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

By Yazhi Sun, Varvara Mironova, Ying Chen, Elliott P.F. Lundh, Qian Zhang, Yuping Cai, Vasilis Vasiliou, Yawei Zhang, Rolando Garcia-Milian, Sajid A Khan, Caroline H. Johnson

Posted 04 Jun 2019
bioRxiv DOI: 10.1101/659151 (published DOI: 10.1016/j.tranon.2019.09.004)

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 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 do. However, women have a higher propensity for RCC than men. Identification of gene expression differences between RCC and LCC is considered a potential means of prognostication. Furthermore, studying colon cancer sidedness 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 cancer using four publicly available annotated datasets housed in the National Center for Biotechnology Information Gene Expression Omnibus (GEO). We identified deferentially expressed genes in tumor tissues from women with RCC, which showed attenuated energy and nutrient metabolism when compared to women with LCC. Specifically, we showed that the downregulation of 5′ AMP-activated protein kinase alpha subunit (AMPKα) and downregulated anti-tumor immune response 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.

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