title: Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer.
abstract: OBJECTIVE
  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 χ(2) 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Xu-Ren
authors.initials: XR
authors.lastname: Sun
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Guan
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Chen-Yan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Jun-Yan
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Zhang
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Hui-Jing
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Hui-Mian
authors.initials: HM
authors.lastname: Xu
authors.affiliation: Xu-Ren Sun, Yi-Ning Zhang, Ming-Jun Sun, Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
authors.forename: Ming-Jun
authors.initials: MJ
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016009:Chi-Square Distribution; D002681:China; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000032:analysis*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D030481:Pyruvate Dehydrogenase (Lipoamide)
keywords: Gastric carcinoma; Immunohistochemical analysis; Prognosis; Pyruvate dehydrogenase; Tissue microarray