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


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.


CONCLUSIONS
Our data indicate that overexpression of PKM2 and LDH5 associates with key clinicopathological features and unfavourable prognosis in TSCC.
Oral Cancer Center, Institute of Stomatology, Affiliated Stomatological Hospital, Nanjing Medical University, Jiangsu, China; Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital, Nanjing Medical University, Jiangsu, China.
Chunping
C
Yuan
Zhongwu
Z
Li
Yanling
Y
Wang
Bin
B
Qi
Wei
W
Zhang
Jinhai
J
Ye
Heming
H
Wu
Hongbin
H
Jiang
Liang-Nian
LN
Song
Jianrong
J
Yang
Jie
J
Cheng
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D013963:Thyroid Hormones / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology; D000097810:Thyroid Hormone-Binding Proteins
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D008565:Membrane Proteins; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins
LDH5; PKM2; aerobic glycolysis; tongue squamous cell carcinoma