PSMC2 and CXCL8-Modulated Four Critical Gene Biomarkers and Druggable and Vaccinable Targets for Colorectal Cancer

Abstract

AbstractTranscriptomic studies have reported numerous differentially expressed genes in colorectal carcinoma (CRC) versus noncancerous tissues. Given the large number of genes identified, it is unclear which ones are the key genes that drive cancer development. To address the issue, we conducted a large-scale study of eight cohorts with thousands of tumor and nontumor samples, analyzed transcriptomic data, and identified the most miniature set of differentially expressed genes (DEGs) that can nearly perfectly describe the overall features of CRC at the genomic level. The analytical framework was built on a recently proven powerful max-linear competing risk factor model. We first analyzed six public transcriptomic datasets and identified four critical DEGs (i.e., CXCL8, PSMC2, APP, and SLC20A1) with nearly perfect (close to 100%) predictive power. The findings were further validated in a newly collected Chinese cohort and another public dataset. Among the four DEGs, PSMC2 and CXCL8 appeared to play a central role, and CXCL8 alone could serve as a biomarker for early-stage CRC. They rise as druggable and vaccinable targets for CRC. This work represents a pioneering effort to identify critical colorectal-specific genes and their interactions that have not been discovered in previous endeavors.Simple SummaryHuman knowledge of cancer is still limited. There don’t exist reliable genomic biomarkers for cancer diagnosis, and truly functional and druggable genomic (gene) targets haven’t been reported. One of the main reasons is due to lack of powerful discovery tools to discover the best possible and accurate miniature set of genes to fight against the cancer war. Our research was motivated by such an urgent need, and we hope our findings can fill up gaps in the literature and medical practice. We focus on colorectal cancers in this paper.