Identification of a novel Protein Disulfide-isomerase A3 (PDIA3) transcript variant as a potential biomarker associated with late stage prostate cancer

Abstract

Background Prostate cancer (PC) is a heterogeneous and unpredictable disease and becomes untreatable when the tumor progress to castrate-resistant (CR) or androgen independent (AI). A major clinical challenge in prostate cancer is the lack of diagnostic and prognostic tests that distinguish between benign and aggressive tumors. Isoforms of gene transcripts are emerging as suitable candidates to represent disease progression. Vitamin D receptor (VDR and PDIA3) transcript isoforms could be the target candidates of study since they have been related with anti-tumoral effects and carcinogenesis in several cancer types. Methods The current study investigates the role of vitamin D receptor transcript isoforms in prostate cancer progression by using Next Generation Sequencing (NGS), Droplet Digital PCR (ddPCR) and several functional prediction tools. Results The NGS analysis revealed a novel PDIA3 transcript isoform (PDIA3N) that is higher expressed than the PDIA3 isoform that codifies for the receptor protein, in prostate cells. The expression of PDIA3N was validated by droplet digital PCR (ddPCR) absolute quantification, which confirmed the findings from the NGS analyses. The PDIA3N isoform was present in higher levels than PDIA3, in the metastatic androgen dependent LNCaP cells. Furthermore, analysis of the novel PDIA3 isoform sequence indicate that the variations present in its sequence are altering the original protein function and structure as well as the predicted subcellular localization of the protein. Conclusions We conclude that, PDIA3N due to the high expression in LNCaP cells and its abnormality in predicted structure, localization and function, is a potential biomarker for prostate cancer disease that needs to be further investigated in prostate cancer samples.