Institut Pasteur, Unité "Organisation Nucléaire et Oncogenèse", INSERM U993, Paris, France.
Sorbonne Universités, UPMC Université Paris 06, Paris, France.
Sci Rep. 2018 Aug 13;8(1):12031. doi: 10.1038/s41598-018-30229-8.
In Peru, hepatocellular carcinoma (HCC) arises in young non-cirrhotic patients. Hepatitis B virus (HBV) is suspected to be the prominent etiological agent. We thus performed a comprehensive molecular study of HBV infection in 65 Peruvian HCC patients. Only 51% were considered as persistently infected at the onset. HBV DNA was found by PCR in the tumor and/or matched non-tumor liver tissues in more than 80% of cases (n = 53/65). HBV DNA was significantly more abundant in livers of younger patients than in those of the older ones. We consistently observed low viral DNA burden (0.1-6.5 copies for 100 cells), with viral genomes in younger patients displaying higher proportion of mutations at di-pyrimidines (TpT and CpC, P = 0.006). A drastic activation of multiple DNA repair pathways in tumors of younger patients was observed. Our observations clearly challenge the current vision that associates high HBV DNA load with earlier tumor development. We concluded that in Peru, and maybe in other populations with Americas' indigenous ancestry, HBV-associated liver tumorigenesis might differ significantly from that generally observed in the rest of the world. Procedures used to screen for HCC development in subjects at risk should be adapted to the local situation.
在秘鲁，肝细胞癌 (HCC) 发生在非肝硬化的年轻患者中。乙型肝炎病毒 (HBV) 被怀疑是主要的病因。因此，我们对 65 例秘鲁 HCC 患者的 HBV 感染进行了全面的分子研究。只有 51%的患者在发病时被认为是持续感染。在超过 80%的病例（n=65/65）中，通过 PCR 在肿瘤和/或匹配的非肿瘤肝组织中发现了 HBV DNA。HBV DNA 在年轻患者的肝脏中比在老年患者的肝脏中更为丰富。我们一致观察到低病毒 DNA 负荷（100 个细胞中 0.1-6.5 拷贝），年轻患者的病毒基因组中双嘧啶（TpT 和 CpC）的突变比例更高（P=0.006）。在年轻患者的肿瘤中观察到多个 DNA 修复途径的强烈激活。我们的观察结果清楚地挑战了目前将高 HBV DNA 负荷与早期肿瘤发展联系起来的观点。我们得出结论，在秘鲁，也许在其他具有美洲土著血统的人群中，HBV 相关的肝肿瘤发生可能与世界其他地区普遍观察到的有很大不同。用于筛查高危人群 HCC 发展的程序应适应当地情况。
