FLNA Expression in Cancer-Associated Fibroblasts Is Associated with Immunosuppression and Tumor Progression in Colorectal Cancer.
- 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300000, China.
- 2Department of Gastrointestinal Surgery II, Handan First Hospital, Handan 056000, China.
Abstract
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.
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BibTeX
@article{yao2026flna,
title = {{FLNA Expression in Cancer-Associated Fibroblasts Is Associated with Immunosuppression and Tumor Progression in Colorectal Cancer.}},
author = {Qianze Yao and Ningbo Liu and Shilong Li and Bang Liu and Guozheng Ding and Hengbin Zhao and Weihua Fu},
journal = {Journal of Cancer},
year = {2026},
month = oct,
doi = {10.7150/jca.134223},
url = {https://europepmc.org/article/MED/42910128},
note = {CC BY},
}
RIS
TY - JOUR
TI - FLNA Expression in Cancer-Associated Fibroblasts Is Associated with Immunosuppression and Tumor Progression in Colorectal Cancer.
AU - Qianze Yao
AU - Ningbo Liu
AU - Shilong Li
AU - Bang Liu
AU - Guozheng Ding
AU - Hengbin Zhao
AU - Weihua Fu
PY - 2026
DA - 2026/10/16
JO - Journal of Cancer
DO - 10.7150/jca.134223
UR - https://europepmc.org/article/MED/42910128
AB - 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.
SN - 1837-9664
ER -