Development of a Platelet-Related Prognostic Model for Colorectal Cancer.

Abstract

Colorectal cancer (CRC) represents one of the most common malignancies with high morbidity worldwide. Growing evidence has suggested that platelets are a fundamental component of the tumor microenvironment and play crucial roles in driving tumor biological behavior. The construction of a platelet-related prognostic model that can reliably predict CRC prognosis is of great clinical significance. The 1427 CRC-specific platelet-related genes were collected and mainly enriched in the ribosome and immune-related pathways. Based on platelet-related genes, three subtypes of TCGA CRC samples were identified by consensus clustering and characterized by differences in angiogenesis, epithelial–mesenchymal transition, immune infiltration, and prognosis. A total of 100 prognostic platelet-related genes were identified by univariate Cox regression. LASSO Cox regression further shrank those genes and constructed a 10-gene prognostic model. The patients with higher risk scores had significantly worse disease-specific survival than those with lower scores in both TCGA and validation cohorts. The risk score demonstrated good predictive performance for prognosis by receiver operating characteristic (ROC) curves. Furthermore, multivariate Cox regression analysis showed that the risk score was independent of TNM stage, sex, and age, and a graphic nomogram based on the risk score and clinical factors was developed to predict survival probability of CRC patients. Patients from the high-risk group were characterized by higher infiltration of immunosuppressive cells such as MDSC and Treg and higher expression of checkpoints CTLA4, CD86, and PDCD1LG2. Taken together, we identified three platelet-related subtypes and specifically constructed a promising 10-gene prognostic model in CRC. Our results highlighted the potential survival effects of platelet-related genes and provided evidence about their roles in regulating tumor immunity.