Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Jeong|Seorin|S|', 'Lee|Kyoungbun|K|', 'Wen|Xianyu|X|', 'Kim|Younghoon|Y|', 'Cho|Nam-Yun|NY|', 'Jang|Ja-June|JJ|', 'Kang|Gyeong Hoon|GH|http://orcid.org/0000-0003-2380-6675']
D001650:Bile Duct Neoplasms D014408:Biomarkers, Tumor D018281:Cholangiocarcinoma D018899:CpG Islands D019175:DNA Methylation D005260:Female D006801:Humans D020084:Long Interspersed Nucleotide Elements D008297:Male D009361:Neoplasm Invasiveness D009367:Neoplasm Staging D011379:Prognosis D017422:Sequence Analysis, DNA D016019:Survival Analysis
Line-1 Cholangiocarcinoma Methylation Pyrosequencing Prognosis