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.

Metalloproteinase meprin α regulates migration and invasion of human hepatocarcinoma cells and is a mediator of the oncoprotein Reptin

“…Reptin has been consistently shown overexpressed in human HCC [2, 31–33] where a high level of expression is correlated with a poor prognosis [2]. We and others have shown that Reptin is a potent mediator of oncogenesis and is considered as an attractive target in cancer [2, 3, 5–7, 34].…”

Changes in plasma circulating microvesicles in patients with HCV‐related cirrhosis after treatment with direct‐acting antivirals

“…Taleb et al elegantly performed a quantitative proteome analysis of plasma MVs in patients with HCV‐induced cirrhosis which revealed that versican core protein (VCAN) was abundant in cirrhotic patients with a further increase in HCC. VCAN is an extracellular matrix component that has been linked to various types of cancer . VCAN is also known to interact with Hyaluronan which has been proposed as a non‐invasive biomarker for liver fibrosis and cirrhosis .…”

Discovering potential serological biomarker for chronic Hepatitis B Virus-related hepatocellular carcinoma in Chinese population by MAL-associated serum glycoproteomics analysis

“…For instance, Naboulsi et al . demonstrated that versican core protein (VCAN) is a potential biomarker for early HCC diagnosis by label-free discovery analysis: selected (multiple) reaction monitoring (SRM/MRM)20. It was also reported that protein S100A9, which was dramatically up-regulated in sera from HCC patients, is a candidate HCC diagnostic biomarker21.…”