title: Serum and urine metabolite profiling reveals potential biomarkers of human hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a common malignancy in the world with high morbidity and mortality rate. Identification of novel biomarkers in HCC remains impeded primarily because of the heterogeneity of the disease in clinical presentations as well as the pathophysiological variations derived from underlying conditions such as cirrhosis and steatohepatitis. The aim of this study is to search for potential metabolite biomarkers of human HCC using serum and urine metabolomics approach. Sera and urine samples were collected from patients with HCC (n = 82), benign liver tumor patients (n = 24), and healthy controls (n = 71). Metabolite profiling was performed by gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography-quadrupole time of flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. Forty three serum metabolites and 31 urinary metabolites were identified in HCC patients involving several key metabolic pathways such as bile acids, free fatty acids, glycolysis, urea cycle, and methionine metabolism. Differentially expressed metabolites in HCC subjects, such as bile acids, histidine, and inosine are of great statistical significance and high fold changes, which warrant further validation as potential biomarkers for HCC. However, alterations of several bile acids seem to be affected by the condition of liver cirrhosis and hepatitis. Quantitative measurement and comparison of seven bile acids among benign liver tumor patients with liver cirrhosis and hepatitis, HCC patients with liver cirrhosis and hepatitis, HCC patients without liver cirrhosis and hepatitis, and healthy controls revealed that the abnormal levels of glycochenodeoxycholic acid, glycocholic acid, taurocholic acid, and chenodeoxycholic acid are associated with liver cirrhosis and hepatitis. HCC patients with alpha fetoprotein values lower than 20 ng/ml was successfully differentiated from healthy controls with an accuracy of 100% using a panel of metabolite markers. Our work shows that metabolomic profiling approach is a promising screening tool for the diagnosis and stratification of HCC patients.
authors.affiliation: Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Tianlu
authors.initials: T
authors.lastname: Chen
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Zheng
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Lisa X
authors.initials: LX
authors.lastname: Xu
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood / Q000652:urine; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000652:urine; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D009367:Neoplasm Staging; D025341:Principal Component Analysis; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000378:metabolism / Q000652:urine
chemical_list: D001647:Bile Acids and Salts; D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins