早发肝癌（发病〈40岁）恶性程度更高、起病更隐匿、临床更难发现。囿于样本和技术手段限制, 目前针对早发肝癌研究较少。我们前期利用病毒捕获测序发现，8q24MYC/PVT1增强子区存在早发肝癌高频整合位点HBx-SINE，整合后上调MYC/PVT1表达。且HBx-SINE在癌旁和外周血单个核细胞（PMBC）中均能检出，提示其可能为生殖系整合。由此推测：HBV感染生殖细胞后发生整合，整合片段如HBx-SINE通过生殖细胞传递给子代，使子代出生即携带“第一次打击”，因而发病年龄更早。本项目将进一步扩大临床样本验证HBx-SINE在早发肝癌中的作用；利用细胞和动物实验阐明HBx-SINE通过激活增强子上调MYC、PVT1、进而促进肝癌早发的分子机制；利用FISH等获得HBV整合子代传递的直接证据，最终阐明HBV整合通过垂直传递促进肝癌早发的作用机制，为早发肝癌诊断与个体化治疗提供分子靶点和理论基础

Compared with late-onset hepatocellular carcinoma（HCC）, Early-onset HCC (< 40 years old) is more malignant, more insidious and more difficult to detect. Limited by clinical samples and research methods, there are few studies focused on early-onset HCC. Our pilot study identified a high frequency HBV integration site, HBx-SINE， in early-onset HCC by using virus capture sequencing methods. We further detected HBx-SINE in normal tissues adjacent to tumor and peripheral blood mononuclear cells (PMBC), suggests the integration site may be not a somatic integration, but a germline integration. Based on these observations, we speculate that after HBV infection germ cells, HBV integrated in these cells, consequently, the HBV integration sites passed to the offspring embryo cells, so that the child was born carrying a "first hit", thus with a earlier onset HCC. The project will further Confirmed the hypothesis by: expanding clinical samples to validate HBx-SINE detection earlier-onset HCC, use of cell and animal experiments to illustrate HBx-SINE up-regulating MYC and PVT1 expression and in turn, promote the development of early-onset HCC. Finally, we use of abandoned germ cell or embryo to confirm HBV vertical transmission characteristics of HBV integration, thus finally clarify vertical transmission of HBV integration and the role and mechanisms of HBV integration in the early-onset HCC. Our work will provide new target for early-onset HCC detection and treatment. We also provide a new theoretical basis for HBV integration in early-onset HCC.