Expression of protein disulfide isomerase�A3 and its clinicopathological association in gastric cancer

Abstract

Protein disulfide isomerase A3 (PDIA3) is a chaperone protein that supports the folding and processing of synthesized proteins. Its expression is associated with the prognosis of laryngeal cancer, hepatocellular carcinoma, diffuse glioma and uterine cervical cancer. In the present study, the expression levels of PDIA3 and its clinicopathological association were examined in 52 cases of gastric cancer (GC). The expression of PDIA3 was examined by immunohistochemistry and scored using a semi-quantitative method. According to the score, GC samples were classified into PDIA3-High and PDIA3-Low GC. PDIA3-High GC samples were predominantly of the intestinal type. Multivariate survival analysis indicated that PDIA3 expression and cancer stage were independent factors. The overall survival of PDIA3-High GC cases was significantly favorable compared with that of PDIA3-Low GC cases, and this was more evident in cases at an advanced stage. In GC cell cultures, the PDIA3 and major histocompatibility complex (MHC) class I proteins were expressed in three out of the four assessed cell lines according to western blot analysis. Notably, the expression of MHC class I was increased by the stimulation of interferon γ. Co-immunoprecipitation assays suggested the formation of a PDIA3 and MHC class I complex. The findings suggested that PDIA3 may be involved in the immune response of carcinoma cells. The improved prognosis in PDIA3-High GC may be accounted for, in part, by sufficient antigen processing and expression of MHC class I, which can be mediated by PDIA3. It was suggested that PDIA3 serves an important role in the pathobiology of GC, and that PDIA3 is a useful marker for the prediction of prognosis.

A Novel Three-Gene Model Predicts Prognosis and Therapeutic Sensitivity in Esophageal Squamous Cell Carcinoma

“…PDIA3 expression level is correlated with the clinical outcome of patients with ovarian carcinoma who receive chemoradiotherapy, and the sensitivity to paclitaxel can be enhanced by PDIA3 silencing [47, 48]. In ESCC, we found that PDIA3 decreased gradually with the progress of stage and related to favorable prognosis, which was in accord with the findings in gastric cancer [49], but contrary to those in hepatocellular carcinoma [50]. The favorable prognostic value of PDIA3 in ESCC implies that ESCC patients with high expression of PDIA3 may be more sensitive to chemotherapy such as paclitaxel, but further studies are warranted.…”

Insights into the role of ERp57 in cancer

“…However, ERp57 exerts the opposite effect on gastric cancer progression; its expression is significantly decreased in gastric cancer and metastases, and low levels of ERp57 are correlated with an increased depth of tumor invasion and advanced disease stage [37]. The results of retrospective analysis have shown that high expression indicates favorable overall survival in gastric cancer patients [38]. ERp57 is also related to gastric cancer treatment.…”

Inhibitor for protein disulfide‑isomerase family A member 3 enhances the antiproliferative effect of inhibitor for mechanistic target of rapamycin in liver cancer: An in vitro study on combination treatment with everolimus and 16F16

“…Liver cancer with high PDIA3 expression follows an unfavorable course and is characterized by high proliferation activity and a low frequency of cell death. The expression of PDIA3 and its association with prognosis has been reported for other carcinomas (21,22,(38)(39)(40)(41). Furthermore, knock-down of PDIA3 may enhance the effect of radiation therapy in laryngeal cancer (38) and breast cancer (42).…”