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

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Abstract

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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Acknowledgments

This work was financially supported by Indian Council of Medical Research (ICMR), New Delhi (Grant No. 5/13/17/2004-NCD-III).

Disclosures

All the authors disclose that they have no financial, professional or personal conflict of interest.

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Authors and Affiliations

  1. Departments of Hepatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India

    Bal Krishan Sharma, Shweta Kapil, Bhupesh Singla, Nitin Saini, Yogesh Kumar Chawla, Ajay Duseja & Radha Krishan Dhiman

  2. Department of Cytology and Gynecological Pathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India

    Radhika Srinivasan

  3. Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India

    Anuradha Chakraborti

  4. Department of Radiodiagnosis, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India

    Naveen Kalra

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  1. Bal Krishan Sharma
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Correspondence to Yogesh Kumar Chawla.

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Sharma, B.K., Srinivasan, R., Kapil, S. et al. Serum levels of angiogenic and anti-angiogenic factors: their prognostic relevance in locally advanced hepatocellular carcinoma. Mol Cell Biochem 383, 103–112 (2013). https://doi.org/10.1007/s11010-013-1759-7

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