FLNA Expression in Cancer-Associated Fibroblasts Is Associated with Immunosuppression and Tumor Progression in Colorectal Cancer

Background: The role of Filamin A (FLNA) in colorectal cancer (CRC), particularly within the stromal compartment, remains poorly defined.This study investigates its expression, function, and clinical relevance in CRC. Methods:We integrated transcriptomic data from the GSE39582 training cohort and TCGA/GSE75316 validation cohorts.Analyses included functional enrichment, tumor microenvironment (TME) assessment (ESTIMATE, TIDE), immune correlation, and survival analysis.FLNA's cellular expression was delineated using single-cell RNA-seq data from 27,414 cells.Results: FLNA was upregulated in advanced-stage CRC and exhibited diagnostic potential in microsatellite instability (MSI) samples.Pathway analysis revealed a significant enrichment of FLNA in biological processes implicated in cell adhesion and remodeling of the extracellular matrix.High FLNA expression correlated with an immunosuppressive microenvironment, characterized by elevated stromal/immune scores, increased cancer-associated fibroblast (CAF) and macrophage infiltration, and exclusion of CD8⁺ T cells.It also showed strong associations with multiple immune checkpoints.Single-cell transcriptomics confirmed specific, high FLNA expression in CAFs, fibroblasts, and endothelial cells, where it was associated with pro-tumorigenic functions, including actin cytoskeleton organization.Furthermore, FLNA emerged as an independent predictor of adverse outcomes and was independently associated with reduced overall survival (OS).Conclusion: In summary, our findings suggest that FLNA expression is associated with tumor progression and an immunosuppressive microenvironment in CRC, and that FLNA warrants further investigation as a potential prognostic biomarker and therapeutic target.