title: Role of 5-hydroxymethylcytosine level in diagnosis and prognosis prediction of intrahepatic cholangiocarcinoma.
abstract: The loss of 5-hydroxymethylcytosine (5-hmC) has been identified as an epigenetic hallmark in several malignancies. However, its role in intrahepatic cholangiocarcinoma (ICC) is still unknown. Our study aims to investigate the level of 5-hmC in diagnosis and prognosis prediction of ICC. The 5-hmC levels were detected using dot blot, tissue microarray technique and immunohistochemical method, and the correlation between 5-hmC level and ICC clinicopathological parameters was analysed. Compared with matched liver tissues, most of ICC tissues presented with the loss of 5-hmC. Furthermore, the subgroups of cirrhotic and poor differentiation tissues showed the lowest level of 5-hmC. We found that 5-hmC level in non-elevated ICC patients was significantly related to lymph node metastasis and TNM stage and not related to vessel invasion, sex, age, HBV, cirrhosis or degree of differentiation. ICC patients with high TNM stage (stages III and IV) and lymph node metastases had significantly lower 5-hmC level than those with low TNM stage (stages I and II) and no lymph node metastases. Further analysis showed that low 5-hmC level is significantly correlated with worse overall survival (OS) and disease-free survival (DFS). Importantly, multivariate analysis indicated that 5-hmC level, tumour diameter, lymphatic metastasis and tumour differentiation could be used as independent prognostic factors for ICC. The loss of 5-hmC is implicated in the progression of ICC. Our results can contribute to the diagnostic ability and postoperative surveillance of ICC patients.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.
authors.forename: Zhao-Ru
authors.initials: ZR
authors.lastname: Dong
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Cai
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Zhang
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Shi
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Gao
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Ai-Wu
authors.initials: AW
authors.lastname: Ke
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000293:Adolescent; D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine