Multi-omics analysis links FERMT1 expression to patient survival, immunotherapy response, and metastasis across cancers

Background: Accumulating evidence indicates that fermitin family member 1 (FERMT1) is closely related to various disease processes. However, its association with cancer prognosis, tumor microenvironment (TME), and metastatic progression remains unclear, particularly in lung adenocarcinoma (LUAD). We conducted a comprehensive pan-cancer analysis to evaluate the clinical relevance of FERMT1 expression in LUAD and its functional role in metastasis. Methods: We conducted a multi-omics and functional analysis to evaluate FERMT1 expression across multiple cancer types using 11,069 patient datasets from 33 cancers via The Cancer Genome Atlas (TCGA) database and the University of California, Santa Cruz (UCSC) Xena platform. We assessed FERMT1 expression heterogeneity, prognostic significance, genomic alterations, immune infiltration, and drug sensitivity in pan-cancer and LUAD-specific contexts. Additionally, functional experiments were performed to investigate its role in LUAD cell lines (NCI-H441 and Calu-3). Results: FERMT1 was significantly overexpressed in 13 tumors and downregulated in 3 compared to normal tissues. Its high expression correlated with poor prognosis in multiple cancers and influenced immune cell infiltration. Genomic alterations in FERMT1 were prevalent across cancers. Pan-cancer analysis revealed significant correlations between FERMT1 expression, TME, and stemness scores. In LUAD, FERMT1 expression was significantly associated with tumor T classification (P=0.001) and higher levels in tumor tissues than in normal tissues. Functional assays demonstrated that FERMT1 deletion reduced LUAD cell migration and invasion. Conclusions: FERMT1 serves as a potential biomarker for LUAD prognosis and cancer immunotherapy, highlighting its role in tumor progression and therapeutic response.