 in cervical cancer is higher than that in normal tissues, which was significantly increased with
the progression of tumor stage; The high expression of PDIA3 gene is associated with poor prognosis in patients with cervical cancer.The genes positively correlated with PDIA3 expression included HSPA5, PPIB, and HSP90B1, which were mainly enriched in biological processes such as endoplasmic reticulum protein folding, endoplasmic reticulum stress response. (3) PDIA3 expression was higher in lung adenocarcinoma tissues than in normal tissues, and PDIA3 showed moderate staining in normal lung tissues and strong staining in tumor tissues.High expression of PDIA3 gene is associated with poor prognosis of LUAD.In TIMER, after adjustment for tumor purity, PDIA3 expression levels were significantly correlated with 21 of the 33 immune cell markers in LUAD and significantly positively correlated with immune checkpoint expression. This study suggests that PDIA3 plays an important role in the occurrence and development of KIRP, KICH, and CESC and in the immunotherapeutic response of THYM, READ, and LGG. PDIA3 may affect lung adenocarcinoma development by regulating tumor infiltrating cells in TME, and PDIA3 can be used as a prognostic biomarker for these tumors.
Audience Take Away Notes:
- Existing studies have shown that PDIA3 is closely related to the occurrence and development of a variety of diseases. Detection or intervention of PDIA3 expression levels in relevant sites may become a new target for early diagnosis and treatment of diseases
- At present, the understanding of PDIA3 is not completely clear, and further research is needed. For example, in-depth exploration of the biological function of PDIA3 can promote the understanding of the mechanism of related diseases, and studying the changes of PDIA3 in various related diseases will help to have a more comprehensive understanding of PDIA3
- PDIA3 is a reactive change in the development of the disease, or the leading cause of the development of the disease is still worthy of in-depth exploration, at the same time, gene intervention will become the main means to deepen the study of the therapeutic effect of PDIA3
