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Tumor Biology

, Volume 37, Issue 2, pp 2539–2546 | Cite as

A suggested guiding panel of seromarkers for efficient discrimination between primary and secondary human hepatocarcinoma

  • Nabil Mohie Abdel-Hamid
  • M. M. Abouzied
  • M. H. Nazmy
  • M. A. Fawzy
  • A. S. Gerges
Original Article

Abstract

Although alpha-fetoprotein (AFP) is a golden diagnostic marker for hepatocellular carcinoma (HCC), its value is debatable. Differentiation between primary and secondary hepatocarcinomas (HC) relying on AFP is confusing, does not exceed 20 % in the later. To find alternative markers other than AFP to differentiate between primary and secondary HC from colorectal carcinoma (CRC) and breast (BC) and lung cancers (LC), 60 individuals were recruited: group 1, healthy volunteers; group 2, with primary; and group 3, with secondary HC. Carcinoembryonic antigen (CEA), total glycosaminoglycans (TGAGs), total sialic acid (TSA), free glucosamine (FGA), leucine aminopeptidase (LAP), 5′-nucleotidase (5′-NU) activities, and AFP were estimated in sera, in addition to liver histology. CEA, TGAGs, TSA, and FGA were elevated in secondary HC among CRC primary cancers, while LAP, 5′-NU activities, and AFP were elevated in primary HCC. We concluded that a new panel can be used to differentiate primary from secondary HC better than AFP, speculating the primary cancer. AFP, LAP, and 5′-NU predominated in primary, while CEA, TGAGs, TSA, and FGA, in secondary HC. Elevation of 5′-NU, LAP, TGAGs, TSA, and FGA to CEA indicated that primary source of HC is CRC. Association of TGAGs, TSA, and FGA only to CEA indicated that the primary cancer is breast. Elevation of TGAGs, TSA, and FGA, with other normal parameters, indicated that the primary cancer is lung. A guiding table is recommended in the oncology laboratory, for management and follow-up, and having more expected level of sensitivity than AFP.

Keywords

Hepatocellular carcinoma Liver metastasis Alpha-fetoprotein glycosaminoglycans Sialic acid 

Notes

Conflict of interest

None

Compliance with ethical standards

We got approval from Minia University research and ethics committee and got written consents for all the participated patients.

