Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis.
BACKGROUND
Lactate-dehydrogenase-5 (LDH-5) is an important isoenzyme converting pyruvate to lactate under hypoxic conditions and might play an important role in the development and progression of malignancies. However, the role of LDH-5 in gastric cancer is still unclear. In this study, we investigated the clinical significance of LDH-5 expression in gastric carcinoma.


METHODS
LDH-5 expression in 152 patients with different grade and stage gastric carcinoma was analyzed by immunohistochemistry. In addition, hypoxia-inducible factor 1alpha (HIF-1alpha) as a marker of tumor hypoxia, as well as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) as angiogenesis parameters were also assessed in this study. Correlations between the expression of investigated proteins and various clinicopathological factors including survival were determined.


RESULTS
There were 94 cases (61.8%) showing high LDH-5 expression, and 95 patients (62.5%) had high HIF-1alpha expression. Positive correlation was found between LDH-5 expression and HIF-1alpha, VEGF, and COX-2. The overexpression of LDH-5 was more prevalent in advanced tumors having positive vessel invasion. Patients with overexpression of LDH-5 showed far lower disease-free (63.5% vs 82.7%) and overall (56.3% vs 78.4%) survival rates compared with patients with low LDH-5 expression. HIF-1alpha expression was shown to have no significance on survival. In multivariate analysis, high LDH-5 expression kept its independence as a negative prognostic indicator.


CONCLUSIONS
The results of the current study show that LDH-5 expression may be a useful prognostic factor for patients with gastric carcinoma.
Surgical Oncology Department, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. kolev.srg2@tmd.ac.jp
Yanislav
Y
Kolev
Hiroyuki
H
Uetake
Yoko
Y
Takagi
Kenichi
K
Sugihara
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000080864:Lactate Dehydrogenase 5; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics*; D015996:Survival Rate; D015854:Up-Regulation
D043925:Angiogenesis Inducing Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5