TMEFF2 is a novel prognosis signature and target for endometrial carcinoma

Aims: Tomoregulin-2 (TMEFF2) is a single-pass transmembrane protein whose specific functions and mechanisms in endometrial carcinoma (EC) remain unclear. The aim of this study was to investigate the expression, prognostic role, and potential regulatory mechanisms of TMEFF2 in EC. Materials and methods: The expression and prognosis of TMEFF2 in EC were analyzed via bioinformatics and verified by immunohistochemistry and survival analysis. Proliferation, invasion, and migration of EC cells in vitro were assessed by cell functional assays, while epithelial-mesenchymal transition (EMT) markers and key signaling pathway proteins were evaluated by western blotting. Key findings: The expression of TMEFF2 in EC was significantly higher than that in atypical hyperplasia and normal endometrium, the high expression of TMEFF2 was correlated with advanced stage, poor differentiation, and lymph node metastasis, and also predicted a poor prognosis of EC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMEFF2 and its related genes were enriched in the central nervous system, cell adhesion, signal transduction, and several critical signaling pathways. We also elucidated TMEFF2 networks of kinase, microRNA, and transcription factor targets. In vitro, the proliferation, invasion, and migration abilities of EC cells decreased after TMEFF2 downregulation. Downregulation of TMEFF2 reduced the activation of MAPK and PI3K signaling pathways, and inhibited EMT. Significance: TMEFF2 plays an important role in the initiation, development, and malignant behavior of EC and can be a potential target for early diagnosis and treatment in EC.