References

  1. 1.
    Abbruzzese JL, Abbruzzese MC, Lenzi R, Hess KR, Raber MN. Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. J Clin Oncol. 1995;13:2094–103.CrossRefPubMedGoogle Scholar
  2. 2.
    Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clin Liver Dis. 2005;9:191–211.CrossRefPubMedGoogle Scholar
  3. 3.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  4. 4.
    IuS T. Detection of embryo-specific alpha-globulin in the blood serum of a patient with primary liver cancer. Vopr Med Khim. 1964;10:90–1.Google Scholar
  5. 5.
    Tangkijvanich P, Anukulkarnkusol N, Suwangool P, Lertmaharit S, Hanvivatvong O, Kullavanijaya P, et al. Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol. 2000;31:302–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Zhou L, Liu J, Luo F. Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol. 2006;12:1175–81.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 2008;134:1752–63.CrossRefPubMedGoogle Scholar
  8. 8.
    Zhu K, Dai Z, Pan Q, Wang Z, Yang GH, Yu L, et al. Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res. 2011;17:7294–302.CrossRefPubMedGoogle Scholar
  9. 9.
    Wee A, Nilsson B. Highly well differentiated hepatocellular carcinoma and benign hepatocellular lesions. Can they be distinguished on fine needle aspiration biopsy? Acta Cytol. 2003;47:16–26.CrossRefPubMedGoogle Scholar
  10. 10.
    Schima W, Kulinna C, Langenberger H, Ba-Ssalamah A. Liver metastases of colorectal cancer: US, CT or MR? Cancer Imaging. 2005;5 Spec No A:S149–156.CrossRefPubMedGoogle Scholar
  11. 11.
    Abdel-Hamid N, Farid M, Eldemeri A, Atwa M, Anbar N. Pro-angiogenic mediators as targets for chemotherapy of colorectal carcinoma. Am J Med Med Sci. 2011;1:7–14.CrossRefGoogle Scholar
  12. 12.
    Trinchet JC, Chaffaut C, Bourcier V, Degos F, Henrion J, Fontaine H, et al. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities. Hepatology. 2011;54:1987–97.CrossRefPubMedGoogle Scholar
  13. 13.
    Beard DB, Haskell CM. Carcinoembryonic antigen in breast cancer. Clinical review. Am J Med. 1986;80:241–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Haskell CM, Buchegger F, Schreyer M, Carrel S, Mach JP. Monoclonal antibodies to carcinoembryonic antigen: ionic strength as a factor in the selection of antibodies for immunoscintigraphy. Cancer Res. 1983;43:3857–64.PubMedGoogle Scholar
  15. 15.
    Sardi A, Agnone CM, Nieroda CA, Mojzisik C, Hinkle G, Ferrara P, et al. Radioimmunoguided surgery in recurrent colorectal cancer: the role of carcinoembryonic antigen, computerized tomography, and physical examination. South Med J. 1989;82:1235–44.CrossRefPubMedGoogle Scholar
  16. 16.
    Bates SE. Clinical applications of serum tumor markers. Ann Intern Med. 1991;115:623–38.CrossRefPubMedGoogle Scholar
  17. 17.
    Lee HS, Chung YH, Kim CY. Specificities of serum alpha-fetoprotein in HBsAg+ and HBsAg- patients in the diagnosis of hepatocellular carcinoma. Hepatology. 1991;14:68–72.CrossRefPubMedGoogle Scholar
  18. 18.
    Sato Y, Nakata K, Kato Y, Shima M, Ishii N, Koji T, et al. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med. 1993;328:1802–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Wu JC, Lee SD, Hsiao KJ, Wang SS, Chou P, Tsao D, et al. Mass screening of primary hepatocellular carcinoma by alpha-fetoprotein in a rural area of Taiwan—a dried blood spot method. Liver. 1988;8:100–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Oses JP, Cardoso CM, Germano RA, Kirst IB, Rucker B, Furstenau CR, et al. Soluble NTPDase: an additional system of nucleotide hydrolysis in rat blood serum. Life Sci. 2004;74:3275–84.CrossRefPubMedGoogle Scholar
  21. 21.
    Yegutkin GG. Kinetic analysis of enzymatic hydrolysis of ATP in human and rat blood serum. Biochemistry (Mosc). 1997;62:619–22.Google Scholar
  22. 22.
    Kuang Y, Salem N, Wang F, Schomisch SJ, Chandramouli V, Lee Z. A colorimetric assay method to measure acetyl-CoA synthetase activity: application to woodchuck model of hepatitis virus-induced hepatocellular carcinoma. J Biochem Biophys Methods. 2007;70:649–55.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Martinek RG, Berger L, Broida D. Simplified estimation of leucine aminopeptidase (LAP) activity. Clin Chem. 1964;10:1087–97.PubMedGoogle Scholar
