The Role of Glucose Transporters in Oral Squamous Cell Carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy associated with a poor prognosis. The Warburg effect can be observed in OSCCs, with tumours requiring a robust glucose supply. Glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs) are overexpressed in multiple malignancies, and are correlated with treatment resistance, clinical factors, and poor overall survival (OS). We conducted a systematic review to evaluate the differences in GLUT/SGLT expression between OSCC and normal oral keratinocytes (NOK), as well as their role in the pathophysiology and prognosis of OSCC. A total of 85 studies were included after screening 781 papers. GLUT-1 is regularly expressed in OSCC and was found to be overexpressed in comparison to NOK, with high expression correlated to tumour stage, treatment resistance, and poor prognosis. No clear association was found between GLUT-1 and tumour grade, metastasis, and fluorodeoxyglucose (FDG) uptake. GLUT-3 was less thoroughly studied but could be detected in most samples and is generally overexpressed compared to NOK. GLUT-3 negatively correlated with overall survival (OS), but there was insufficient data for correlations with other clinical factors. Expression of GLUT-2/GLUT-4/GLUT-8/GLUT-13/SGLT-1/SGLT-2 was only evaluated in a small number of studies with no significant differences detected. GLUTs 7 and 14 have never been evaluated in OSCC. In conclusion, the data demonstrates that GLUT-1 and GLUT-3 have a role in the pathophysiology of OSCC and represent valuable biomarkers to aid OSCC diagnosis and prognostication. Other GLUTs are comparatively understudied and should be further analysed because they may hold promise to improve patient care.