title: Clinicopathological significance and prognostic value of lactate dehydrogenase A expression in gastric cancer patients.
abstract: BACKGROUND
  LDH-A, the enzyme responsible for transforming pyruvate into lactate, has been demonstrated to be up-regulated in many types of cancer and to give rise to more aggressive behavior by regulating proliferation and anti-apoptosis. However, its expression in gastric cancer (GC) has not been characterized thoroughly. The purpose of this study was to clarify the expression and potential impact of LDH-A in GC.
  
  
  METHODS
  We examined LDH-A expression by immunohistochemistry on GC tissue microarray (TMA) and using Western blot on fresh GC tissues and cell lines. Prognostic value and correlation with other clinicopathologic factors were evaluated. We transfected siRNA into GC cells against LDH-A. LDH-A was analyzed by Western blotting and real-time RT-PCR. Cell growth was evaluated in vitro and in vivo. Lactate and ATP production by cells were determined.
  
  
  RESULTS
  There was significantly higher LDH-A expression in carcinoma than in non-neoplastic mucosa (NNM). There was a positive correlation of LDH-A expression with age, histological type and Lymph node metastases. Survival analysis demonstrated that high expression of LDH-A in GC was associated with lower overall survival (OS). When stratified by Lauren grade and histological classification, significance appeared in diffuse type and undifferentiated type GC. In multivariate analysis, the LDH-A expression in GC was an independent prognostic risk factor for OS (hazard ratio = 1.829, 95%CI 1.375-2.433,P<0.0001). Specific siRNA against LDH-A in GC cell line retarded cell growth both in vitro and in mouse models. LDH-A knockdown also reduced lactate and ATP production in GC cells.
  
  
  CONCLUSIONS
  Our study indicated the oncogenic role of LDH-A in GC. LDH-A expression is an independent prognostic risk factor in GC patients and up-regulated expression of LDH-A could be predictive of poor outcomes in diffuse type and undifferentiated type GC. Our results suggested that LDH-A might be a potential therapeutic target in gastric cancer.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Xuren
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology and Metabolism, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Huimian
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China; Department of Gastrointestinal Endoscopy, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Sun
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D007773:Lactates / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D007527:Isoenzymes; D007773:Lactates; D034741:RNA, Small Interfering; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5