GLUT-1(+)/TKTL1(+) coexpression predicts poor outcome in oral squamous cell carcinoma.

OBJECTIVE: Tumor hypoxia is a crucial negative prognostic factor associated with outcome of oral squamous cell carcinoma (OSCC). STUDY DESIGN: Expression of glucose transporter 1 (GLUT-1) (solute carrier family 2 [facilitated glucose transporter], member 1 [SLC2A1]) was analyzed in OSCC specimen (n = 161) and cancer cell lines by immunohistochemistry and Western blotting. GLUT-1 expression on protein level was correlated with transketolase-like 1 (TKTL1) expression, clinical characteristics, and effect on survival. Subgroup analysis was performed for GLUT-1/TKTL1 coexpression. RESULTS: GLUT-1 expression was significantly correlated with TKTL1 expression (P < .0001) and recurrence of the tumor (P = .001). Multivariate analysis did not find GLUT-1 expression to be an independent prognostic factor (P = .2478). GLUT-1(+)/TKTL1(+) subgroup showed the worst effect on survival compared with the GLUT-1(-)/TKTL1(-) subgroup (P = .0002). CONCLUSIONS: This study provides evidence that tumors linked with combined enhanced glucose uptake (GLUT-1(+)) and hypoxia-related glucose metabolism (TKTL1(+)) characteristics (GLUT-1(+)/TKTL1(+) coexpression) are associated with shorter survival in OSCC.

A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells.

BACKGROUND: Biomarkers allowing the characterization of malignancy and therapy response of oral squamous cell carcinomas (OSCC) or other types of carcinomas are still outstanding. The biochemical suicide molecule endonuclease DNaseX (DNaseI-like 1) has been used to identify the Apo10 protein epitope that marks tumor cells with abnormal apoptosis and proliferation. The transketolase-like protein 1 (TKTL1) represents the enzymatic basis for an anaerobic glucose metabolism even in the presence of oxygen (aerobic glycolysis/Warburg effect), which is concomitant with a more malignant phenotype due to invasive growth/metastasis and resistance to radical and apoptosis inducing therapies. METHODS: Expression of Apo10 and TKTL1 was analysed retrospectively in OSCC specimen (n = 161) by immunohistochemistry. Both markers represent independent markers for poor survival. Furthermore Apo10 and TKTL1 have been used prospectively for epitope detection in monocytes (EDIM)-blood test in patients with OSCC (n = 50), breast cancer (n = 48), prostate cancer (n = 115), and blood donors/controls (n = 74). RESULTS: Positive Apo10 and TKTL1 expression were associated with recurrence of the tumor. Multivariate analysis demonstrated Apo10 and TKTL1 expression as an independent prognostic factor for reduced tumor-specific survival. Apo10+/TKTL1+ subgroup showed the worst disease-free survival rate in OSCC.EDIM-Apo10 and EDIM-TKTL1 blood tests allowed a sensitive and specific detection of patients with OSCC, breast cancer and prostate cancer before surgery and in after care. A combined score of Apo10+/TKTL1+ led to a sensitivity of 95.8% and a specificity of 97.3% for the detection of carcinomas independent of the tumor entity. CONCLUSIONS: The combined detection of two independent fundamental biophysical processes by the two biomarkers Apo10 and TKTL1 allows a sensitive and specific detection of neoplasia in a noninvasive and cost-effective way. Further prospective trials are warranted to validate this new concept for the diagnosis of neoplasia and tumor recurrence.