  24. 24.
    Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of the biuret reaction. J Biol Chem. 1949;177:751–66.PubMedGoogle Scholar
  25. 25.
    Elson L, Morgan WT. A colorimetric method for the determination of glucosamine and chondrosamine. Biochem J. 1933;27:1824–8.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Warren L. The thiobarbituric acid assay of sialic acids. J Biol Chem. 1959;234:1971–5.PubMedGoogle Scholar
  27. 27.
    Gold E. A simple spectrophotometric method for estimating glycosaminoglycan concentrations. Anal Biochem. 1979;99:183–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Soresi M, Magliarisi C, Campagna P, Leto G, Bonfissuto G, Riili A, et al. Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Anticancer Res. 2003;23:1747–53.PubMedGoogle Scholar
  29. 29.
    Taketa K, Okada S, Win N, Hlaing NK, Wind KM. Evaluation of tumor markers for the detection of hepatocellular carcinoma in Yangon General Hospital, Myanmar. Acta Med Okayama. 2002;56:317–20.PubMedGoogle Scholar
  30. 30.
    Avila MA, Berasain C, Sangro B, Prieto J. New therapies for hepatocellular carcinoma. Oncogene. 2006;25:3866–84.CrossRefPubMedGoogle Scholar
  31. 31.
    Ward J. New MR, techniques for the detection of liver metastases. Cancer Imaging. 2006;6:33–42.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Fu K, Kobayashi A, Saito N, Sano Y, Kato S, Ikematsu H, et al. Alpha-fetoprotein-producing colon cancer with atypical bulky lymph node metastasis. World J Gastroenterol. 2006;12:7715–6.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Bae JS, Park SJ, Park KB, Paik SY, Ryu JK, Choi CK, et al. Acute exacerbation of hepatitis in liver cirrhosis with very high levels of alpha-fetoprotein but no occurrence of hepatocellular carcinoma. Korean J Intern Med. 2005;20:80–5.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Yao FY. Dramatic reduction of the alpha-fetoprotein level after lamivudine treatment of patients with chronic hepatitis B virus infection and cirrhosis. J Clin Gastroenterol. 2003;36:440–2.CrossRefPubMedGoogle Scholar
  35. 35.
    Tibbetts LM, Doremus CM, Tzanakakis GN, Vezeridis MP. Liver metastases with 10 human colon carcinoma cell lines in nude mice and association with carcinoembryonic antigen production. Cancer. 1993;71:315–21.CrossRefPubMedGoogle Scholar
  36. 36.
    Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001;47:624–30.PubMedGoogle Scholar
  37. 37.
    Nicolini A, Ferrari P, Sagripanti A, Carpi A. The role of tumour markers in predicting skeletal metastases in breast cancer patients with equivocal bone scintigraphy. Br J Cancer. 1999;79:1443–7.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Robertson JF, Jaeger W, Syzmendera JJ, Selby C, Coleman R, Howell A, et al. The objective measurement of remission and progression in metastatic breast cancer by use of serum tumour markers. European Group for Serum Tumour Markers in Breast Cancer. Eur J Cancer. 1999;35:47–53.CrossRefPubMedGoogle Scholar
  39. 39.
    Guadagni F, Ferroni P, Carlini S, Mariotti S, Spila A, Aloe S, et al. A re-evaluation of carcinoembryonic antigen (CEA) as a serum marker for breast cancer: a prospective longitudinal study. Clin Cancer Res. 2001;7:2357–62.PubMedGoogle Scholar
  40. 40.
    Jonsson PE, Bengtsson G, Carlsson G, Jonson G, Tryding N. Value of serum-5-nucleotidase, alkaline phosphatase and gamma-glutamyl transferase for prediction of liver metastases preoperatively in colorectal cancer. Acta Chir Scand. 1984;150:419–23.PubMedGoogle Scholar
  41. 41.
    Pohl AL, Reiner G, Kolb R, Sauermann G, Moser KV, Spona J. Enzyme activities in human breast tumor cells and sera. Cancer Detect Prev. 1985;8:57–66.PubMedGoogle Scholar
  42. 42.
    Pilar M, Ramirez-Exposito MJ, Duenas B, Dolores Mayas M, Jesus Garcia M, De la Chica S, et al. Insulin-regulated aminopeptidase/placental leucil aminopeptidase (IRAP/P-lAP) and angiotensin IV-forming activities are modified in serum of rats with breast cancer induced by N-methyl-nitrosourea. Anticancer Res. 2006;26:1011–4.Google Scholar
  43. 43.
