Abstract
AimsAs one of the five Lactate dehydrogenase (LDH) isoenzymes, LDH5 has the highest efficiency to catalyze pyruvate transformation to lactate. LDH5 overexpression in cancer cells induces an upregulated glycolytic metabolism and reduced dependence on the presence of oxygen. Here we analyzed LDH5 protein expression in a well characterized large cohort of primary lung cancers in correlation to clinico-pathological data and its possible impact on patient survival.MethodsPrimary lung cancers (n = 269) and non neoplastic lung tissue (n = 35) were tested for LDH5 expression by immunohistochemistry using a polyclonal LDH5 antibody (ab53010). The results of LDH5 expression were correlated to clinico-pathological data as well as to patient's survival. In addition, the results of the previously tested Transketolase like 1 protein (TKTL1) expression were correlated to LDH5 expression.Results89.5% (n = 238) of NSCLC revealed LDH5 expression whereas LDH5 expression was not detected in non neoplastic lung tissues (n = 34) (p < 0.0001). LDH5 overexpression was associated with histological type (adenocarcinoma = 57%, squamous cell carcinoma = 45%, large cell carcinoma = 46%, p = 0.006). No significant correlation could be detected with regard to TNM-stage, grading or survival. A two sided correlation between the expression of TKTL1 and LDH5 could be shown (p = 0.002) within the overall cohort as well as for each grading and pN group. A significant correlation between LDH5 and TKTL1 within each histologic tumortype could not be revealed.ConclusionsLDH5 is overexpressed in NSCLC and could hence serve as an additional marker for malignancy. Furthermore, LDH5 correlates positively with the prognostic marker TKTL1. Our results confirm a close link between the two metabolic enzymes and indicate an alteration in the glucose metabolism in the process of malignant transformation.
Highlights
As one of the five lactate dehydrogenase (LDH) isoenzymes, LDH5 has the highest efficiency to catalyze pyruvate transformation to lactate
LDH5 is overexpressed in malignant neoplastic lung tissue In none of the 34 non-neoplastic lung tissue samples LDH5 expression could be detected by immunohistochemistry
Only 28 cases (10.53%) of all the non small cell lung cancer (NSCLC) samples were negative for LDH5 expression
Summary
As one of the five lactate dehydrogenase (LDH) isoenzymes, LDH5 has the highest efficiency to catalyze pyruvate transformation to lactate. According to Warburg, malignant tumors generate lactate even in the presence of sufficient oxygen supply (Warburg effect) [1]. Upon this Thompson postulated a shift from oxidative phosphorylation to anaerobic glycol-. Recent studies on glucose degradation pathways of malignant tumors postulate a shunt between the PPP and the aerobic glycolysis (Embden-Meyerhof-pathway; EMP) with Glycerinaldehyde-3-phosphate (G3P) possibly representing the linking molecule between the two. According to these results G3P is generated from xylose5-phosphate (X5P), one endproduct of the PPP by transketolase like protein 1 (TKTL1). In a recent study we were able to demonstrate that overexpression of TKTL1 is associated with a poor outcome in patients with non small cell lung cancer (NSCLC)
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