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

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.