Overexpression of metabolic markers PKM2 and LDH5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer

• Published in: Histopathology 2014-11, Vol.65 (5), p.595-605
• Main Authors: Yuan, Chunping, Li, Zhongwu, Wang, Yanling, Qi, Bin, Zhang, Wei, Ye, Jinhai, Wu, Heming, Jiang, Hongbin, Song, Liang-Nian, Yang, Jianrong, Cheng, Jie
• Format: Article
• Language: English
• Subjects: Adult; aerobic glycolysis; Aged; Biomarkers, Tumor - metabolism; Carrier Proteins - metabolism; Female; Humans; Immunohistochemistry; Isoenzymes - metabolism; L-Lactate Dehydrogenase - metabolism; Lactate Dehydrogenase 5; LDH5; Male; Membrane Proteins - metabolism; Middle Aged; PKM2; Prognosis; Thyroid Hormone-Binding Proteins; Thyroid Hormones - metabolism; Tongue Neoplasms - metabolism; Tongue Neoplasms - pathology; tongue squamous cell carcinoma
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.12441

Aims Pyruvate kinase M2 (PKM2) and lactate dehydrogenase 5 (LDH5) 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 PKM2 and LDH5 in TSCC cell lines were determined by Western blot and immunofluorescence. PKM2 and LDH5 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 PKM2 and LDH5 were both significantly higher in TSCC cells than in an immortalized oral epithelial cell line. Overexpression of PKM2 associated significantly with cervical node metastasis (P = 0.0373), while elevated LDH5 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 PKM2 or LDH5 expression displayed significantly reduced overall survival, while patients with tumours overexpressing both proteins showed the worst prognosis with lowest overall survival. Furthermore, PKM2 and LDH5 were identified as independent prognostic predictors for overall patient survival in TSCC. Conclusion Our data indicate that overexpression of PKM2 and LDH5 associates with key clinicopathological features and unfavourable prognosis in TSCC.