FAP as a Clinical Biomarker: FAP+ CAFs Orchestrate an Immunosuppressive Stem Cell Niche via the COL1A1/2-CD44 Axis in Colon Cancer

作者：Ding Q, Lu Q · 发表于：Stem cells international · 年份：2026 · DOI：10.1155/sci/4678145 · 被引用次数：31 · 研究领域：CD44、cancer stem cells、cancer-associated fibroblasts、colon cancer、fibroblast activation protein、immunosuppressive microenvironment

BACKGROUND: Colon cancer (CC) remains a leading cause of cancer-related mortality worldwide, driven largely by the complex interactions within the tumor microenvironment (TME). Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) and is associated with poor prognosis, yet its role in coordinating immune evasion and cancer stemness remains to be fully elucidated. METHODS: We integrated multiomics data from TCGA and GEO databases, utilizing bulk RNA-seq and single-cell RNA-seq (scRNA-seq) analyses. Findings were validated via tissue microarray (TMA) immunohistochemistry (IHC). We further employed cell-cell communication analysis, pseudotime trajectory modeling, and the Connectivity Map (CMap) for drug sensitivity prediction and molecular docking. RESULTS: FAP was significantly upregulated in CC tissues and correlated with advanced clinical stages. scRNA-seq confirmed that FAP is predominantly expressed in CAFs. Functional analysis revealed that FAP-high tumors are enriched in extracellular matrix (ECM) remodeling and immunosuppressive pathways. Cell-cell communication analysis identified that FAP+ CAFs interact with T cells and cancer stem cells (CSCs) primarily through the COL1A1/2-CD44 axis. Specifically, FAP+ CAFs promote the differentiation of naive T cells into regulatory T cells (Tregs) and are positively correlated with various stemness markers, including CD44, ABCG2, and BMI1. Based on these findings, we established a 14-gene...