FAM19A5 is an independent prognostic biomarker in thyroid cancer

OBJECTIVES: functional assays. METHODS: RNA sequencing (RNA-seq) data and clinicopathologic characteristics of 513 patients with papillary thyroid cancer (PTC) were retrieved from the Cancer Genome Atlas (TCGA) database and re-analyzed. The diagnostic performance of FAM19A5 was evaluated using receiver operating characteristic (ROC) curve analysis. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-specific survival (DSS). Cox regression analysis was performed to identify independent risk factors for PTC. Gene set enrichment analysis (GSEA) was applied to explore signaling pathways associated with FAM19A5. The mRNA expression of FAM19A5 was detected by quantitative real-time PCR (RT-qPCR). Cell proliferation, migration, and invasion were assessed using colony formation, wound healing, and Transwell assays, respectively. Protein expression of FAM19A5 and nuclear factor kappa B (NF-κB) pathway-related proteins was detected by Western blot. RESULTS: FAM19A5 expression was significantly upregulated in TC tissues and cells. Elevated FAM19A5 expression was correlated with advanced T stage, lymph-node metastasis, and poorer OS and DSS. GSEA showed enrichment of NF-κB signaling pathways in tumors with high FAM19A5 high-expression. FAM19A5 knockdown significantly inhibited TC cell proliferation, migration, and invasion. Furthermore, treatment with tumor necrosis factor alpha (TNF-α), an activator of NF-κB, reversed the inhibitory effects induced by FAM19A5 knockdown. CONCLUSIONS: FAM19A5 is an independent predictor of poor prognosis in TC and may serve as a potential therapeutic target. Mechanistically, FAM19A5 knockdown suppresses TC cell proliferation, migration, and invasion, potentially through modulation of the NF-κB pathway.