Abstract
BACKGROUND: Complement Factor H (CFH) has been reported as an indispensable role in innate and adaptive immunity. Despite increasing interest in CFH, its clinicopathological implications and immunological mechanisms across different cancers remain unclear and are currently under debate. METHODS: Investigating the function of CFH in 23 tumor types using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Tumor Immune Estimation Resource 2.0 (TIMER2.0) database, cBioportal, Human Protein Atlas (HPA). Then using Cell Counting Kit-8 (CCK8) assay, plate colony formation assay, and wound healing assay to detect the biological function of CFH in vitro. RESULTS: CFH exhibited dysregulated expression across multiple cancers, with associations observed between its expression levels, immune cell infiltration, clinical stage, and immune subtype. Additionally, CFH was critically involved in shaping the tumor microenvironment and regulating immune responses. The upregulated expression level of CFH was significantly related to tumor-infiltrating immune cells (TICs), tumor mutational burden (TMB), and microsatellite instability (MSI). Functionally, we found that knockdown of CFH could inhibit the tumor cell proliferation and invasion. CONCLUSIONS: This study implies the potential prognostic and immunological role of CFH in various cancers, and CFH could act as a biomarker for tumor immunotherapy.