title: Serum levels of angiogenic and anti-angiogenic factors: their prognostic relevance in locally advanced hepatocellular carcinoma.
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.
authors.affiliation: Departments of Hepatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
authors.forename: Bal Krishan
authors.initials: BK
authors.lastname: Sharma
authors.forename: Radhika
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Shweta
authors.initials: S
authors.lastname: Kapil
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Singla
authors.forename: Nitin
authors.initials: N
authors.lastname: Saini
authors.forename: Yogesh Kumar
authors.initials: YK
authors.lastname: Chawla
authors.forename: Anuradha
authors.initials: A
authors.lastname: Chakraborti
authors.forename: Ajay
authors.initials: A
authors.lastname: Duseja
authors.forename: Naveen
authors.initials: N
authors.lastname: Kalra
authors.forename: Radha Krishan
authors.initials: RK
authors.lastname: Dhiman
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000097:blood*; D020533:Angiogenesis Inhibitors / Q000097:blood*; D043168:Angiostatins / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000473:pathology*; D043169:Endostatins / Q000097:blood; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology*; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D033921:Vesicular Transport Proteins / Q000097:blood
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D043169:Endostatins; C467484:VEGFA protein, human; C555023:VPS51 protein, human; D042461:Vascular Endothelial Growth Factor A; D033921:Vesicular Transport Proteins; D043168:Angiostatins
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