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Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer.

ABSTRACT: Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)₂D₃. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression.

SUBMITTER: Diaz Cruz MA

PROVIDER: S-EPMC8060222 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective: This study aims to explore the clinical significance of haptoglobin (HP) and protein disulfide-isomerase A3 (PDIA3) in human serum in the screening, diagnosis and staging of colorectal cancer (CRC), and to provide novel screening approaches featuring high specificity, sensitivity, and accuracy for early screening and diagnosis of clinical colorectal cancer. Methods: 88, 77, and 36 blood specimens were respectively harvested from colorectal cancer patients, colorectal polyp patients, and normal subjects (the health examination) who requested medical assistance from our hospital between Oct2019 and February 2022. The serum contents of HP and PDIA3 in each sample were determined through an enzyme linked immunosorbent assay (ELISA). This step was taken to analyze the differences among different specimen groups in terms of the serum contents of HP and PDIA3, to analyze the relationships between the expression levels of HP and PDIA3 and the pathological characteristics of colorectal cancer, and to explore the critical role of HP and PDIA3 in the screening, diagnosis, and staging of colorectal cancer. Results: Serum contents of HP and PDIA3 were higher in colorectal cancer patients, with statistical differences (p < 0.05), than those in the colonic polyp patients and healthy subjects. Receiver operating characteristic (ROC) curve demonstrated that the cut-offs of HP and PDIA3 serum contents indicating colorectal cancer were 149 ug/ml and 66 ng/ml respectively. The individually and jointly tested AUCs of HP (0.802) and PDIA3 (0.727) were higher than those of serum CEA and CA199, the sensitivity and specificity of HP were 64.8 and 91.2%, the sensitivity and specificity of PDIA3 were 65.9 and 71.7%. Moreover, the contents of HP and PDIA3 increased alongside disease progression, with differences (p < 0.05). Conclusion: Our research indicated that joint testing of HP and PDIA3 was of reference value for progressive stage and reliable biological indicators of colorectal cancer screening.

Dataset Information

Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer.

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