High expression of PDIA4 promotes malignant cell behavior and predicts reduced survival in cervical cancer

Abstract

The protein disulfide isomerase (PDI) gene family plays important roles in the maintenance of several cellular functions. Previous studies have showed that protein disulfide isomerase family A member 4 (PDIA4) is aberrantly expressed in several types of cancer, and correlates with prognosis of patients. However, the role of PDIA4 in cervical cancer remains unclear. In the present study, the expression pattern of PDIA4 from both public database and immunohistochemical analysis in cervical samples was analyzed. Cell Counting Kit‑8 and Transwell assays were performed to determine the effect of PDIA4 on cervical cancer cell proliferation and migration. Gene set enrichment analysis (GSEA) was used to provide the associated enriched pathways of PDIA4 in regulating cervical tumorigenesis. It was observed that mRNA expression and protein level of PDIA4 were upregulated in cervical cancer tissues. High expression of PDIA4 was significantly associ‑ ated with poor overall survival (P=0.0095) and relapse‑free survival (P=0.0019) in The Cancer Genome Atlas cohort. Knockdown of PDIA4 inhibited cervical cancer cell prolifera‑ tion and migration. Moreover, PDIA4 affected the expression of proliferation‑related molecules (cyclin D1 and PCNA) and migration‑related molecules (E‑cadherin and Vimentin). Additionally, GSEA revealed that PDIA4 was significantly associated with gene signatures involving glycan biosyn‑ thesis, glycosaminoglycan degradation and protein export. In conclusion, the present findings highlighted the importance of PDIA4 in cervical oncogenesis, and suggested that targeting PDIA4 may be a potential therapeutic application for cervical cancer.