Irregular expression of FBLN5 has been linked to different forms of cancer. The present study represents the initial investigation into its clinical and functional importance in gastric cancer (GC). Using data from The Cancer Genome Atlas-GC (TCGA-GC) and Gene Expression Omnibus (GEO) databases, we identified differences in FBLN5 expression and examined its association with clinicopathological features. Survival analysis via a Kaplan–Meier plotter evaluated FBLN5’s influence on patient prognosis, while its biological roles were also explored. Furthermore, we developed a GC tissue microarray and conducted immunohistochemical staining for FBLN5 to validate the results. Western blotting was performed in parallel to establish FBLN5 overexpression in GC. We observed that elevated FBLN5 mRNA levels in GC were associated with an unfavorable prognosis. Increased FBLN5 expression showed notable associations with INFc and N3 lymph node metastasis. Both univariate and multivariate analyses identified FBLN5 expression and lymph node metastasis rate as independent prognostic risk factors for GC patients. These factors can be integrated to generate a nomogram for clinical use. Overall, FBLN5 shows a strong association with poorer outcomes in GC patients and serves as a useful prognostic marker.
