Identification of heterogeneity and common characteristics in colorectal carcinoma located in distinct sites

Numerous reports have highlighted distinct clinical and biological characteristics between right-sided and left-sided colon cancers. Despite this research on commonalities and divergences among colorectal cancers (CRC) at different locations remain sparse. In order to elucidate gene expression disparities across various intestinal regions in CRC, we sourced several data series from the Gene Expression Omnibus (GEO) database. We isolated 344 tumor and 54 normal cases spanning seven locations: sigmoid, ascending, caecum, rectum, transverse, descending, and recto-sigmoid. Cell biological functions were assessed utilizing CCK8, EdU assays, Transwell assays, and wound healing assays. We identified location-related differentially expressed genes (DEGs) and their functional enrichment. TNFSF4 exhibited variances between the transverse and descending regions, allowing for discrimination of tumor tissues across four locations (sigmoid, ascending, caecum, and descending) via immune cells. Moreover, we identified 16 hub genes that collectively indicate commonality among the seven different tissue origins. Furthermore, 6 location-related genes, including DCBLD2, GTF3A, GSS, PDK1, TEAD3 and EGR2 were identified for targeted interventions. In vitro experiments indicated that increased GZMB and decreased IER3 reduced CRC cell proliferation, migration, and invasion. In summary, 16 hub genes and 6 location-related genes enhance our understanding of the potential molecular mechanisms underlying CRC spatial heterogeneity. Furthermore, GZMB and IER3 might be potential targets for CRC therapy.