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Published in: Journal of Cancer Research and Clinical Oncology 12/2020

01-12-2020 | Ultrasound | Original Article – Cancer Research

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

Authors: Amr Shaaban Hanafy, Mohamed Sorour Mohamed, Ahmed A. Alnagar

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2020

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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.
Literature
go back to reference 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):624–631CrossRefPubMed 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):624–631CrossRefPubMed
go back to reference 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):2028–2036CrossRefPubMedPubMedCentral 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):2028–2036CrossRefPubMedPubMedCentral
go back to reference Chen H, Zhang Y, Li S et al (2018) Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma. Cancer Manag Res 10:1947–1958CrossRefPubMedPubMedCentral Chen H, Zhang Y, Li S et al (2018) Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma. Cancer Manag Res 10:1947–1958CrossRefPubMedPubMedCentral
go back to reference 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):336–344CrossRefPubMed 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):336–344CrossRefPubMed
go back to reference 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. 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.
go back to reference 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):396–404CrossRef 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):396–404CrossRef
go back to reference 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):758–765CrossRef 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):758–765CrossRef
go back to reference El-Zayadi AR, Badran HM, Barakat EM et al (2005) Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol 11:5193–5198PubMedPubMedCentral El-Zayadi AR, Badran HM, Barakat EM et al (2005) Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol 11:5193–5198PubMedPubMedCentral
go back to reference 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. 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.
go back to reference 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 56:908–943CrossRef 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 56:908–943CrossRef
go back to reference 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):1139–1145CrossRefPubMedPubMedCentral 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):1139–1145CrossRefPubMedPubMedCentral
go back to reference 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):46–50CrossRef 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):46–50CrossRef
go back to reference Hood M, Skaar E (2013) Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol 10(8):525–537CrossRef Hood M, Skaar E (2013) Nutritional immunity: transition metals at the pathogen-host interface. Nat Rev Microbiol 10(8):525–537CrossRef
go back to reference Hornann C, Christensen E, Schlichting P et al (2003) Ascites fluid and plasma Calprotectin concentrations in liver disease. Scand J Gastroenterol 38:415–420CrossRef Hornann C, Christensen E, Schlichting P et al (2003) Ascites fluid and plasma Calprotectin concentrations in liver disease. Scand J Gastroenterol 38:415–420CrossRef
go back to reference 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):580–588CrossRefPubMed 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):580–588CrossRefPubMed
go back to reference 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):e69395CrossRefPubMedPubMedCentral 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):e69395CrossRefPubMedPubMedCentral
go back to reference 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):1093–1097CrossRef 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):1093–1097CrossRef
go back to reference Lehmann FS, Burri E, Beglinger C (2014) The role and utility of faecal markers in inflammatory bowel disease. Therapeutic Adv Gastroenterol 8(1):23–36CrossRef Lehmann FS, Burri E, Beglinger C (2014) The role and utility of faecal markers in inflammatory bowel disease. Therapeutic Adv Gastroenterol 8(1):23–36CrossRef
go back to reference 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):2031–2039CrossRefPubMed 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):2031–2039CrossRefPubMed
go back to reference 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 18:1894–1899CrossRefPubMed 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 18:1894–1899CrossRefPubMed
go back to reference 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):110–118CrossRefPubMed 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):110–118CrossRefPubMed
go back to reference 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):3681–3694CrossRefPubMedPubMedCentral 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):3681–3694CrossRefPubMedPubMedCentral
go back to reference 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):1251–1262CrossRefPubMed 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):1251–1262CrossRefPubMed
go back to reference 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):7895–7906CrossRef 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):7895–7906CrossRef
go back to reference 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):817–826CrossRefPubMed 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):817–826CrossRefPubMed
go back to reference 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 36:2190–2194CrossRefPubMed 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 36:2190–2194CrossRefPubMed
go back to reference Striz I, Trebichavsky I (2004) Calprotectin—a pleiotropic molecule in acute and chronic inflammation. Physiol Res Acad Sci Bohemoslovaca 53(3):245–253 Striz I, Trebichavsky I (2004) Calprotectin—a pleiotropic molecule in acute and chronic inflammation. Physiol Res Acad Sci Bohemoslovaca 53(3):245–253
go back to reference 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):75–81CrossRefPubMed 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):75–81CrossRefPubMed
go back to reference 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 50:80–88CrossRefPubMed 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 50:80–88CrossRefPubMed
go back to reference 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 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
Metadata
Title
Ascitic Calprotectin as an early predictor of hepatocellular carcinoma in patients with cirrhotic ascites
Authors
Amr Shaaban Hanafy
Mohamed Sorour Mohamed
Ahmed A. Alnagar
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 12/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-020-03363-y

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