Dachsous cadherin related 1 (DCHS1) is a novel biomarker for immune infiltration and epithelial- mesenchymal transition in endometrial cancer via pan-cancer analysis

Abstract

Background Dachsous cadherin related 1 (DCHS1) is one of calcium-dependent adhesion membrane proteins and is mainly involved in the development of mammalian tissues. There is a lack of more detailed research on the biological function of DCHS1 in pan-cancer. Materials and methods We evaluated the expression, the prognostic value, the diagnostic value and genomic alterations of DCHS1 by using the databases, including TCGA, UALCAN, HPA, GEPIA2.0 and GSCA. We employed the databases of UCSC, TIMER2.0, TISIDB, GSCA to analyze the association between DCHS1 expression and the immune microenvironment, stemness, TMB, MSI and anticancer drug sensitivity. BioGRID, STRING and GEPIA2.0 were used to perform protein interaction and functional enrichment analysis. Real-time quantitative PCR, CCK8, Transwell assay and WB were performed to determine the function of DCHS1 in UCEC. Results DCHS1 is differentially expressed in many cancers and its expression is significantly associated with tumor prognosis and diagnosis. DCHS1 expression was significantly correlated with the infiltration of cancer-associated fibroblasts (CAFs) and Endothelial cell (ECs), and Hematopoietic stem cell in most cancers. In addition, DCHS1 was significantly associated with sensitivity to many antitumor drugs. Functional enrichment analysis revealed that DCHS1-related proteins were involved in Focal adhesion, Endometrial cancer and Wnt signaling pathway. GSEA results showed that DCHS1 is related to epithelial-mesenchymal transition (EMT) in many cancers. In vitro experiments in UCEC showed that silencing of DCHS1 blocked cell proliferation, migration and EMT. Conclusions Our findings indicated that DCHS1 might be a novel prognostic and diagnostic biomarker and immunotherapy target, and plays an important role in the proliferation, migration and EMT in UCEC.