Jeong Seorin, Lee Kyoungbun, Wen Xianyu, Kim Younghoon, Cho Nam-Yun, Jang Ja-June, Kang Gyeong Hoon
Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, South Korea.
BMC Cancer. 2017 Aug 29;17(1):588. doi: 10.1186/s12885-017-3595-8.
DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5' untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas.
A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival.
Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter.
Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study.
癌细胞中发生的DNA甲基化变化具有启动子CpG岛高甲基化和弥漫性基因组低甲基化的特征。长散在核元件1（LINE-1）以散在的方式重复，每个基因组估计有500,000个拷贝。LINE-1的5'非翻译区的CpG位点在正常细胞中高度甲基化，并在癌变过程中发生去甲基化。然而，关于LINE-1低甲基化及其在肝内胆管癌中的预后意义的信息很少。
使用亚硫酸氢盐焦磷酸测序分析了172例肝内胆管癌在LINE-1的四个CpG位点的甲基化水平。我们研究了肿瘤LINE-1甲基化水平与临床病理特征（包括生存率）之间的关系。
肿瘤分化、淋巴侵犯和T分期与LINE-1在四个CpG位点的平均低甲基化水平相关；在高分化、淋巴栓子和较高T分期中，LINE-1甲基化水平往往较低。LINE-1低甲基化与肝内胆管癌患者较低的癌症特异性生存率显著相关，并被发现是一个独立的预后参数。
我们的研究结果表明，肿瘤LINE-1低甲基化可能是肝内胆管癌患者预后不良的分子生物标志物。我们的研究结果需要在进一步的研究中得到验证。
