Identifying Molecular Modulators of the Vascular Invasion in Rectal Carcinoma: Role of ADAMTS8 and Its Co-Dependent Genes

Rectal carcinoma (RC) represents approximately 30% of all colorectal carcinomas (CRC) and is considered a distinct clinical entity. Vascular invasion (VI) is recognized as an independent predictor of poor outcomes in RC. In this study, we applied bioinformatics methods to identify gene pathways most likely associated with VI in rectal carcinoma. As <i>ADAMTS8</i> showed statistically significant negative relations with the VI in RC patients, we further analyzed its top co-dependent genes-DNAL4, EVI2B, PPP1R35, PTGR3, RPL21, SOX4, and ZNF3-for the experimentally proven molecular modulators. We identified a total of 23 compounds from the Comparative Toxicogenomics Database based on previously reported data for all eight target genes. The search was expanded to include additional chemical agents by structure similarity using the PubChem database, which revealed 9661 additional compounds. These were subsequently used for molecular interaction analysis against target proteins co-expressed with, or associated with, <i>ADAMTS8</i> in RC with VI. Ultimately, we identified four high-affinity compounds-cyanoginosin LR, doxorubicin, benzo[a]pyrene, and dibenzo(a,e)pyrene-that interacted with all target proteins. These compounds show potential for further assessment of their role in modulating processes related to vascular invasion, which is a strong negative predictor of RC outcomes.