Integrated Analysis of Copy Number Variations and Gene Expression Profiling in Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the top three cancer killers worldwide. To identify CNV-driven differentially expressed genes (DEGs) in HBV related HCC, this study integrated analysis of copy number variations (CNVs) and gene expression profiling. Significant genes in regions of CNVs were overlapped with those obtained from the expression profiling. 93 CNV-driven genes exhibiting increased expression in the duplicated regions and 45 showing decreased expression in the deleted regions were obtained, which duplications and deletions were mainly documented at chromosome 1 and 4. Functional and pathway enrichment analyses were performed using DAVID and KOBAS, respectively. They were mainly enriched in metabolic process and cell cycle. Protein-protein interaction (PPI) network was constructed by Cytoscape, then four hub genes were identified. Following, survival analyses indicated that only high NPM1 expression was significantly and independently associated with worse survival and increased recurrence in HCC patients. Moreover, this correlation remained significant in patients with early stage of HCC. In addition, we showed that NPM1 was overexpressed in HCC cells and in HCC versus adjacent non-tumor tissues. In conclusion, these results showed that integrated analysis of genomic and expression profiling might provide a powerful potential for identifying CNV-driven genes in HBV related HCC pathogenesis.