Hexokinase II expression is correlated with colorectal cancer prognosis

Abstract

Enhanced glycolysis is observed during tumorigenesis, with an upregulation in key glycolytic enzymes. Hexokinase II (HKII) catalyzes the first irreversible step of glycolysis and is often overexpressed in tumors. Abnormal vasculature within tumors leads to regional ischemic conditions that promote tumor progression. The aims of this study were to assess the expression of HKII in colorectal cancer tissues, and to correlate HKII expression with clinical parameters and patient outcome. Sections from 60 FFPE primary colorectal cancer tumor samples were dual fluorescence immunostained for HKII and carbonic anhydrase IX (CAIX; serving as an ischemic marker) and assessed using semi-quantitative immunofluorescence. Associations of HKII and CAIX levels with patient characteristics, tumor pathology and clinical outcome were studied using univariate analysis. HKII expression was found in neoplastic cells of non-ischemic regions of tumors and within the tumor stroma. CAIX expression was found primarily in neoplastic cells, and was associated with patient age (OR=4.04, ≥70 vs. <70). Tumor samples scoring lower for HKII were associated with early disease progression (p=0.0155) and poor overall survival (p=0.0248). Interestingly, tumor samples that presented with stromal HKII staining were associated with early disease progression (p=0.0485) and poor overall survival (p=0.0235). We identified low overall HKII expression to be associated with the outcome of colon cancer. However, the correlation between stromal HKII expression and worse survival in colorectal cancer patients warrant further investigation. This study assessed the prognostic value of hexokinase II expression in colorectal cancer. In total, 60 FFPE primary colorectal cancer tumor samples were immunostained and correlated with patient characteristics, tumor pathology and clinical outcome. Interestingly, low overall HKII expression was correlated with worse patient outcome. Separately, stromal HKII staining was correlated with worse patient outcome.