Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma

Abstract

The prognosis of hepatocellular carcinoma (HCC) is unfavorable following complete tumor resection. The aim of the present study was to identify a molecule able to predict HCC prognosis through comprehensive protein profiling and to elucidate its clinicopathological significance. Comprehensive protein profiling of HCC was performed by liquid chromatography-tandem mass spectrometry. Through the bioinformatic analysis of proteins expressed differentially in HCC and non-HCC tissues, protein disulfide-isomerase A3 (PDIA3) was identified as a candidate for the prediction of prognosis. PDIA3 expression was subsequently examined in 86 cases of HCC by immunostaining and associations between PDIA3 expression levels and clinicopathological characteristics were evaluated. The Ki-67 index and apoptotic cell death of carcinoma cells were examined by immunostaining and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay in 24 cases. The results demonstrated that PDIA3 was expressed in all 86 HCC cases; 56 HCC cases (65%) exhibited high expression of PDIA3 and 30 (35%) exhibited low expression. The disease-free and overall survival times of HCC patients with high PDIA3 expression were significantly shorter than in HCC patients with low expression. Furthermore, increased expression of PDIA3 was associated with an elevated Ki-67 index, indicating increased cancer cell proliferation and a reduction in apoptotic cell death. Taken together, these results suggest that PDIA3 expression is associated with tumor proliferation and decreased apoptosis in HCC, and that increased expression of PDIA3 predicts poor prognosis. PDIA3 may therefore be a key molecule in the development of novel targeting therapies for patients with HCC.

Shotgun label‐free proteomic analysis for identification of proteins in HaCaT human skin keratinocytes regulated by the administration of collagen from soft‐shelled turtle

“…In this study, we used a gel‐free LC–MS‐based proteomics approach to examine the functional effects of collagen from soft‐shelled turtle on human skin. Although spectral counting may not accurately reflect the quantity information, it is useful and has been used in many studies, including those searching for novel diagnostic biomarkers . We were able to successfully identify several proteins whose expression levels were changed >2‐fold in HaCaT cells by the administration of collagen using a semiquantitative method based on spectral counting.…”

“…Although spectral counting may not accurately reflect the quantity information, 36 it is useful and has been used in many studies, including those searching for novel diagnostic biomarkers. [37][38][39][40][41][42] We were able to successfully identify several proteins whose expression levels were changed >2-fold in HaCaT cells by the administration of collagen using a semiquantitative method based on spectral counting. To examine the role of these identified proteins, we performed GO analysis.…”

Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

“…A high frequency of PDIA3-STAT3 complex formation is a marker of poor prognosis and increases resistance to radiotherapy in laryngeal cancer through modulation of STAT3 activity (19). We have previously reported that the PDIA3 expression levels in HCC tissues are higher than those in adjacent non-cancerous tissues, and that they are associated with overall survival time (20). However, the biological role of PDIA3 in HCC remains unclear.…”

Oxidatively Modified Protein‐Disulfide Isomerase–Associated 3 Promotes Dyskerin Pseudouridine Synthase 1–Mediated Malignancy and Survival of Hepatocellular Carcinoma Cells

“…Reports have shown that PDIA3 levels were high in the sera of patients with HCC as well as in HCC tissues compared to those in healthy liver or nontumors. (27,28) Interestingly, we found that PDIA3 is also oxidatively modified in HCC cells under high ROS levels, resulting in its redistribution and changes in its function. Among the oxidative modifications of PDIA3, we found that modification of M338 is important for changes in PDIA3 functions.…”