FNDC1 is closely related to poor prognosis and immune cell infiltration in gastric cancer

Fibronectin type III domain containing 1 (FNDC1) in gastric cancer (GC) progression and immune cell infiltration remains unclear. This study aimed to investigate the impact of FNDC1 on GC progression and to elucidate its association with immune cell infiltration in GC. FNDC1 expression profiles in GC and paired normal tissues were analyzed using datasets from the TCGA, GTEx, and GEO databases, with validation conducted through quantitative real-time PCR (qPCR) and immunohistochemistry (IHC). Differentially expressed genes (DEGs) associated with FNDC1 were identified through gene set enrichment analysis (GSEA) and functional enrichment analysis. We evaluated the role of FNDC1 in GC immune cell infiltration. In addition, Cox regression and Kaplan-Meier analyses were conducted on FNDC1 for its prognostic significance and correlation with clinical variables. We evaluated the role of FNDC1 in gastric cancer cell invasion and migration via Transwell and wound-healing assays following FNDC1 knockdown and overexpression. Finally, survival probabilities in GC patients were predicted by nomogram construction. FNDC1 expression in GC tissues significantly increased relative to that in matched normal samples (P < 0.001), as confirmed by qPCR and IHC (both P < 0.05). There were 359 DEGs associated with ECM Receptor Interaction, Focal Adhesion, and the Degradation of the Extracellular Matrix signaling pathway. FNDC1 expression was positively related to macrophage and NK cells infiltration (macrophage, r = 0.564, P < 0.001; NK cells, r = 0.566, P < 0.001; as validated by IHC and further confirmed by in vitro co-culture assays). Additionally, FNDC1 expression was strongly related to T stage (P < 0.001), pathological stage (P < 0.001), histological grade (P < 0.01), histological type (P < 0.001), anatomic neoplasm subdivision (P < 0.001), and unfavorable overall survival (OS, P < 0.05). In vitro cell experiments indicate that FNDC1 expression is closely associated with the invasion and migration of gastric cancer cells. Our established nomogram effectively predicted the 1-, 3-, and 5-year OS probabilities in patients with GC (C-index [95% CI] = 0.714 [0.689–0.738]). FNDC1 is strongly associated with a dismal prognostic outcome and immune cell infiltration in patients with GC.