| Background & Aims Hepatocellular Carcinoma (HCC) is one of the most common malignant tumor in the world. Most patients with HCC have chronic hepatitis in China. Significantly, HCC which results from chronic B hepatitis virus (HBV) has familial aggregation and genetic susceptibility, and the incidence of HCC which are correlative with the first and the second degree relative decreased progressively, furthermore, the incidence were high than population risk respectively. Therefore, it is necessary to study the susceptible mechanism of HCC related to genome-wide abnormalities. Now there were lots of studies about the susceptible mechanism of HCC at transcriptional level. Recently, the studies focus on the genome-wide study of association between CNVs and diseases at the level of DNA structural variation. CNVs are the result of duplications, deletions, insertions, inversions and complex combinations of rearrangements, and is defined as a chromosomal segment that is 1kb or larger in length, whose copy number varied in comparison to a reference genome. In a recent study CNVs have been mapped, and scientists found that genomic regions containing CNV may harbor important genes and gene regulatory elements, and may have considerable influence on disease susceptibility. Thus, we attempt to find CNVs related to carcinogenesis of HCC result from hepatitis virus infection at the level of genomic structure abnormalities, and analyze the clinico-pathological data of HCC patients after surgical resection, which may provide new path to favor the diagnosis, treatment and prognosis of HCC.Methods We screened CNVs in 25 patients with HCC by the high-resolution SNP arrays, and gained preliminary data. Then, we selected certain gene which is important in the carcinogenesis of HCC result from hepatitis virus infection, and identified the existence of CNVs by detecting the copy number of selected genes in the HCC tissue and peri-carcinomatous tissue. At the same time, we collected the clinic-pathological data of HCC patients to analyze the relationships between the prognosis of patients and the CNVs of certain genes.Results There were 1854 CNVs by screening the HCC tissue and peri-carcinomatous tissue using SNP arrays. We find 1242 CNVs with up-regulation and 612 CNVs with down-regulation, which indicates only a little of genes take part in the progression of malignant transformation. We selected Lin-28B gene which was noticeable in the present studies and five genes relevant to JAK-STAT pathway including STAT3,STAT2,STAT4,JAK1,IL-6. The results of real-time PCR showed that the copy number of STAT3 was higher in HCC tissue than in peri-carcinomatous tissue(P<0.05), and the copy numbers of STAT2,STAT4,JAK1,IL-6,Lin-28B had no significant difference between two groups (P>0.05). Then we divided patients into two groups. The copy numbers of JAK1 were higher in HCC tissue than in peri-carcinomatous tissue in group 1 and lower in group 2. Survival analysis showed that JAK1 didn't impact the prognosis of HCC patients after operation (P>0.05). Furthermore, tumor size, differentiation and the preoperative level of AFP, ALT, and AST had no significant difference between two groups (P>0.05).The analysis of STAT4 showed the same results as that of JAK1 (P >0.05). The overall 1-,3-year survival rates were 82.7%and 67.9%, respectively. Univariate analysis showed that tumor number, differentiation and preoperative level of AFP were significant factors affecting the survival(P<0.05). Multivariate analysis demonstrated that tumor number and differentiation were the independent factors affecting the survival(P<0.05).Conclusion The copy number of STAT3 was higher in HCC tissue than in peri-carcinomatous tissue, which shows that the CNVs of STAT3 play an important role in the carcinogenesis of HCC result from hepatitis virus infection. The CNVs of JAK1 and STAT4 didn't impact the prognosis and some clinico-pathological factors of HCC patients after operation. Tumor number and differentiation were the independent factors affecting the survival. The preoperative level of AFP is an important prognostic factor for the surgical management.
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