A Novel Prognostic Model based on a Coagulation-related Gene Signature for Colorectal Cancer

Abstract

Abstract Background Colorectal cancer (CRC) is a relatively common malignancy worldwide. The diagnosis of CRC at an early stage is difficult due to the lack of effective molecular biomarkers. Consequently, CRC is associated with a high mortality rate. Researchers have shown that coagulation-related factors promote or inhibit CRC progression. The purpose of this study was to identify coagulation-related genes (CRGs) with prognostic value that can potentially serve as therapeutic targets for CRC.Methods In this study, we used data of CRC samples from The Cancer Genome Atlas to identify differentially expressed CRGs. Next, the prognostic model was constructed using Cox proportional hazards regression analysis. The accuracy of the model and survival rate of patients with CRC were analyzed using receiver operating characteristic and Kaplan–Meier curves, respectively. In addition, a nomogram was developed to provide clinical guidance. Subsequently, the model was verified using data from the Gene Expression Omnibus. We evaluated the efficacy of immunotherapy and drug sensitivity using the Tumor Immune Dysfunction and Exclusion algorithms and the Genomics of Drug Sensitivity in Cancer, respectively. The expression of inhibin subunit beta B (INHBB) was knocked down using specific siRNA, and the oncogenic effect of INHBB in colon cancer cells was investigated in vitro.Results We identified seven prognostic CRGs, and constructed a model using five of those (TIMP1, MMP10, WDR72, INHBB, F2RL2). We used the median value to divide patients with CRC into high- and low-risk groups. In The Cancer Genome Atlas cohort, the survival time of patients in the latter group was longer, and the receiver operating characteristic area under curve was ≥ 0.6. The nomogram was successfully constructed. The results of the drug sensitivity analysis suggested that cisplatin, camptothecin, foretinib, tamoxifen, and vinblastine were more effective in the high-risk group versus the low-risk group; the inverse was observed for immunotherapy. Finally, knockdown of INHBB attenuated the proliferation, invasion, and migration of CRC cells in vitro.Conclusion We identified a novel CRG marker in CRC, which may be used as a predictive biomarker and lay the foundation for the personalized treatment of patients with CRC.