Identification of FAT4 Mutation as a Prognostic Marker for Overall Survival and Immune Landscape in Lung Adenocarcinoma

Abstract Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths worldwide. Though many genomic alterations are known, their functional impacts are poorly understood. Methods: We used the TCGA database to study somatic mutations in the FAT4 gene and its correlation with tumor mutation burden (TMB). Differentially expressed genes (DEGs) between FAT4 mutated and wild-type LUAD were identified. Functional enrichment and survival models were constructed using various statistical methods. We also assessed the immune microenvironment and potential therapeutics for high-risk subgroups using the connectivity map (CMap). Results: FAT4 is altered in 15.52% of LUAD cases and correlates with higher TMB. Four genes (TCN1, SCGB3A2, C4BPA, CYP4B1) were identified as prognostic signatures. High-risk subtypes displayed poorer overall survival, higher Macrophage M0 levels, and higher PD-L1 expression. Potential therapeutics targeting PLA2G1B were identified for high-risk subtypes. Conclusion: FAT4 mutations serve as a novel biomarker for LUAD, providing insights into survival and immune microenvironment.