Integrating scRNA-seq and bulk RNA-seq to characterize infiltrating cells in the colorectal cancer tumor microenvironment and construct molecular risk models

Colorectal cancer (CRC) is a malignancy that is both highly lethal and heterogeneous. Although the correlation between intra-tumoral genetic and functional heterogeneity and cancer clinical prognosis is wellestablished, the underlying mechanism in CRC remains inadequately understood. Utilizing scRNA-seq data from GEO database, we re-isolated distinct subsets of cells, constructed a CRC tumor-related cell differentiation trajectory, and conducted cell-cell communication analysis to investigate potential interactions across cell clusters. A prognostic model was built by integrating scRNA-seq results with TCGA bulk RNA-seq data through univariate, LASSO, and multivariate Cox regression analyses. Eleven distinct cell types were identified, with Epithelial cells, Fibroblasts, and Mast cells exhibiting significant differences between CRC and healthy controls. T cells were observed to engage in extensive interactions with other cell types. Utilizing the 741 signature genes, prognostic risk score model was constructed. Patients with high-risk scores exhibited a significant correlation with unfavorable survival outcomes, high-stage tumors, metastasis, and low responsiveness to chemotherapy. The model demonstrated a strong predictive performance across five validation cohorts. Our investigation involved an analysis of the cellular composition and interactions of infiltrates within the microenvironment, and we developed a prognostic model. This model provides valuable insights into the prognosis and therapeutic evaluation of CRC.