COPB2: A Novel Prognostic Biomarker That Affects Progression of HCC

This study is aimed at investigating the expression, underlying biological function, and clinical significance of coatomer protein complex subunit beta 2 (COPB2) in hepatocellular carcinoma (HCC).

HCC-related data were extracted from The Cancer Genome Atlas (TCGA) database, International Cancer Genome Consortium (ICGC) database, and Gene Expression Omnibus (GEO) database. A logistic regression module was applied to analyze the relationship between the expression of COPB2 and clinicopathologic characteristics. The Cox proportional hazard regression model and Kaplan-Meier method were used for survival analysis. Gene set enrichment analysis (GSEA) was used to annotate the underlying biological functions. Loss-of-function experiments were conducted to determine the underlying mechanisms.

COPB2 was overexpressed in HCC, and high expression of COPB2 was significantly correlated with higher alpha fetoprotein (AFP) (odds ratio (OR) = 1.616, >20 vs. ≤20, p < 0.05), stage (OR = 1.744, III vs. I, p < 0.05), and grade (OR = 1.746, G4+G3 vs. G2+G1, p < 0.05). Kaplan-Meier survival analysis showed that HCC patients with high COPB2 expression had a worse prognosis than those with low COPB2 expression (p < 0.0001 for TCGA cohort, p < 0.05 for ICGC cohort). The univariate Cox (hazard ratio (HR) = 1.068, p < 0.0001) and multivariate Cox (HR = 2.011, p < 0.05) regression analyses suggested that COPB2 was an independent risk factor. GSEA showed that mTOR and other tumor-related signaling pathways were differentially enriched in the high COPB2 expression phenotype. Silencing of COPB2 inhibited the proliferation, migration, and invasion abilities by suppressing epithelial-mesenchymal transition and mTOR signaling.

COPB2 is a novel prognostic biomarker and a promising therapeutic target for HCC.