Novel prognostic model of complement and coagulation cascade-related genes correlates with immune environment and drug sensitivity in hepatocellular carcinoma.

Introduction: Hepatocellular carcinoma (HCC) is an immunogenic cancer characterized by high morbidity and mortality rates. The complement and coagulation systems are traditionally associated with the incidence of thrombotic complications and complement activation in cancer. However, the prognostic value of complement and coagulation-related factors (CCCR) in HCC remains undetermined. This study aims to construct a prognostic model based on the complement and coagulation cascades to evaluate its potential for immunotherapy and its relationship with drug sensitivity. Materials and methods: We comprehensively investigated the expression profiles of CCCR genes using the TCGA, ICGC, and GTEx databases. Cox proportional hazards regression models were employed to assess prognostic value. Results: This study presents a novel prognostic model derived from the comprehensive analysis of nine CCCR genes (C1S, C6, C7, F11, F13B, F7, SERPINE1, SERPINF2, and SERPING1) to elucidate their correlation with the tumor immune environment and drug sensitivity in patients with HCC. Our model stratified patients into high- and low-risk groups based on distinct survival outcomes. The area under the curve (AUC) values of the risk score for one-, two-, and three-year survival rates were all greater than 0.660. Additionally, we analyzed immune cell infiltration patterns, revealing a strong correlation between CCCR gene expression and the immune microenvironment, including T cell and macrophage activity. Our findings also identified potential therapeutic targets, demonstrating differential drug sensitivity profiles between the risk groups. JAK1_8709_1718 was found to be more suitable for patients with low-risk HCC. Conclusion: Our findings provide promising insights into the clinical relevance of CCCR genes as prognostic markers and therapeutic targets. This study underscores the significance of CCCR in HCC and paves the way for improved therapeutic strategies.