Distinct regulation mechanism of immune-related genes in left-sided and right-sided colon cancer

Colon cancer is one of the most common cancers in worldwide. Emerging evidence has demonstrated distinct patterns of immune infiltration between left colon cancer (LCC) and right colon cancer (RCC), classified according to primary tumor location. However, the underlying mechanism was still unknown. Here, we identified 111 more up-regulated genes (MURGs) including PD1 (PDCD1) and CTLA4 in RCC and 166 more down-regulated genes (MDRGs) in LCC, all participating in immune-related biological processes. Notably, CD83, CXCR4 and ISL1 emerged as reversely regulated immune-related genes (IRGs) showing opposite regulation patterns between the two cancer types. Through regulatory network analysis, we found that genetic mutations predominantly drive enhanced immune infiltration in RCC through IRG up-regulation, whereas DNA methylation-mediated IRG suppression accounts for diminished immune responses in LCC. Furthermore, prognostic models based on these IRGs with high-quality were constructed in LCC and RCC respectively. In conclusion, our results provide crucial insights into the divergent immunoregulatory mechanisms governing LCC and RCC, potentially facilitating the discovery of novel biomarkers for prognosis prediction and targeted therapy.