Comprehensive Analysis of a Platelet- and Coagulation-Related Prognostic Gene Signature Identifies CYP19A1 as a Key Tumorigenic Driver of Colorectal Cancer

Abstract

Background: The intricate interplay between the platelet-coagulation system and the progression of malignant tumors has profound therapeutic implications. However, a thorough examination of platelet and coagulation markers specific to colorectal cancer (CRC) is conspicuously absent in the current literature. Consequently, there is an urgent need for further exploration into the mechanistic underpinnings of these markers and their potential clinical applications. Methods: By integrating RNA-seq data and clinicopathological information from patients with CRC in the cancer genome atlas, we identified genes related to the platelet-coagulation system using weighted gene co-expression networks and univariate Cox analysis. We established a prognostic risk model based on platelet- and coagulation-related genes using Lasso Cox regression analysis and validated the model in two independent CRC cohorts. We explored potential biological functional disparities between high-risk and low-risk groups through comprehensive bioinformatics analysis. Results: Our findings indicate that colorectal cancer patients classified as high-risk generally exhibit poorer prognoses. Moreover, the model’s risk scores were associated with the differential composition of the immune tumor microenvironment, suggesting its applicability to infer immunotherapy responsiveness. Cellular functional experiments and animal experiments indicated that CYP19A1 expression in CRC influences malignant phenotype and platelet activation. Conclusions: In summary, we present a novel platelet- and coagulation-related risk model for prognostic assessment of patients with CRC and confirm the important role of CYP19A1 in promoting malignant progression of CRC.

Keywords

• colorectal cancer
• coagulation
• platelet
• CYP19A1
• weighted gene co-expression network analysis
• single-cell sequencing