Aberrant expression of Fibulin-5 (FBLN5) has been implicated in multiple cancer types, yet its role in gastric cancer (GC) remains unclear. This study aimed to investigate the clinical and biological significance of FBLN5 in GC. Differential FBLN5 expression and its association with clinicopathological features were analyzed using data from The Cancer Genome Atlas-GC (TCGA-GC) and Gene Expression Omnibus (GEO) databases. The prognostic value of FBLN5 was evaluated using Kaplan–Meier survival analysis, and its functional roles were explored. Furthermore, a gastric cancer tissue microarray was constructed, and FBLN5 expression was validated through immunohistochemistry and Western blotting, confirming its overexpression in GC. High FBLN5 mRNA levels were associated with poor patient outcomes and showed significant correlations with INFc status and N3 lymph node metastasis. Both univariate and multivariate analyses identified FBLN5 expression and lymph node metastasis as independent prognostic factors, which were used to develop a nomogram for clinical application. Collectively, these findings indicate that FBLN5 overexpression is linked to adverse prognosis in GC, highlighting its potential as a prognostic biomarker.
