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

Shimoda,Tomohiro; Wada,Ryuichi; Kure,Shoko; Ishino,Kousuke; Kudo,Mitsuhiro; Ohashi,Ryuji; Fujita,Itsuo; Uchida,Eiji; Yoshida,Hiroshi; Naito,Zenya

doi:10.3892/or.2019.6999

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

Authors:
- Tomohiro Shimoda
- Ryuichi Wada
- Shoko Kure
- Kousuke Ishino
- Mitsuhiro Kudo
- Ryuji Ohashi
- Itsuo Fujita
- Eiji Uchida
- Hiroshi Yoshida
- Zenya Naito
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Affiliations: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan, Department of Diagnostic Pathology, Nippon Medical School Musashi Kosugi Hospital, Kawasaki, Kanagawa 211‑8533, Japan, Department of Gastrointestinal and Hepato‑Biliary‑Pancreatic Surgery, Nippon Medical School, Tokyo 113-8602, Japan
Published online on: February 5, 2019 https://doi.org/10.3892/or.2019.6999
Pages: 2265-2272

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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.

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