Calumenin contributes to epithelial-mesenchymal transition and predicts poor survival in glioma

Abstract

Background ‒ Calumenin (CALU) has been reported to be associated with invasiveness and metastasis in some malignancies. However, in glioma, the role of CALU remains unclear. Methods ‒ Clinical and transcriptome data of 998 glioma patients, including 301 from CGGA and 697 from TCGA dataset, were included. R language was used to perform statistical analyses. Results ‒ CALU expression was significantly upregulated in more malignant gliomas, including higher grade, IDH wildtype, mesenchymal, and classical subtype. Gene Ontology analysis revealed that CALU-correlated genes were mainly enriched in cell/biological adhesion, response to wounding, and extracellular matrix/structure organization, all of which were strongly correlated with the epithelial-mesenchymal transition (EMT) phenotype. GSEA further validated the profound involvement of CALU in EMT. Subsequent GSVA suggested that CALU was particularly correlated with three EMT signaling pathways, including TGFβ, PI3K/AKT, and hypoxia pathway. Furthermore, CALU played synergistically with EMT key markers, including N-cadherin, vimentin, snail, slug, and TWIST1. Survival and Cox regression analysis showed that higher CALU predicted worse survival, and the prognostic value was independent of WHO grade and age. Conclusions ‒ CALU was correlated with more malignant phenotypes in glioma. Moreover, CALU seemed to serve as a pro-EMT molecular target and could contribute to predict prognosis independently in glioma.