An Activated Dendritic-Cell-Related Gene Signature Indicative of Disease Prognosis and Chemotherapy and Immunotherapy Response in Colon Cancer Patients

Abstract

Accumulating evidence has underscored the prognostic value of tumor-infiltrating immune cells in the tumor microenvironment of colon cancer (CC). In this retrospective study, based on publicly available transcriptome profiles and clinical data from the Gene Expression Omnibus and The Cancer Genome Atlas databases, we derived and verified an activated dendritic cell (aDC)-related gene signature (aDCRS) for predicting the survival outcomes and chemotherapy and immunotherapy response of CC patients. We quantified the infiltration abundance of 22 immune cell subtypes via the “CIBERSORT” R script. Univariate Cox proportional hazards (PHs) regression was used to identify aDC as the most robust protective cell type for CC prognosis. After selecting differentially expressed genes (DEGs) significantly correlated with aDC infiltration, we performed univariate Cox-PH regression, LASSO regression, and stepwise multivariate Cox-PH regression successively to screen out prognosis-related genes from selected DEGs for constructing the aDCRS. Receiver operating characteristic (ROC) curves and Kaplan–Meier (KM) analysis were employed to assess the discriminatory ability and risk-stratification capacity. The “oncoPredict” package, Cancer Treatment Response gene signature DataBase, and Tumor Immune Dysfunction and Exclusion algorithm were utilized to estimate the practicability of the aDCRS in predicting response to chemotherapy and immune checkpoint blockade. Gene set enrichment analysis and single-cell RNA sequencing analysis were also implemented. Furthermore, an aDCRS-based nomogram was constructed and validated via ROC curves, calibration plots and decision curve analysis. In conclusion, aDCRS and an aDCRS-based nomogram will facilitate precise prognosis prediction and individualized therapeutic interventions, thus improving the survival outcomes of CC patients in the future.