Abstract

The detection and diagnosis of hepatocellular carcinoma (HCC) at an early stage may significantly affect the prognosis of HCC patients. Thus, it is necessary to always identify novel putative markers for improving diagnosis. Hepatocarcinogenesis correlates with pathological hepatic angiogenesis. However, each tumor-induced angio-genetic process is influenced by the microenvironment through several pro- and anti-angiogenic factors released from tumor cells, tumor-associated inflammatory cells and/or from the extracellular matrix, and modulated by various signal pathways. In this study, we evaluated the profiling of angiogenic factors using Bio-Plex Pro™ Human Cancer Biomarker Panel1, a 16-plex magnetic bead-based assay, in sera of patients with chronic hepatitisC (CHC) virus, liver cirrhosis (LC) and HCC. Our results demonstrated: i)high levels of hepatocyte growth factor (HGF) and prolactin only in LC and HCC patients, ii)high levels of soluble human epidermal growth factor receptor‑2 (sHER-2/neu; ErbB-2), sIL-6Ra, leptin (LEP) and platelet endothelial cell adhesion molecule‑1 (PECAM-1) in CHC, LC and HCC patients and iii)that sIL-6R correlated with the fibrosis stage in CHC patients, with Child‑Pugh score in those patients with LC and with tumor size in those patients with HCC, confirming that this protein may be used as a predictor of liver damage and of inflammatory process leading to fibrosis, cirrhosis, and subsequently to cancer. Moreover, an interactomic study conducted using the Ingenuity Pathway Analysis (IPA) software proved the existence of a correlation between 5significant proteins [ErbB-2, sIL-6Ra, prolactin (PRL), HGF and LEP] which are involved in the same metabolic pathways.

Highlights

  • Hepatocellular carcinoma (HCC) is the fifth most common and the third most lethal cancer worldwide, accounting for 550,000 deaths annually

  • We discovered prognostic biomarkers for the chronic hepatitis C (CHC) virus infection process leading to liver cirrhosis (LC) and HCC by composite profiling of serum angiogenic factors using the Bio-Plex ProTM Human Cancer Biomarker Panel 1, a 16-plex unique blend of magnetic bead-based assays

  • The varying levels of the proteins present in the serum of CHC, LC and HCC patients compared to the healthy controls are presented in Table II

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common and the third most lethal cancer worldwide, accounting for 550,000 deaths annually. We discovered prognostic biomarkers for the chronic hepatitis C (CHC) virus infection process leading to liver cirrhosis (LC) and HCC by composite profiling of serum angiogenic factors using the Bio-Plex ProTM Human Cancer Biomarker Panel 1, a 16-plex unique blend of magnetic bead-based assays. The advantages of this multiplex approach include specimen conservation, limited sample handling, increased throughput and reduced labor costs

Patients and methods
Results and Discussion
El-Serag HB and Rudolph KL
Behne T and Copur MS
Semela D and Dufour JF
17. Montero-Julian FA
21. Reeves HL and Friedman SL
24. Newman PJ and Newman DK
30. Sahu A

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