Systematic expression analysis of the CELSR family reveals the importance of CELSR3 in human lung adenocarcinoma.

ABSTRACT

Cadherin EGF LAG seven-pass G-type receptors (CELSRs) are involved in the progression of various types of cancer. CELSR3, a crucial signalling molecule in the WNT/PCP pathway, is believed to be associated with tumorigenesis and metastasis. However, its role in lung adenocarcinoma (LUAD) remains unclear. In this paper, we analysed the expression of CELSR family members using the Oncomine, GEPIA and UALCAN databases. We used a Kaplan-Meier plotter to assess the effect of CELSRs on tumour prognosis. Next, gene ontology (GO), KEGG pathway, miRNA target, kinase target and transcription factor-target enrichment were analysed by GSEA. Simultaneously, we conducted functional assays including cell viability, colony formation and transwell assays, to determine the oncogenic role of CELSR3 in LUAD. Finally, we used the TIMER and TISIDB databases to analyse the correlation between CELSR3 and immune infiltration and the potential chemokine receptor axis causing immune cell expression. High expression of CELSR3 is in LUAD predicts poor prognosis and early progression of the tumour. KEGG and GO enrichment analysis revealed the functional relationship between CELSR3 and cell adhesion, the cell cycle, and DNA replication. Down-regulation of CELSR3 suppressed cell proliferation to a significant extent, in addition to inhibiting invasion and migration in LUAD cells. Finally, CELSR3 expression was significantly correlated with the infiltration level of CD8+T cells through the CCL17/CCR4 axis in LUAD. These results indicate that CELSR3 can serve as a prognostic biomarker for determining prognosis and immune infiltration in LUAD.