Integrative Single-Cell and Bulk RNA Sequencing Identifies a Macrophage-Related Prognostic Signature for Predicting Prognosis and Therapy Responses in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors, characterized by a high incidence and mortality rate. Macrophages, as a key immune cell type within the tumor microenvironment (TME), play a key role in tumor immune evasion and the progression of CRC. Therefore, identifying macrophage biomarkers is of great significance for predicting the prognosis of CRC patients. This study integrates scRNA-seq and bulk RNA-seq data to identify macrophage-related genes in CRC. By applying a comprehensive machine learning framework, the macrophage-related prognostic signature (MRPS) was constructed by 15 macrophage-related genes with prognostic values. The MRPS demonstrated strong predictive performance across multiple datasets, effectively stratifying high-risk and low-risk patients in terms of overall survival (OS) and disease-specific survival (DSS). Furthermore, immune analysis revealed significant differences between the high-risk and low-risk groups in immune cell infiltration levels and immune checkpoint gene expression patterns. Drug screening identified several small molecules, including Bortezomib and Mitoxantrone, as potential therapeutic options for high-risk patients. Pseudotime trajectory analysis further highlighted the potential role of genes comprising the MRPS in macrophage differentiation. This study provides a powerful tool for personalized prognosis prediction in CRC patients, offering new insights into macrophage-driven mechanisms in tumor progression and potential therapeutic strategies.