Molecular pathway analysis indicates a distinct metabolic and immune phenotype in women with right-sided colon cancer

Abstract

34Colon cancer is the third most commonly diagnosed cancer in the United States. Recent reports 35 have shown that the location of the primary tumor is of clinical importance. Patients with right-36 sided cancers (RCCs) (tumors arising between the cecum and proximal transverse colon) have 37 poorer clinical outcomes than those with left-sided colon cancers (LCCs) (tumors arising 38 between the distal transverse colon and sigmoid colon, excluding the rectum). Interestingly, 39 women have a lower incidence of colon cancer than men do. However, women have a higher 40 propensity for RCC than men. Identification of gene expression differences between RCC and 41 LCC is considered a potential means of prognostication. Furthermore, studying colon cancer 42 sidedness could reveal important predictive markers for response to various treatments. This 43 study provides a comprehensive bioinformatic analysis of various genes and molecular 44 pathways that correlated with sex and anatomical location of colon cancer using four publicly 45 available annotated datasets housed in the National Center for Biotechnology Information's 46 Gene Expression Omnibus (GEO). We identified differentially expressed genes in tumor 47 tissues from women with RCC, which showed attenuated energy and nutrient metabolism when 48 compared to women with LCC. Specifically, we showed that the downregulation of 5' AMP-49 activated protein kinase alpha subunit (AMPKα) and downregulated anti-tumor immune 50 response in women with RCC. This difference was not seen when comparing tumor tissues 51 from men with RCC to men with LCC. Therefore, women with RCC may have a specific 52 metabolic and immune phenotype which accounts for differences in prognosis and treatment 53 response. 54 55