Comprehensive Immune Subtyping and Multi-Omics Profiling of the Tumor Microenvironment in Colorectal Cancer: Implications for Prognosis and Personalized Immunotherapy

作者：Bailing Zhou, Zhiwei Li, Shengxian Fan, Hao Wang, Jihua Wang · 发表于：Current Cancer Drug Targets · 年份：2025 · DOI：10.2174/0115680096395386250910130110 · 被引用次数：2 · 研究领域：Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers、Immune cells in cancer

INTRODUCTION: The Tumor microenvironment (TME) plays a crucial role in colorectal cancer (CRC) prognosis and treatment response. However, comprehensive understandings of TME-related immune subtypes and their mechanisms for precision medicine remain insufficient. This study aims to identify immune subtypes in CRC, develop a prognostic model, and explore the role of microbial diversity in tumor progression. METHODS: Multi-omics data and non-negative matrix factorization (NMF) were used to classify CRC into immune subtypes. Differentially expressed TME-related genes were identified, and a prognostic risk model was developed using Cox and LASSO regression. Single-cell RNA sequencing (scRNA-seq) assessed cellular interactions and gene set variations. Microbiome profiling was integrated to evaluate the impact of microbial diversity on CRC progression and immune modulation. Key findings were validated using immunohistochemistry, external datasets, and qPCR in patient-derived organoids. RESULTS: Four TME-related immune subtypes were identified: immune-exhausted C1 (poor prognosis, high immune infiltration), immune-activated C2/C3 (better prognosis), and immune-desert C4 (worst prognosis). A risk model based on genes (SOX9, CLEC10A, RAB15, RAB6B, PCOLCE2, FUT1) stratified patients into high- and low-risk groups. High-risk groups exhibited increased Enterobacteriaceae and Clostridium, while low-risk groups showed higher Porphyromonadaceae and Peptostreptococcaceae, correlating with bet...