title: Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma.
abstract: Hepatocellular carcinoma (HCC) is one of the most aggressive tumors, and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing an accurate and early tumor diagnosis. To identify potential markers for such applications, we analyzed a patient cohort consisting of 50 patients (50 HCC and 50 adjacent nontumorous tissue samples as controls) using two independent proteomics approaches. We performed label-free discovery analysis on 19 HCC and corresponding tissue samples. The data were analyzed considering events known to take place in early events of HCC development, such as abnormal regulation of Wnt/b-catenin and activation of receptor tyrosine kinases (RTKs). 31 proteins were selected for verification experiments. For this analysis, the second set of the patient cohort (31 HCC and corresponding tissue samples) was analyzed using selected (multiple) reaction monitoring (SRM/MRM). We present the overexpression of ATP-dependent RNA helicase (DDX39), Fibulin-5 (FBLN5), myristoylated alanine-rich C-kinase substrate (MARCKS), and Serpin H1 (SERPINH1) in HCC for the first time. We demonstrate Versican core protein (VCAN) to be significantly associated with well differentiated and low-stage HCC. We revealed for the first time the evidence of VCAN as a potential biomarker for early-HCC diagnosis.
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Wael
authors.initials: W
authors.lastname: Naboulsi
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Dominik A
authors.initials: DA
authors.lastname: Megger
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Bracht
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kohl
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Turewicz
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Don Marvin
authors.initials: DM
authors.lastname: Voss
authors.forename: Jörg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Andreas-Claudius
authors.initials: AC
authors.lastname: Hoffmann
authors.forename: Frank
authors.initials: F
authors.lastname: Weber
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.affiliation: Medizinisches Proteom-Center, Ruhr-Universität Bochum , 44801 Bochum, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D040901:Proteomics; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor
keywords: Versican; early diagnosis biomarker; hepatocellular carcinoma; label-free proteomics; multiple reaction monitoring; selected reaction monitoring; targeted proteomics