title: Serum metabolomics uncovering specific metabolite signatures of intra- and extrahepatic cholangiocarcinoma.
abstract: Cholangiocarcinoma (CC) accounts for approximately 25% of all hepatobiliary malignancies, including intra- and extrahepatic cholangiocarcinoma (ICC and ECC) and has a high mortality rate. The clinical manifestations of and liver function tests for the ICC and ECC diseases are too similar to distinguish between them. Diagnosis of ICC and ECC remains difficult because of the lack of sensitive diagnostic tests, although MRI and CT with endoscopic ultrasound provide useful diagnostic information in certain patients, but are invasive, time-consuming or expensive. Early detection is the most effective way to improve the clinical outcome of CC. Serum metabolomics provides a powerful platform for discovering novel biomarkers to improve early diagnosis. This study was performed using a metabolomics method which was used to select serum metabolites to be used for the early diagnosis of CC and to distinguish ICC from ECC. We comprehensively analyzed the serum metabolites in a total of 261 blood samples from CC patients and normal individuals. We found that 75 metabolites were filtered and identified from the serum metabolome, and the levels of 21-deoxycortisol and bilirubin significantly increased while the levels of lysoPC(14:0) and lysoPC(15:0) were significantly reduced in the CC group compared with the control groups. We measured the 4 metabolites of interest in an independent sample comprising 225 cases and 101 controls. Noticeably, external validation of the serum specimens further showed that the biomarker combination could differentiate ECC and ICC patients with high accuracy. This provides a new foundation for serum metabolomics to provide potential biomarkers for the early detection of CC.
authors.affiliation: ICU Center, First Affiliated Hospital, School of Pharmacy, Heilongjiang University of Chinese Medicine, Heping Road 24, Xiangfang District, Harbin 150040, China. qunliang1970@126.com.
authors.forename: Qun
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Simon Fraser University (SFU), Burnaby, British Columbia, Canada.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: ICU Center, First Affiliated Hospital, School of Pharmacy, Heilongjiang University of Chinese Medicine, Heping Road 24, Xiangfang District, Harbin 150040, China. qunliang1970@126.com.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhang
authors.affiliation: ICU Center, First Affiliated Hospital, School of Pharmacy, Heilongjiang University of Chinese Medicine, Heping Road 24, Xiangfang District, Harbin 150040, China. qunliang1970@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: ICU Center, First Affiliated Hospital, School of Pharmacy, Heilongjiang University of Chinese Medicine, Heping Road 24, Xiangfang District, Harbin 150040, China. qunliang1970@126.com.
authors.forename: Haitao
authors.initials: H
authors.lastname: Xing
authors.affiliation: ICU Center, First Affiliated Hospital, School of Pharmacy, Heilongjiang University of Chinese Medicine, Heping Road 24, Xiangfang District, Harbin 150040, China. qunliang1970@126.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D001650:Bile Duct Neoplasms / Q000097:blood* / Q000175:diagnosis; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000097:blood* / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: D014408:Biomarkers, Tumor