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Overexpression of metabolic markers PKM 2 and LDH 5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer
Author(s) -
Yuan Chunping,
Li Zhongwu,
Wang Yanling,
Qi Bin,
Zhang Wei,
Ye Jinhai,
Wu Heming,
Jiang Hongbin,
Song LiangNian,
Yang Jianrong,
Cheng Jie
Publication year - 2014
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12441
Subject(s) - pkm2 , immunohistochemistry , lactate dehydrogenase , western blot , metastasis , cancer research , medicine , cancer , pathology , pyruvate kinase , biology , glycolysis , enzyme , gene , biochemistry , metabolism
Aims Pyruvate kinase M 2 ( PKM 2) and lactate dehydrogenase 5 ( LDH 5) are two metabolic and oncogenic markers of cancer. In this study, we sought to investigate their expression patterns and prognostic value in tongue squamous cell carcinoma ( TSCC ). Methods and results The expression and subcellular localization of PKM 2 and LDH 5 in TSCC cell lines were determined by W estern blot and immunofluorescence. PKM 2 and LDH 5 abundance was examined by immunohistochemistry in 63 TSCC tumour specimens; their association with multiple clinicopathological parameters and overall patient survival was assessed. The protein levels of PKM 2 and LDH 5 were both significantly higher in TSCC cells than in an immortalized oral epithelial cell line. Overexpression of PKM 2 associated significantly with cervical node metastasis ( P = 0.0373), while elevated LDH 5 levels correlated significantly with tumour size ( P = 0.0094), pathological grade ( P = 0.0052), cervical node metastasis ( P = 0.0023) and clinical stage ( P = 0.0024). Patients with tumours showing an increase in either PKM 2 or LDH 5 expression displayed significantly reduced overall survival, while patients with tumours overexpressing both proteins showed the worst prognosis with lowest overall survival. Furthermore, PKM 2 and LDH 5 were identified as independent prognostic predictors for overall patient survival in TSCC . Conclusion Our data indicate that overexpression of PKM 2 and LDH 5 associates with key clinicopathological features and unfavourable prognosis in TSCC .