title: High lactate dehydrogenase 5 expression correlates with high tumoral and stromal vascular endothelial growth factor expression in gastric cancer.
abstract: BACKGROUND
  Lactate dehydrogenase 5 (LDH5) is a major lactate dehydrogenase isoenzyme catalyzing the transformation of pyruvate to lactate to provide anaerobic energy. Vascular endothelial growth factor (VEGF) is expressed in both tumor and stromal cells in gastric cancer. Our aim was to study the prognostic effect of LDH5, and tumoral and stromal expression of the angiogenic factor VEGF in gastric cancer, and the intercorrelation of tissue expression of both factors.
  
  
  METHODS
  Tissue microarray analysis of 382 consecutive gastric cancer resection specimens was used for immunohistochemistry of LDH5 and VEGF, and expression of LDH5, tumoral VEGF, and stromal VEGF was categorized into low and high groups.
  
  
  RESULTS
  High expression was observed for LDH5 in 57.9% (219/378), tumoral VEGF in 35.7% (136/381), and stromal VEGF in 58.5% (223/381) of the specimens. Regarding high expression of LDH5 and VEGF, significant associations with intestinal type, advanced gastric cancer, lymph node metastasis, higher TNM stage, and upper-third location were noted. Positive intercorrelations occurred among the expression of LDH5 and VEGF. Results of survival analyses revealed a significant association of high expression of LDH5 and VEGF with lower survival (overall and disease-free survival). Five-year survival rates were significantly lower in tumors with high LDH5 and tumoral VEGF expression in diffuse- or mixed-type cancers and high expression of stromal VEGF in intestinal-type cancer.
  
  
  CONCLUSIONS
  The results of our study showed that high LDH5 and VEGF expression in both tumor and stroma was a prognostic factor for patients with gastric cancers, especially diffuse- or mixed-type cancers. Therefore, LDH5 expression may play a role in the regulation of tumoral and stromal VEGF expression in gastric cancer. Our results suggest the potential use of LDH5 expression as a biomarker for response to VEGF-targeted therapy.
authors.affiliation: Department of Pathology, Chung Ang University, Seoul, Republic of Korea.
authors.forename: Hee Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Hee Eun
authors.initials: HE
authors.lastname: Lee
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000096:biosynthesis*; D000080864:Lactate Dehydrogenase 5; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5