title: 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.
authors.affiliation: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan; Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takata
authors.affiliation: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Faculty of Pharmacy, Kinki University, Osaka 577-8502, Japan.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan; Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ueda
authors.affiliation: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Ishino
authors.affiliation: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Peng
authors.affiliation: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Wada
authors.affiliation: Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Taniai
authors.affiliation: Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Gastrointestinal Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Uchida
authors.affiliation: Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Zenya
authors.initials: Z
authors.lastname: Naito
keywords: apoptosis; hepatocellular carcinoma; prognosis; proliferation; protein disulfide-isomerase A3