Serum levels of angiogenic and anti-angiogenic factors: their prognostic relevance in locally advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prototype tumor wherein angiogenesis plays a vital role in its progression. The role of VEGF, a major angiogenic factor in HCC is known; however, the role of anti-angiogenic factors simultaneously with the angiogenic factors has not been studied before. Hence, in...

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Veröffentlicht in:Molecular and cellular biochemistry 2013-11, Vol.383 (1-2), p.103-112
Hauptverfasser: Sharma, Bal Krishan, Srinivasan, Radhika, Kapil, Shweta, Singla, Bhupesh, Saini, Nitin, Chawla, Yogesh Kumar, Chakraborti, Anuradha, Duseja, Ajay, Kalra, Naveen, Dhiman, Radha Krishan
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container_end_page 112
container_issue 1-2
container_start_page 103
container_title Molecular and cellular biochemistry
container_volume 383
creator Sharma, Bal Krishan
Srinivasan, Radhika
Kapil, Shweta
Singla, Bhupesh
Saini, Nitin
Chawla, Yogesh Kumar
Chakraborti, Anuradha
Duseja, Ajay
Kalra, Naveen
Dhiman, Radha Krishan
description Hepatocellular carcinoma (HCC) is a prototype tumor wherein angiogenesis plays a vital role in its progression. The role of VEGF, a major angiogenic factor in HCC is known; however, the role of anti-angiogenic factors simultaneously with the angiogenic factors has not been studied before. Hence, in this study, the serum levels of major angiogenic [Vascular Endothelial Growth Factor (VEGF), angiopoietin-2 (Ang-2)] and anti-angiogenic (endostatin, angiostatin) factors were analyzed and correlated with clinico-radiological features and with outcome. A total of 150 patients (50 HCC, 50 cirrhosis and 50 chronic hepatitis) and 50 healthy controls were enrolled in this study. Serum levels of VEGF, Ang-2, endostatin, and angiostatin were estimated by enzyme-linked immunosorbent assay. HCC shows significantly elevated serum levels of angiogenic factors VEGF and Ang-2 and of anti-angiogenic factors endostatin and angiostatin. ROC curve analysis for serum VEGF yielded an optimal cut-off value of 225.14 pg/ml, with a sensitivity of 78 % and specificity of 84.7 % for a diagnosis of HCC and its distinction from other group. Using this value, the univariate and multivariate analysis revealed significantly poor outcome in patients with higher levels of serum VEGF ( p  = 0.009). Combinatorial analysis revealed that patients with higher levels of both angiogenic and anti-angiogenic factors showed poor outcome. Serum VEGF correlates with poor survival of HCC patients and, therefore, serves as a non-invasive biomarker of poor prognosis. Moreover, elevated levels of anti-angiogenic factors occur endogenously in HCC patients.
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The role of VEGF, a major angiogenic factor in HCC is known; however, the role of anti-angiogenic factors simultaneously with the angiogenic factors has not been studied before. Hence, in this study, the serum levels of major angiogenic [Vascular Endothelial Growth Factor (VEGF), angiopoietin-2 (Ang-2)] and anti-angiogenic (endostatin, angiostatin) factors were analyzed and correlated with clinico-radiological features and with outcome. A total of 150 patients (50 HCC, 50 cirrhosis and 50 chronic hepatitis) and 50 healthy controls were enrolled in this study. Serum levels of VEGF, Ang-2, endostatin, and angiostatin were estimated by enzyme-linked immunosorbent assay. HCC shows significantly elevated serum levels of angiogenic factors VEGF and Ang-2 and of anti-angiogenic factors endostatin and angiostatin. 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subjects Angiogenesis
Angiogenesis Inducing Agents - blood
Angiogenesis Inhibitors - blood
Angiostatins - blood
Antimitotic agents
Antineoplastic agents
Biochemistry
Biomarkers
Biomedical and Life Sciences
Carcinoma, Hepatocellular - blood
Carcinoma, Hepatocellular - pathology
Cardiology
Endostatins - blood
Hepatitis
Hepatoma
Humans
Kaplan-Meier Estimate
Life Sciences
Liver cancer
Liver cirrhosis
Liver Neoplasms - blood
Liver Neoplasms - pathology
Medical Biochemistry
Multivariate Analysis
Neoplasm Staging
Oncology
Prognosis
Proportional Hazards Models
ROC Curve
Tumors
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - blood
Vesicular Transport Proteins - blood
title Serum levels of angiogenic and anti-angiogenic factors: their prognostic relevance in locally advanced hepatocellular carcinoma
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