Identification of FXYD5 as an oncogene in pediatric papillary thyroid cancer

Papillary thyroid cancer is one of the most common malignancies in pediatrics, with increasing prevalence. We analyzed the single-cell transcriptomic landscape from 11 pediatric patients. The compositions and functions in the tumor microenvironment showed remarkable differences. Endo_tip was primarily from tumor, receiving angiogenesis-associated signals from epithelia. Abundant immune cells infiltrated into tumor. SPP1+ M2-macrophage and tumor cells interacted with T cells via immunosuppressive ligand-receptor pairs. Trajectory inference identified genes in evolutionary branchpoints that may participate in tumor progression. Analyzing the correlation of genes with thyroid differentiation score, clinicopathological features, and prognosis, we identified that FXYD5 might play a key role. RNA-seq data showed FXYD5 mediated proliferation and migration via apoptosis and adhesion processes. Compared with adults, epithelia in pediatrics exhibit higher enrichment in tumor-associated pathways; however, the differences in tumor microenvironment are less pronounced. Our findings reveal a heterogeneous microenvironment of pediatric PTC and identify FXYD5 as a potential prognostic and therapeutic marker.