FGFR Like1 drives esophageal cancer progression via EMT , PI3K /Akt, and notch signalling: insights from clinical data and next‐generation sequencing analysis

FGFRL1, one of the least explored FGFRs, has recently been shown to have implications in cancer, but its functional significance in esophageal cancer (EC) remains largely unexplored. We evaluated FGFRL1 expression in EC patients (n = 106) using immunohistochemistry, observing a significant increase in preneoplastic and neoplastic tissues (P < 0.001, OR = 73.2; AUC = 0.817). RNAi-coupled next-generation sequencing revealed enrichment of EMT, PI3K/Akt, and Notch pathways. Quantitative RT-PCR validated the downregulation of top cluster and Notch pathway genes (P < 0.05). Western blot showed decreased phospho-GSK3β, phospho-Akt, and mesenchymal markers. TCGA data supported a positive correlation with EMT. Functional assays demonstrated FGFRL1's oncogenic role, showing G1 phase arrest, and reduced proliferation, migration, and invasion (P < 0.001). Our study highlights FGFRL1 as a key driver of EC progression.