A combined computational and functional approach identifies FBLN5 as an amino acid metabolism-related gene and suppressing colorectal cancer progression.

The importance of amino acid metabolism in regulating cancers progression was investigated by accumulating research. But the role of amino acid metabolism-related genes (AAMRGs) played in the colorectal cancer (CRC) progression remains unclear. We used Cox-LASSO analysis to construct an AAMRG prognostic signature and performed Gene set enrichment analysis (GSEA) for further investigation. Moreover, RT‒qPCR was adopted to estimate the expression of AAMRGs in clinical samples. Cell-based assays, including CCK-8, colony formation, and transwell assays were also performed to identify the roles of fibulin 5 (FBLN5) in CRC progression. We established a 10-AAMRG prognostic signature and stratified CRC samples into two risk groups, which showed significant differences in immune infiltration and EMT. RT-qPCR and human protein atlas data confirmed the mRNA and protein expression of these 10 AAMRGs, validating our bioinformatics findings. Importantly, functional assays revealed that FBLN5 overexpression suppressed CRC cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. Our study establishes a novel 10-AAMRG signature as a promising predictor of therapeutic response and prognosis in CRC, and we identify FBLN5 as a pivotal protective factor in CRC progression, offering potential therapeutic value for targeted interventions.