Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer

Abstract

Colon cancer is the third most commonly diagnosed cancer in the United States. Recent reports have shown that the location of the primary tumor is of clinical importance. Patients with right-sided colon cancers (RCCs) (tumors arising between the cecum and proximal transverse colon) have poorer clinical outcomes than those with left-sided colon cancers (LCCs) (tumors arising between the distal transverse colon and sigmoid colon, excluding the rectum). Interestingly, women have a lower incidence of colon cancer than men, but have a higher propensity for RCC. The reason for this difference is not known; however, identification of sex-specific differences in gene expression by tumor anatomical location in the colon could provide further insight. Moreover, it could reveal important predictive markers for response to various treatments. This study provides a comprehensive bioinformatic analysis of various genes and molecular pathways that correlated with sex and anatomical location of colon cancers using four publicly available annotated data sets housed in the National Center for Biotechnology Information's Gene Expression Omnibus. We identified differentially expressed genes in tumor tissues from women with RCC, which showed attenuated energy and nutrient metabolism when compared with women with LCC. Specifically, we showed the downregulation of 5′ AMP-activated protein kinase alpha subunit (AMPKα) and anti-tumor immune responses in women with RCC. This difference was not seen when comparing tumor tissues from men with RCC to men with LCC. Therefore, women with RCC may have a specific metabolic and immune phenotype which accounts for differences in prognosis and treatment response.