Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2015; 21(17): 5336-5344
Published online May 7, 2015. doi: 10.3748/wjg.v21.i17.5336
Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer
Xu-Ren Sun, Zhe Sun, Zhi Zhu, Hai-Xia Guan, Chen-Yan Li, Jun-Yan Zhang, Yi-Ning Zhang, Huan Zhou, Hui-Jing Zhang, Hui-Mian Xu, Ming-Jun Sun
Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Zhe Sun, Zhi Zhu, Jun-Yan Zhang, Hui-Mian Xu, Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Hai-Xia Guan, Chen-Yan Li, Department of Endocrinology and Metabolism, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Huan Zhou, Hui-Jing Zhang, Ming-Jun Sun, Department of Gastrointestinal Endoscopy, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: Sun MJ, Xu HM designed the research; Sun XR, Sun Z, Zhu Z, Zhang YN performed the research; Guan HX, Li CY contributed new reagents and analytic tools; Sun XR, Zhang HJ, Zhou H and Zhu Z analyzed the data; Sun XR, Zhang JY, Sun Z and Zhu Z wrote the paper.
Supported by Grants from the research projects in Liaoning Province Science and Technology Department, No. 2007225017, No. 2009225011-2 and No. 2011415052; Science and Technology projects in Shenyang City, No. F11-264-1-19.
Ethics approval: The study was reviewed and approved by the Research Ethics Committee of China Medical University.
Informed consent: All study participants or their legal guardians provided informed written consent prior to study enrollment.
Conflict-of-interest: All of the authors have no conflicts of interest.
Data sharing: No additional data are available
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ming-Jun Sun, MD, Department of Gastroenterology, First Affiliated Hospital of China Medical University, No. 155 North Nanjing Street, Shenyang 110001, Liaoning Province, China. smjmw@sina.com
Telephone: +86-24-83282175 Fax: +86-24-83282175
Received: October 14, 2014
Peer-review started: October 15, 2014
First decision: December 11, 2014
Revised: December 30, 2014
Accepted: February 12, 2015
Article in press: February 13, 2015
Published online: May 7, 2015
Abstract

AIM: To investigate the expression and prognostic role of pyruvate dehydrogenase (PDH) in gastric cancer (GC).

METHODS: This study included 265 patients (194 male, 71 female, mean age 59 years (range, 29-81 years) with GC who underwent curative surgery at the First Affiliated Hospital of China Medical University from January 2006 to May 2007. All patients were followed up for more than 5 years. Patient-derived paraffin embedded GC specimens were collected for tissue microarrays (TMAs). We examined PDH expression by immunohistochemistry in TMAs containing tumor tissue and matched non-neoplastic mucosa. Immunoreactivity was evaluated independently by two researchers. Overall survival (OS) rates were determined using the Kaplan-Meier estimator. Correlations with other clinicopathologic factors were evaluated by two-tailed χ2 tests or a two-tailed t-test. The Cox proportional-hazard model was used in univariate analysis and multivariate analysis to identify factors significantly correlated with prognosis.

RESULTS: Immunohistochemistry showed that 35.47% of total cancer tissue specimens had cytoplasmic PDH staining. PDH expression was much higher in normal mucosa specimens (75.09%; P = 0.001). PDH expression was correlated with Lauren grade (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001), lymph node metastasis (65.43% with no metastasis vs 51.09% with metastasis; P = 0.033), lymphatic invasion (61.62% with no invasion vs 38.81% with invasion; P = 0.002), histologic subtypes (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001) and tumor-node-metastasis (TNM) stage (39% in poorly differentiated vs 65.91% in well differentiated and 67.11% in moderately differentiated; P = 0.001) in GC. PDH expression in cancer tissue was significantly associated with higher OS (P < 0.001). The multivariate analysis adjusted for age, Lauren classification, TNM stage, lymph node metastasis, histological type, tumor size, depth of invasion and lymphatic invasion showed that the PDH expression in GC was an independent prognostic factor for higher OS (HR = 0.608, 95%CI: 0.504-0.734, P < 0.001).

CONCLUSION: Our study indicated that PDH expression is an independent prognostic factor in GC patients and that positive expression of PDH may be predictive of favorable outcomes.

Keywords: Pyruvate dehydrogenase, Gastric carcinoma, Tissue microarray, Prognosis, Immunohistochemical analysis

Core tip: This is the first reported study to evaluate the prognostic role of pyruvate dehydrogenase (PDH) expression in gastric cancer (GC). This study showed that reduced PDH expression was correlated with Lauren grade, lymph node metastasis, lymphatic invasion, histologic subtype and TNM stage in GC. We propose that increased PDH expression may contribute to a decrease in the proliferation and development of GC. In particular, PDH protein expression was found to positively correlate with survival in GC patients, and a high level of PDH expression was found to be associated with better overall survival in patients with resected GC. In conclusion, this study showed that PDH expression is an independent prognostic factor in gastric carcinomas.