S-Space College of Medicine/School of Medicine (의과대학/대학원) Program in Cancer Biology (협동과정-종양생물학전공) Theses (Master's Degree_협동과정-종양생물학전공)
Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma
- 의과대학 협동과정 종양생물학전공
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 종양생물학전공, 2017. 2. 강경훈.
- DNA methylation changes occurring in cancer cells are characterized by both promoter CpG island hypermethylation and diffuse genomic hypomethylation. LINE-1 is half-million times repeated in the human genome in an interspersed manner and CpG sites located in 5 untranslated region of LINE-1 are heavily methylated in normal cells and undergo demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas. We analyzed 172 cases of intrahepatic cholangiocarcinomas for their methylation status at four CpG sites of LINE-1 using pyrosequencing and correlated LINE-1 methylation level with clinicopathological features. 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. Lower methylation status of LINE-1 was significantly associated with lower overall survival in patients with intrahepatic cholangiocarcinoma and 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. A further study is required to validate our findings.