Correlation of expression of hypoxia-related proteins with prognosis in oral squamous cell carcinoma patients

Abstract

Introduction: Hypoxia plays a major role in tumor progression, therapy resistance and for prognosis of oral squamous cell carcinoma (OSCC). The crucial step as a response to hypoxia is the activation and stabilization of the alpha subunit of hypoxia inducible factor 1 (HIF-1α). HIF-1: HIF-1 regulates the expression of different genes to adapt the tumor cells to reduced oxygenation. The HIF-1 system is intrinsic regulated by von Hippel-Lindau protein (pVHL). Main downstream proteins are the glucose transporter 1 (GLUT-1), carbonic anhydrase IX (CAIX), and vascular endothelial growth factor (VEGF). For therapeutical stratification in OSCC, it is important to understand the mechanism caused by hypoxic stress and to comprehend the resulting adaptive process in cancer cells. Therefore, an overview of HIF-1α-depending protein expression, focussed on the expression of GLUT-1, CAIX, and VEGF and their prognostic significance in OSCC is given.

Conclusion: Several unique roles of hypoxic pathway in the context of tumor progression are described in this review. As a consequence, a marker panel is proposed to allow a more individualized prognosis in OSCC patients. This marker panel should include beside HIF-1α, pVHL, and GLUT-1.