title: Identifying serological biomarkers of hepatocellular carcinoma using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy.
abstract: Lack of sensitive and specific biomarkers is a major reason for the high rate of hepatocellular carcinoma (HCC) related mortality. The aim of this study was to use surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS) technology to identify potential protein patterns specific for HCC. Eighty-one patients with hepatitis B-related HCC and 80 healthy controls were randomly divided into a training set (48 HCC, 47 controls) and a testing set (33 HCC, 33 controls). Serum proteomic profiles were measured using SELDI-TOF-MS. A classification tree was established by Biomarker Pattern Software. Candidate biomarkers were separated by HPLC and identified by MALDI-MS/MS and database searching. Forty-eight HCC cases, 54 liver cirrhosis cases and 42 healthy people were clinically validated using candidate biomarkers by SELDI-Immunoassay. Two up-regulated protein peaks were automatically chosen as a classification tree in the training set. These biomarkers were identified as thrombin light chain and growth related oncogene-alpha (GRO-alpha). The sensitivity and specificity of this classification tree were 89.6%. The multivariate model using the two biomarkers and AFP resulted in a sensitivity of 91.7% and specificity of 92.7%, which was significantly better than that of alpha-fetoprotein alone. We conclude that thrombin light chain and GRO-alpha are potential biomarkers of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, PR China.
authors.forename: Fei-Xiang
authors.initials: FX
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Shang
authors.initials: S
authors.lastname: Huang
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Yuan
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Liu
authors.forename: Ke-Chen
authors.initials: KC
authors.lastname: Ban
authors.forename: Yin-Nong
authors.initials: YN
authors.lastname: Zhao
mesh_terms: D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D054360:Chemokine CXCL1 / Q000378:metabolism; D006509:Hepatitis B / Q000097:blood / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000209:etiology; D008297:Male; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D020543:Proteome / Q000378:metabolism*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013917:Thrombin / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D020543:Proteome; D000509:alpha-Fetoproteins; D013917:Thrombin