Lactate-dehydrogenase 5 is overexpressed in non-small cell lung cancer and correlates with the expression of the transketolase-like protein 1.
OBJECTIVE
As 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.


METHODS
Primary 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.


RESULTS
89.5% (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.


CONCLUSIONS
LDH5 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.
Kayser
Gian
G
Institute of Pathology, University Hospital Freiburg, Freiburg, Germany. gian.kayser@uniklinik-freiburg.de
Kassem
Ahmad
A
Sienel
Wulf
W
Schulte-Uentrop
Luzie
L
Mattern
Dominik
D
Aumann
Konrad
K
Stickeler
Elmar
E
Werner
Martin
M
Passlick
Bernward
B
zur Hausen
Axel
A
D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000032:analysis* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D014174:Transketolase / Q000032:analysis* / Q000378:metabolism; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C505431:TKTL1 protein, human; D014174:Transketolase; D005947:Glucose
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