Abstract
ObjectiveHepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients.MethodsThe Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan–Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways.ResultsThe expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype.ConclusionOur results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.
Highlights
Hepatocellular carcinoma (HCC) is currently one of the most common malignant tumors worldwide
Our results indicate that Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients
We divided the expression of CELSR3 in the HCC cell lines into high and low expression groups using the median value, and performed gene set enrichment analysis (GSEA) verification to observe the enrichment of CELSR3 differential expression in the HCC cell lines.The GSEA results were presented in the form of multipleGSEA using the Plyr, grid, gridExtra and ggplot2 packages of R
Summary
Hepatocellular carcinoma (HCC) is currently one of the most common malignant tumors worldwide. The incidence rate is ranked 6th, and the mortality rate is ranked 4th among malignant tumors. There were approximately 840,000 newly diagnosed patients worldwide in 2018, and approximately 780,000 people die annually (Bray et al, 2018). The current treatment methods for HCC have made great progress, strategies for HCC treatment are still limited. Available studies have indicated that some genes are closely related to the prognosis of HCC and might be used as valuable biomarkers for the treatment of this disease (Petrizzo et al, 2018). It is of great importance to search for markers of progression and poor prognosis of HCC
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