%0 Journal Article
%T Lactate Dehydrogenase 5 Expression in Non-Hodgkin Lymphoma Is Associated with the Induced Hypoxia Regulated Protein and Poor Prognosis
%A Renquan Lu
%A Minglei Jiang
%A Zhujun Chen
%A Xiaofeng Xu
%A Hongfeng Hu
%A Xinmin Zhao
%A Xiang Gao
%A Lin Guo
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0074853
%X Lactate dehydrogenase 5 (LDH-5) is one of the major isoenzymes catalyzing the biochemical process of pyruvate to lactate. The purpose of this study was to investigate the expression of serum LDH-5 and test whether this enzyme is regulated by tumor hypoxia and represents a prognostic marker in patients with Non-Hodgkin¡¯s lymphoma (NHL). In this study, LDH-5 levels were detected using agarose gel electrophoresis in NHL patients (n = 266) and non-NHL controls including benign lymphadenectasis (n = 30) and healthy cohorts (n = 233). We also explored the expression of LDH-5 and hypoxia-inducible factor (HIF) 1¦Á in NHL and benign controls by immunohistochemistry and immunofluorescence staining, respectively. Moreover, the role of LDH-5 in the progression of NHL was assessed by multivariate Cox analyses and Kaplan-Meier survival estimates. Serum concentrations of LDH-5 were significantly higher in NHL patients (9.3%) than in benign patients and healthy controls (7.5% and 7.2%, respectively, P<0.01). Application of LDH-5 detection increased the sensitivity of NHL detection, identifying 53.4% of NHL patients as positive, compared with the measurement of total LDH levels (36.5% sensitivity). LDH-5 concentrations increased with clinical stage, extra-nodal site involvement, and WHO performance status of patients with NHL. Exposure to a hypoxic environment induced the expression of LDH-5 and its overexpression correlated with HIF1¦Á cytoplasmic accumulation in NHL cells. In multivariate analyses, LDH-5 was an independent marker for progression-free survival in patients with NHL (P<0.001). Overall, the expression of LDH-5 was elevated in NHL, showing an association with tumor hypoxia and unfavorable prognosis. Thus, LDH-5 emerges as a promising prognostic predictor for NHL patients.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0074853