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Ascitic Calprotectin as an early predictor of hepatocellular carcinoma in patients with cirrhotic ascites

  • Original Article – Cancer Research
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A Correction to this article was published on 18 November 2021

This article has been updated

Abstract

Background

Calprotectin is a heterodimer formed by S100A8 and S100A9 proteins which are enhanced during hepatic carcinogenesis and the increased expression of both proteins promotes malignant progression of hepatocellular carcinoma. The potential correlation between ascitic Calprotectin and HCC was not studied.

Methods

100 patients were stratified into a case group which enrolled 50 patients with cirrhotic ascites and documented HCC and a control group consisted of 50 patients with cirrhotic ascites without HCC. They were evaluated by liver function tests, abdominal ultrasound and routine ascitic fluid examination including ascetic Calprotectin and results were validated in another group (n = 100).

Results

Calprotectin level was significantly higher in the HCC group with insignificant difference regarding total cell count, PNLs, ascitic albumin, LDH, CEA and SAAG. It correlated with serum creatinine (r = 0.245, p = 0.014) and number of focal hepatic lesions (r = 0.309, p = 0.002). In the validation group, 28 patients had elevated ascitic Calprotectin of which 21 patients had developed HCC (75%) after a mean period of 3.8 ± 1.54 months. A cut of value 126 ng/ml was accurate to predict HCC in liver cirrhosis with ascites with a sensitivity of 93.3% specificity 94%, AUC 0.950, Youden’s J value = 0.873, p = 0.0001.

Conclusion

Ascitic Calprotectin may offer an easy, affordable marker that can predict the early occurrence of HCC.

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Abbreviations

USG:

Abdominal ultrasonography

CEA:

Carcinoembryonic antigen

HCC:

Hepatocellular carcinoma

ROC:

Receiver operator characteristics

PNLs:

Polymorphonuclear neutrophils

SAAG:

Serum-ascites albumin gradient

SBP:

Spontaneous bacterial peritonitis

References

  • Ahmed Abdel-Razik A, Mousa N, Elhammady D et al (2016) Ascitic fluid calprotectin and serum procalcitonin as accurate diagnostic markers for spontaneous bacterial peritonitis. Gut Liver 10(4):624–631

    Article  PubMed  Google Scholar 

  • Burri E, Schulte F, Muser J et al (2013) Measurement of Calprotectin in ascitic fluid to identify elevated polymorphonuclear cell count. World J Gastroenterol 19(13):2028–2036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Zhang Y, Li S et al (2018) Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma. Cancer Manag Res 10:1947–1958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clark HL, Jhingran A, Sun Y et al (2016) Zinc and manganese chelation by neutrophil S100A8/A9 (Calprotectin) limits extracellular Aspergillus fumigates Hyphal growth and corneal infection. J Immunol 196(1):336–344

    Article  CAS  PubMed  Google Scholar 

  • Dai M, Chen X, Liu X, et al (2015). Diagnostic value of the combination of Golgi protein 73 and alpha-fetoprotein in hepatocellular carcinoma: a meta-analysis Plos One 10(10), Article e0140067.

  • De Ponti A, Wiechert L, Schneller D et al (2015) A pro-tumorigenic function of S100A8/A9 in carcinogen-induced hepatocellular carcinoma. Cancer Lett 28 369(2):396–404

    Article  Google Scholar 

  • Duarte-Salles T, Misra S, Stepien M et al (2016) Circulating osteopontin and prediction of hepatocellular carcinoma development in a large European population. Canc Prev Res 9(9):758–765

    Article  CAS  Google Scholar 

  • El-Zayadi AR, Badran HM, Barakat EM et al (2005) Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol 11:5193–5198

    PubMed  PubMed Central  Google Scholar 

  • Enomoto H, Inoue S, Matsuhisa A, et al (2014). Diagnosis of spontaneous bacterial peritonitis and an in situ hybridization approach to detect an "unidentified" pathogen. Int J Hepatol:634617.

  • European Association for the Study of The Liver; European Organization For Research And Treatment Of Cancer (2012) EASL-EORTC Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943

    Article  Google Scholar 

  • Fernandes SR, Santos P, Fatela N et al (2016) Ascitic Calprotectin is a novel and accurate marker for spontaneous bacterial peritonitis. J Clin Lab Anal 30(6):1139–1145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta S, Bent S, Kohlwes J (2013) Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C, a systematic review and critical analysis. Ann Intern Med 139(1):46–50

    Article  Google Scholar 

  • Hood M, Skaar E (2013) Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol 10(8):525–537

    Article  Google Scholar 

  • Hornann C, Christensen E, Schlichting P et al (2003) Ascites fluid and plasma Calprotectin concentrations in liver disease. Scand J Gastroenterol 38:415–420

