Evaluation of hexokinase gene expression in colorectal cancer using bioinformatics tools

Abstract

Disruption of energy metabolism that mainly involves activation of glycolysis that occurs even at the early stages of cancer due to, for example, overexpression of hexokinases such as HK1 and HK2, for the most part represents a universal feature of malignant tumor formation. Overexpression of HK2, which is considered as a marker for a poor prognosis, is commonly believed to take place in colorectal cancer, which is the third in mortality and morbidity among the cancer cases worldwide. The RNA-sequencing data of the Cancer Genome Atlas project (the largest resource in the area of molecular oncology, which contains genomic, transcriptomic, and epigenomic data for thousands of samples of over 20 forms of cancer) were analyzed using the CrossHub software that was developed by the authors, which, on the contrary, revealed the prevalence of reduced levels of HK2 mRNA and only slight changes in the expression of the HK1 gene. The data of transcriptome analysis of colorectal cancer (283 tumor samples and 41 normal tissue samples) were in agreement with the results of the following experimental evaluation of the hexokinase gene expression using the quantitative polymerase chain reaction. Increased mRNA levels of the HK1 and HK2 genes were observed only in a minor part of the samples: 12% for HK1 and 30% for HK2. At the same time a decreased level of the HK2 gene mRNA was found in 50% of the cases. Correlation analysis showed agreement between the changes in the expression of the HK1 and HK2 genes (Spearman’s rank correlation coefficient rS = 0.43, p < 0.001), which can be explained by common deregulation mechanisms of these genes in colorectal tumors. The expression level of the HK3 gene increased significantly in 60% of the samples; it is likely that it was precisely the hexokinase 3 that contributed to the glycolysis activation in colorectal cancer.