4.7 Article

Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 15, Issue 1, Pages 38-47

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.5b00420

Keywords

hepatocellular carcinoma; label-free proteomics; early diagnosis biomarker; targeted proteomics; multiple reaction monitoring; selected reaction monitoring; Versican

Funding

  1. PROFILE project - European Union (European Regional Development Fund - Investing in your future)
  2. German federal state North Rhine-Westphalia (NRW) [z0911bt004e]
  3. P.U.R.E. (Protein research Unit Ruhr within Europe), a project of North Rhine-Westphalia, a federal state of Germany

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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-Idnase 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.

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