    Article  Google Scholar 

  • Jia X, Liu J, Gao Y et al (2014) Diagnosis accuracy of serum glypican-3 in patients with hepatocellular carcinoma: a systematic review with meta-analysis. Arch Med Res 45(7):580–588

    Article  CAS  PubMed  Google Scholar 

  • Khammanivong A, Wang C, Sorenson BS et al (2013) S100A8/A9 (Calprotectin) negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma. PLoS ONE 8(7):e69395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kong JP, Ding F, Zhou CN et al (2004) Loss of myeloid-related proteins 8 and myeloid-related proteins 14 expression in human esophageal squamous cell carcinoma correlates with poor differentiation. World J Gastroenterol 15 10(8):1093–1097

    Article  CAS  Google Scholar 

  • Lehmann FS, Burri E, Beglinger C (2014) The role and utility of faecal markers in inflammatory bowel disease. Therapeutic Adv Gastroenterol 8(1):23–36

    Article  Google Scholar 

  • Lutz P, Pfarr K, Nischalke HD et al (2015) The ratio of Calprotectin to total protein as a diagnostic and prognostic marker for spontaneous bacterial peritonitis in patients with liver cirrhosis and ascites. Clin Chem Lab Med 53(12):2031–2039

    Article  CAS  PubMed  Google Scholar 

  • Mao R, Xiao YL, Gao X et al (2012) Fecal Calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflamm Bowel Dis 18:1894–1899

    Article  PubMed  Google Scholar 

  • Marrero JA, Feng Z, Wang Y et al (2009) Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology 137(1):110–118

    Article  CAS  PubMed  Google Scholar 

  • Mumolo MG, Bertani L, Ceccarelli L et al (2018) From bench to bedside: Fecal Calprotectin in inflammatory bowel diseases clinical setting. World J Gastroenterol 24(33):3681–3694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Németh J, Stein I, Haag D et al (2009) S100A8 and S100A9 are novel nuclear factor kappa B target genes during malignant progression of murine and human liver carcinogenesis. Hepatology 50(4):1251–1262

    Article  PubMed  Google Scholar 

  • Pang Q, Qu K, Bi JB et al (2015) Thrombocytopenia for prediction of hepatocellular carcinoma recurrence: Systematic review and meta-analysis. World J Gastroenterol 7 21(25):7895–7906

    Article  Google Scholar 

  • Shen Q, Fan J, Yang XR et al (2012) Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol 13(8):817–826

    Article  CAS  PubMed  Google Scholar 

  • Soyfoo MS, Roth J, Vogl T et al (2009) Phagocyte-specific S100A8/A9 protein levels during disease exacerbations and infections in systemic lupus erythematosus. J Rheumatol 36:2190–2194

    Article  CAS  PubMed  Google Scholar 

  • Striz I, Trebichavsky I (2004) Calprotectin—a pleiotropic molecule in acute and chronic inflammation. Physiol Res Acad Sci Bohemoslovaca 53(3):245–253

    CAS  Google Scholar 

  • Yong HY, Moon A (2007) Roles of calcium-binding proteins S100A8 and S100A9 in invasive phenotype of human gastric cancer cells. Arch Pharm Res 30(1):75–81

    Article  CAS  PubMed  Google Scholar 

  • Yuen MF, Tanaka Y, Fong DY et al (2009) Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol 50:80–88

    Article  PubMed  Google Scholar 

  • Ziada DH, El Sadany S, Soliman H et al (2016) Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in mid delta, Egypt: a single center study egypt. Natl Canc Inst 28(4):257–262

    Google Scholar 

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Funding

Self-funded.

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Authors and Affiliations

  1. Internal Medicine Department, Hepatogastroenterology Division, Zagazig University, Zagazig, 40 Mostafa Fouad street, 44519, Egypt

    Amr Shaaban Hanafy & Mohamed Sorour Mohamed

  2. Medical Oncology, Zagazig University, Zagazig, Egypt

    Ahmed A. Alnagar

Authors
  1. Amr Shaaban Hanafy
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  2. Mohamed Sorour Mohamed
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  3. Ahmed A. Alnagar
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Contributions

ASH: research methodology. AH, AAA and MSM: clinical analysis, data collection. ASH: ultrasound evaluation and statistical analysis.

Corresponding author

Correspondence to Amr Shaaban Hanafy.

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There are no conflicts of interest.

Ethical approval

The study was approved by Zagazig University institutional research committee. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee.

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Amr Shaaban Hanafy.

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The original online version of this article was revised due to correction in figures 3 and 4.

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Hanafy, A.S., Mohamed, M.S. & Alnagar, A.A. Ascitic Calprotectin as an early predictor of hepatocellular carcinoma in patients with cirrhotic ascites. J Cancer Res Clin Oncol 146, 3207–3214 (2020). https://doi.org/10.1007/s00432-020-03363-y

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  • DOI: https://doi.org/10.1007/s00432-020-03363-y

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