Elevated CELSR3 expression is associated with hepatocarcinogenesis and poor prognosis.

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) shows a cancer-specific expression pattern.
• Hepatocellular carcinoma (HCC) is a significant global health concern with complex molecular underpinnings.

Purpose of the Study:

• To investigate the clinical significance and functional role of CELSR3 in HCC.
• To elucidate the molecular mechanisms underlying CELSR3's involvement in HCC pathogenesis.

Main Methods:

• Analysis of CELSR3 expression in HCC tissues using The Cancer Genome Atlas data.
• Differential expression analysis with edgeR, Pearson correlation for methylation-mRNA association.
• Gene Set Enrichment Analysis (GSEA) to identify affected pathways.
• Integration of differentially expressed mRNAs and microRNA (miRNA) target genes.

Main Results:

• CELSR3 is highly expressed in early-stage HCC and throughout cancer progression, suggesting a role in carcinogenesis.
• Increased CELSR3 expression correlates with methylation levels and is associated with shorter overall survival in HCC patients.
• Pathway analysis revealed enrichment in 'Neuroactive ligand-receptor interaction' and 'Cell cycle' for upregulated genes, and 'Cytokine-cytokine receptor interaction' and 'Metabolic pathways' for downregulated genes.
• The miR-181 family and Wnt/β-catenin signaling pathway were identified as key regulators of CELSR3 expression.

Conclusions:

• CELSR3 plays a crucial role in HCC development and progression.
• CELSR3 expression levels and methylation status are potential prognostic biomarkers for HCC.
• CELSR3 function in HCC is linked to neuroactive ligand-receptor interactions, cell cycle, and immune/metabolic pathways, regulated by miR-181 and Wnt/β-catenin signaling.