Elevated CELSR3 expression is associated with hepatocarcinogenesis and poor prognosis

Ouyang,Xiwu; Wang,Zhiming; Yao,Lei; Zhang,Gewen

doi:10.3892/ol.2020.11671

Elevated CELSR3 expression is associated with hepatocarcinogenesis and poor prognosis

Authors:
- Xiwu Ouyang
- Zhiming Wang
- Lei Yao
- Gewen Zhang
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Affiliations: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: May 22, 2020 https://doi.org/10.3892/ol.2020.11671
Pages: 1083-1092
Copyright: © Ouyang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cadherin EGF LAG seven‑pass G-type receptor 3 (CELSR3) has been reported to exhibit a cancer-specific pattern. The present study aimed to investigate the clinical value and functional role of CELSR3 in hepatocellular carcinoma (HCC), and determine the underlying molecular mechanism in patients with HCC. CELSR3 expression in tumor and paracancerous HCC tissues was obtained from The Cancer Genome Atlas. Differential expression analysis was performed using the edgeR package. Pearson correlation analysis was used to analyze the correlation between methylation and mRNA levels of CELSR3. Pathways affected by aberrant CELSR3 expression were identified through Gene Set Enrichment Analysis. The results demonstrated that CELSR3 was highly expressed in the early stage of cancer and was present throughout the entire cancer process, which suggested that CELSR3 may serve a key role in the carcinogenesis of HCC. In addition, upregulation of CELSR3 was associated with its methylation level; high CELSR3 expression indicated a shorter overall survival time. Multiple candidate genes were screened by integrating differentially expressed (DE) mRNAs and target genes of DE microRNAs (miRs). Subsequent pathway enrichment analysis demonstrated that the upregulated genes were predominantly enriched in the ‘Neuroactive ligand‑receptor interaction’ and ‘Cell cycle’ pathways, whereas the downregulated genes were primarily enriched in ‘Cytokine‑cytokine receptor interaction’ and ‘Metabolic pathways’. CELSR3 and its connected nodes and edges were initially removed from the miRNA‑mRNA regulatory network in order to prevent bias and compared with the network containing CELSR3 alone. The frequently dysregulated miRNAs were identified as miR‑181 family members, and the results suggested that miR‑181 and the Wnt/β‑catenin signaling pathway influenced CELSR3 expression.

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