Integrated single-cell and bulk tissue analyses reveal distinct macrophage subtypes and a candidate prognostic signature in colorectal cancer: implications for tumor immune characterization

Introduction Colorectal cancer (CRC) represents a major global health burden, marked by high morbidity and mortality rates that place a considerable strain on healthcare systems. Methods This study leveraged integrated bioinformatic analyses, single-cell RNA sequencing, and clinical sample validation to investigate the role of macrophage-related genes (MRGs) in CRC, with the goal of deepening our understanding of the complex interplay within the tumor microenvironment. Results Differential expression analysis comparing CRC tumor and normal tissues in the TCGA-COADREAD cohort identified 1,962 differentially expressed genes (DEGs). In parallel, a predefined set of 1,719 MRGs was curated from public databases and the literature to define the macrophage-related biological context. By integrating the bulk transcriptomic DEGs, single-cell macrophage subtype-specific genes, and the predefined MRG set, we identified eight hub macrophage-related DEGs (MRDEGs) implicated in CRC. Functional enrichment analysis of these eight MRDEGs revealed significant roles in immune-regulatory processes, including leukocyte chemotaxis, eosinophil chemotaxis, chemokine receptor binding, and the chemokine signaling pathway. From these eight hub MRDEGs, we selected CCL24 and MMP12 via LASSO-Cox regression to construct a prognostic risk model. Immune infiltration analysis using CIBERSORT revealed significant differences ( p p Discussion This study provides a candidate prognostic stratification model that requires further validation in independent cohorts and prospective studies, offering a macrophage-related prognostic clue for future investigations.