title: Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery.
abstract: Hepatocellular carcinoma (HCC) is one of the pestilent malignancies leading to cancer-related death. Discovering effective biomarkers for HCC diagnosis is an urgent demand. To identify potential metabolite biomarkers, we developed a urinary pseudotargeted method based on liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (LC-QTRAP MS). Compared with nontargeted method, the pseudotargeted method can achieve better data quality, which benefits differential metabolites discovery. The established method was applied to cirrhosis (CIR) and HCC investigation. It was found that urinary nucleosides, bile acids, citric acid, and several amino acids were significantly changed in liver disease groups compared with the controls, featuring the dysregulation of purine metabolism, energy metabolism, and amino metabolism in liver diseases. Furthermore, some metabolites such as cyclic adenosine monophosphate, glutamine, and short- and medium-chain acylcarnitines were the differential metabolites of HCC and CIR. On the basis of binary logistic regression, butyrylcarnitine (carnitine C4:0) and hydantoin-5-propionic acid were defined as combinational markers to distinguish HCC from CIR. The area under curve was 0.786 and 0.773 for discovery stage and validation stage samples, respectively. These data show that the established pseudotargeted method is a complementary one of targeted and nontargeted methods for metabolomics study.
authors.affiliation: Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , 457 Zhongshan Road, Dalian 116023, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Shao
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.forename: Ruiyin
authors.initials: R
authors.lastname: Zheng
authors.forename: Xinjie
authors.initials: X
authors.lastname: Zhao
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Yin
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Binghua
authors.initials: B
authors.lastname: Jiao
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000652:urine*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000652:urine; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000652:urine; D008113:Liver Neoplasms / Q000378:metabolism* / Q000652:urine; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor
keywords: LC−MS; cirrhosis; hepatocellular carcinoma; metabolomics; pseudotargeted method; urine