Abstract: Objective To explore the effect of copy number variation on the occurrence and development of hepatocellular carcinoma by using copy number variation and transcriptome experiment of hepatocellular carcinoma combined with public clinical data. Methods The copy number variation found in hepatoma cell lines HepG2 and Huh7 was identified by optical genome mapping. The function of the copy number variant genes in the two cell lines was analyzed, and the protein interaction network was mapped according to the enrichment pathway. Key genes in the core network of two cell lines were selected to analyze the relationship between copy number variation and gene expression in hepatocellular carcinoma. The relationship between gene expression and clinical survival was analyzed by GEPIA database. RNA-seq assay and public data were used to verify gene expression levels. Results HepG2 cells mainly showed increased copy number, and related genes were enriched in estrogen signaling pathway and Staphylococcus aureus infection pathway. Huh7 cells showed both increased and decreased copy number, and related genes mainly concentrated in olfactory conduction and cytokine-cytokine receptor interaction pathways. The copy number of key genes SRC, MAPK3 and MAP3K7 was proportional to gene expression, and survival was significantly reduced in patients with high expression of these genes (P＜0.05). Compared with HEK293T cell line, the expression of SRC and MAP3K7 genes in the two hepatocellular carcinoma lines was significantly increased(P＜0.001), suggesting the specific variation of hepatocellular carcinoma. MAPK3 had no difference. Conclusions The expression of copy number variant genes SRC and MAP3K7 in hepatocellular carcinoma is significantly correlated with the prognosis of patients, and may significantly affect the development and heterogeneity of hepatocellular carcinoma.

Key words: hepatocellular carcinoma, copy number variation, optical genome mapping, gene expression