S-Space College of Medicine/School of Medicine (의과대학/대학원) Pathology (병리학전공) Journal Papers (저널논문_병리학전공)
Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma
- Jeong, Seorin; Lee, Kyoungbun; Wen, Xianyu; Kim, Younghoon; Cho, Nam-Yun; Jang, Ja-June; Kang, Gyeong Hoon
- Issue Date
- BioMed Central
- BMC Cancer, 17(1):588
- ECC: Extrahepatic cholangiocarcinoma; ICC: Intrahepatic cholangiocarcinoma;
IG: Intraductal growth; LINE-1: Long interspersed element-1; MF: Mass-forming;
PI: Periductal infiltrative; TNM: Tumor, node, and metastasis
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.