    Yamazaki T, Akada T, Niizeki O, Suzuki T, Miyashita H, Sato Y. Puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) binds and catalyzes PDK1, allowing VEGF-stimulated activation of S6K for endothelial cell proliferation and angiogenesis. Blood. 2004;104:2345–52.CrossRefPubMedGoogle Scholar
  44. 44.
    Cooper EH, Turner R, Steele L, Neville AM, Mackay AM. The contribution of serum enzymes and carcinoembryonic antigen to the early diagnosis of metastatic colorectal cancer. Br J Cancer. 1975;31:111–7.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Ghadge MS, Sirsat AV, Bhansali MS, Desouza LJ, Jagannath P. Leucine amino peptidase a better indicator of carcinoma of liver, biliary tract and pancreas. Indian J Clin Biochem. 2001;16:60–4.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kalathas D, Theocharis DA, Bounias D, Kyriakopoulou D, Papageorgakopoulou N, Stavropoulos MS, et al. Alterations of glycosaminoglycan disaccharide content and composition in colorectal cancer: structural and expressional studies. Oncol Rep. 2009;22:369–75.PubMedGoogle Scholar
  47. 47.
    Auvinen P, Tammi R, Parkkinen J, Tammi M, Agren U, Johansson R, et al. Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival. Am J Pathol. 2000;156:529–36.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Vavetsi R, Bonovas S, Polizou P, Papanastasopoulou C, Dougekou G, Sitaras NM. The diagnostic role of glycosaminoglycans in pleural effusions: a pilot study. BMC Pulm Med. 2009;9:9.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Sanderson RD, Yang Y, Suva LJ, Kelly T. Heparan sulfate proteoglycans and heparanase—partners in osteolytic tumor growth and metastasis. Matrix Biol. 2004;23:341–52.CrossRefPubMedGoogle Scholar
  50. 50.
    Elenius V, Gotte M, Reizes O, Elenius K, Bernfield M. Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1. J Biol Chem. 2004;279:41928–35.CrossRefPubMedGoogle Scholar
  51. 51.
    Topuz E, Tore G, Bilge N, Aldemir O, Kural N, Kinay M, et al. Neuraminic acid (NANA) in the serum as an indicator in breast cancer. Strahlenther Onkol. 1986;162:187–90.PubMedGoogle Scholar
  52. 52.
    Miyata M, Kambe M, Tajima O, Moriya S, Sawaki H, Hotta H, et al. Membrane sialidase NEU3 is highly expressed in human melanoma cells promoting cell growth with minimal changes in the composition of gangliosides. Cancer Sci. 2011;102:2139–49.CrossRefPubMedGoogle Scholar
  53. 53.
    Hogan-Ryan A, Fennelly JJ, Jones M, Cantwell B, Duffy MJ. Serum sialic acid and CEA concentrations in human breast cancer. Br J Cancer. 1980;41:587–92.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Basoglu M, Atamanalp SS, Yildirgan MI, Aydinli B, Ozturk G, Akcay F, et al. Correlation between the serum values of soluble intercellular adhesion molecule-1 and total sialic acid levels in patients with breast cancer. Eur Surg Res. 2007;39:136–40.CrossRefPubMedGoogle Scholar
  55. 55.
    Painbeni T, Gamelin E, Cailleux A, Le Bouil A, Boisdron-Celle M, Daver A, et al. Plasma sialic acid as a marker of the effect of the treatment on metastatic colorectal cancer. Eur J Cancer. 1997;33:2216–20.CrossRefPubMedGoogle Scholar
  56. 56.
    de los Reyes GC, Koda RT, Lien EJ. Glucosamine and chondroitin sulfates in the treatment of osteoarthritis: a survey. Prog Drug Res. 2000;55:81–103.CrossRefPubMedGoogle Scholar
  57. 57.
    Deal CL, Moskowitz RW. Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate. Rheum Dis Clin North Am. 1999;25:379–95.CrossRefPubMedGoogle Scholar
  58. 58.
    Werle B, Kraft C, Lah TT, Kos J, Schanzenbacher U, Kayser K, et al. Cathepsin B in infiltrated lymph nodes is of prognostic significance for patients with nonsmall cell lung carcinoma. Cancer. 2000;89:2282–91.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Nabil Mohie Abdel-Hamid
    • 1
  • M. M. Abouzied
    • 2
  • M. H. Nazmy
    • 2
  • M. A. Fawzy
    • 2
  • A. S. Gerges
    • 3
  1. 1.Biochemistry Department, Faculty of PharmacyKafrelsheikh UniversityKafrelsheikhEgypt
  2. 2.Biochemistry Department, Faculty of PharmacyMinia UniversityMiniaEgypt
  3. 3.Oncology Department, College of MedicineMinia UniversityMiniaEgypt

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