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Utility of serum neuropilin-1 and angiopoietin-2 as markers of hepatocellular carcinoma
  1. Muhammad Tarek Abdel Ghafar1,
  2. Reham A Elkhouly2,
  3. Mohammed H Elnaggar3,
  4. Mohamed M Mabrouk3,
  5. Sara A Darwish4,
  6. Reham L Younis5,
  7. Rasha A Elkholy1
  1. 1Clinical Pathology, Tanta University Faculty of Medicine, Tanta, Egypt
  2. 2Tropical Medicine, Tanta University Faculty of Medicine, Tanta, Egypt
  3. 3Internal Medicine, Tanta University Faculty of Medicine, Tanta, Egypt
  4. 4Clinical Oncology and Nuclear Medicine, Tanta University Faculty of Medicine, Tanta, Egypt
  5. 5Physiology, Tanta University Faculty of Medicine, Tanta, Egypt
  1. Correspondence to Dr Muhammad Tarek Abdel Ghafar, Clinical Pathology, Tanta University Faculty of Medicine, Tanta 31511, Egypt; mohammedtarek5514{at}yahoo.com

Abstract

This study aimed to assess the diagnostic value of two serum angiogenetic markers neuropilin-1 (NRP-1) and angiopoietin-2 (ANG-2) in patients with hepatocellular carcinoma (HCC) and their relation to tumor characteristics. 149 subjects were recruited and divided into 50 patients with recently diagnosed HCC, 49 patients with cirrhosis on top of hepatitis C virus infection, and 50 healthy subjects. Serum NRP-1 and ANG-2 were estimated by ELISA. Alpha-fetoprotein (AFP) levels were measured using fluorescence immunoassay. Serum NRP-1 and ANG-2 levels were significantly higher in patients with HCC (2221.8±1056.6 pg/mL and 3018.5±841.4 pg/mL) than healthy subjects (219.3±61.8 pg/mL and 2007.7±904.8 pg/mL) and patients with cirrhosis (1108.9±526.6 pg/mL and 2179.1±599.2 pg/mL), respectively. In multivariate logistic regression analysis, NRP-1 and AFP were the only independent factors of HCC development and correlated positively with each other (r=0.781, p<0.001). Receiver operating characteristic curve analysis showed that the area under the curve (AUC) of NRP-1 was higher than that of ANG-2 in discriminating HCC from patients with cirrhosis (0.801 vs 0.748, p=0.250) and healthy subjects (0.992 vs 0.809, p<0.001). The AUC of NRP-1 was detected to be increased (0.994) when combined estimation with AFP was performed. Elevated serum NRP-1 and ANG-2 levels were detected in patients with HCC with tumor numbers >3, tumor size ≥5 cm, tumor stages B/C according to the Barcelona Clinic Liver Cancer staging system, vascular invasion, and distant metastasis. In conclusion, NRP-1 is a potential serological marker for HCC diagnosis and is better than ANG-2. It is feasible to be estimated in combination with AFP to enhance its diagnostic power. High serum NRP-1 and ANG-2 levels are associated with advanced HCC tumor characteristics.

  • carcinoma
  • hepatocellular
  • liver cirrhosis
  • angiopoietins
  • alpha-fetoproteins
  • diagnostic tests
  • routine

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • Contributors MTAG, RAE: study design, methodology, laboratory investigations, original draft writing. RAE: methodology, resources, patient selection and clinical evaluation, original draft writing. MHE, MMM: methodology, clinical evaluation. SAD: methodology, resources, patient selection and clinical evaluation. RLY: data analysis. All authors revised and approved the final manuscript version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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