Construction of a Platelet‐Related Gene Signature for Predicting Prognosis and Drug Sensitivity in Colorectal Cancer

Background Colorectal cancer (CRC) ranks among the most prevalent forms of cancer and is a significant contributor to cancer‐related mortality globally. Platelets play a crucial role in tumor biology by interacting with various immune cells, influencing multiple biological processes. Methods We utilized datasets from TCGA, GSE17536, GSE39582, and GSE103479 to develop a platelet‐related gene signature (PRS) using least absolute shrinkage and selection operator (LASSO) analysis. The effectiveness of PRS in predicting responses to immunotherapy was assessed using three immunotherapy datasets (GSE91061, GSE78220, and IMvigor210) and several predictive scores. Results The PRS demonstrated robust performance in forecasting the survival outcomes of CRC patients. In the TCGA cohort, the areas under the ROC curves for 1‐, 3‐, and 5‐year survival were 0.845, 0.849, and 0.785, respectively. Further analysis identified PRS as an independent risk factor for CRC patients. A nomogram was constructed to predict clinical outcomes for CRC patients. Additionally, a lower PRS score was associated with higher TMB scores, elevated PD1 and CTLA4 immunopheno scores, reduced TIDE and immune escape scores, higher response rates, and more favorable clinical outcomes, suggesting better immunotherapy responses. Conversely, lower PRS scores correlated with increased IC 50 values for certain drugs used in chemotherapy and targeted therapy. Patients in the high‐risk group exhibited elevated gene set scores related to cancer hallmarks such as Notch signaling, hypoxia, and glycolysis. Conclusion Our study established a PRS for CRC that serves as a valuable tool for predicting prognosis, stratifying risk, and guiding treatment decisions for CRC patients.