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 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.