Effect of FLRT3 on epithelial-mesenchymal transition in clear cell renal cell carcinoma

Objective: FLRT3 is a member of the fibronectin leucine-rich transmembrane protein family, which regulates cell-cell adhesion and epithelial-mesenchymal transition (EMT). However, the role of FLRT3 in clear cell renal cell carcinoma (ccRCC) remains unknown; therefore, we explored the potential role of FLRT3 in ccRCC. Methods: We analyzed FLRT3 expression levels in ccRCC tissues across multiple databases. We examined the relationship between FLRT3 expression and EMT through single-cell data and transcriptional regulatory network analyses. Additionally, we investigated the association between FLRT3 expression levels and various clinicopathological indicators, compared the impact of FLRT3 expression on patient prognosis, and constructed a nomogram prognostic model. Furthermore, we performed enrichment analyses on differentially expressed genes to reveal potential biological functions and mechanisms. Results: FLRT3 expression levels were significantly lower in ccRCC tissues compared to normal kidney tissues and progressively decreased with advancing pathological stages and grades. FLRT3 mediated the promotion of EMT by transcription factor ATF4; survival analysis indicated that patients with high FLRT3 expression had significantly better overall survival compared to those with low FLRT3 expression. Enrichment analysis revealed that FLRT3 was associated with epithelial cell differentiation, retinol metabolic processes, and collagen-containing extracellular matrix. Conclusion: FLRT3 expression is downregulated in ccRCC and may promote EMT through transcription factor ATF4. Downregulation of FLRT3 is associated with poor prognosis.