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Estimation of Leucine Aminopeptidase and 5-Nucleotidase Increases Alpha-Fetoprotein Sensitivity in Human Hepatocellular Carcinoma Cases

  • Published : 2015.03.04

Abstract

Purpose: To find parameters that can increase alpha-fetoprotein (AFP) sensitivity and so help in accurate diagnosis and rapid management of hepatocullular carcinoma (HCC), as AFP has limited utility of distinguishing HCC from benign hepatic disorders for its high false-positive and false negative rates. Materials and Methods: Serum levels of AFP, 5'-nucleotidase enzyme activity (5-NU) and leucine aminopeptidase enzyme (LAP) activity were measured in 40 individuals. Results: LAP and 5'NU were elevated in HCC at p<0.001. Pearson correlation coefficients showed that changes in AFP exhibited positive correlation with both 5'-NU and LAP at (p<0.001). The complementary use of LAP only with AFP resulted in an increase in sensitivity of AFP from 75% to 90% in detecting HCC. The complementary use of both LAP and 5-NU with AFP resulted in an increased sensitivity of AFP in detecting HCC from 75% to 95%. Conclusions: LAP and 5-FU can be determined in HCC patients in combination with AFP to improve its sensitivity and decrease false negative results.

Keywords

References

  1. Abelev GI, Perova SD, Khramkova NI, et al (1963). Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplantation, 1, 174-80. https://doi.org/10.1097/00007890-196301020-00004
  2. Augusto E, Matos M, Sevigny J, et al (2013). Ecto-5'- nucleotidase (CD73)-mediated formation of adenosine is critical for the striatal adenosine A2A receptor functions. J Neurosci, 33, 11390-9. https://doi.org/10.1523/JNEUROSCI.5817-12.2013
  3. Bae JS, Park SJ, Park KB, et al (2005). Acute exacerbation of hepatitis in liver cirrhosis with very high levels of alphafetoprotein but no occurrence of hepatocellular carcinoma. Korean J Intern Med, 20, 80-5. https://doi.org/10.3904/kjim.2005.20.1.80
  4. Bates SE (1991). Clinical applications of serum tumor markers. Ann Intern Med, 115, 623-38. https://doi.org/10.7326/0003-4819-115-8-623
  5. Bergstrand CG, Czar B (1956). Demonstration of a new protein fraction in serum from the human fetus. Scand J Clin Lab Invest, 8, 174. https://doi.org/10.3109/00365515609049266
  6. Bertino G, Ardiri A, Malaguarnera M, et al (2012). Hepatocellualar carcinoma serum markers. Semin Oncol, 39, 410-33. https://doi.org/10.1053/j.seminoncol.2012.05.001
  7. Carr BI, Guerra V, Giannini EG, et al (2014). Significance of platelet and AFP levels and liver function parameters for HCC size and survival. Int J Biol Markers, 29, e215-23.
  8. Chatterjee SK, Kim U, Bielat K (1976). Plasma membrane associated enzymes of mammary tumours as the biochemical indicators of metastasizing capacity. Analyses of enriched plasma membrane preparations. Br J Cancer, 33, 15-26. https://doi.org/10.1038/bjc.1976.3
  9. El-Attar HA, Kandil MH, El-Kerm YM, et al (2010). Comparison of serum survivin and alpha fetoprotein in Egyptian patients with hepatocellular carcinoma associated with hepatitis C viral infection. Asian Pac J Cancer Prev, 11, 897-903.
  10. El-Serag HB, Marrero JA, Rudolph L, et al (2008). Diagnosis and treatment of hepatocellular carcinoma. Gastroenterol, 134, 1752-63. https://doi.org/10.1053/j.gastro.2008.02.090
  11. Fausther M, Sheung N, Saiman Y, et al (2012). Activated hepatic stellate cells upregulate transcription of ecto-5'-nucleotidase/ CD73 via specific SP1 and SMAD promoter elements. Am J Physiol Gastrointest Liver Physiol, 303, 904-14. https://doi.org/10.1152/ajpgi.00015.2012
  12. Gan Y, Liang Q, Song X (2014). Diagnostic value of alpha-Lfucosidase for hepatocellular carcinoma: a meta-analysis. Tumour Biol, 35, 3953-60. https://doi.org/10.1007/s13277-013-1563-8
  13. Gao J, Xie L, Yang WS, et al (2012). Risk factors of hepatocellular carcinoma--current status and perspectives. Asian Pac J Cancer Prev, 13, 743-52. https://doi.org/10.7314/APJCP.2012.13.3.743
  14. Gornall AG, Bardawill CJ, David MM (1949). Determination of serum proteins by means of the biuret reaction. J Biol Chem, 177, 751-66.
  15. Hunsucker SA, Mitchell BS, Spychala J (2005). The 5'-nucleotidases as regulators of nucleotide and drug metabolism. Pharmacol Ther, 107, 1-30. https://doi.org/10.1016/j.pharmthera.2005.01.003
  16. IuS T (1964). Detection of embryo-specific alpha-globulin in the blood serum of a patient with primary liver cancer. Vopr Med Khim, 10, 90-1 (in Russian).
  17. Kuang Y, Salem N, Wang F, et al (2007). A colorimetric assay method to measure acetyl-CoA synthetase activity: application to woodchuck model of hepatitis virus-induced hepatocellular carcinoma. J Biochem Biophys Methods, 70, 649-55. https://doi.org/10.1016/j.jbbm.2007.02.008
  18. Lee HS, Chung YH, Kim CY (1991). Specificities of serum alpha-fetoprotein in HBsAg+ and HBsAg- patients in the diagnosis of hepatocellular carcinoma. Hepatol, 14, 68-72. https://doi.org/10.1002/hep.1840140112
  19. Llovet JM, Pena CE, Lathia CD, et al (2012). Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clin Cancer Res, 18, 2290-300. https://doi.org/10.1158/1078-0432.CCR-11-2175
  20. Lok AS, Sterling RK, Everhart JE, et al (2010). Des-gammacarboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterol, 138, 493-502. https://doi.org/10.1053/j.gastro.2009.10.031
  21. Malaguarnera G, Giordano M, Paladina I, et al (2010). Serum markers of hepatocellular carcinoma. Dig Dis Sci, 55, 2744-55. https://doi.org/10.1007/s10620-010-1184-7
  22. Martinek RG, Berger L, Broida D (1964). Simplified Estimation of Leucine Aminopeptidase (Lap) Activity. Clin Chem, 10, 1087-97.
  23. Matsui M, Fowler JH, Walling LL (2006). Leucine aminopeptidases: diversity in structure and function. Biol Chem, 387, 1535-44.
  24. Mazzon C, Rampazzo C, Scaini MC, et al (2003). Cytosolic and mitochondrial deoxyribonucleotidases: activity with substrate analogs, inhibitors and implications for therapy. Biochem Pharmacol, 66, 471-9. https://doi.org/10.1016/S0006-2952(03)00290-9
  25. Mittal A, Sathian B, Chandrashekharan N, et al (2011). Diagnostic significance of alpha fetoprotein in carcinomas of liver and biliary tract - a comparative study from the western region of Nepal. Asian Pac J Cancer Prev, 12, 3475-8.
  26. Mizutani S, Shibata K, Kikkawa F, et al (2007). Essential role of placental leucine aminopeptidase in gynecologic malignancy. Expert Opin Ther Targets, 11, 453-61. https://doi.org/10.1517/14728222.11.4.453
  27. Oses JP, Cardoso CM, Germano RA, et al (2004). Soluble NTPDase: An additional system of nucleotide hydrolysis in rat blood serum. Life Sci, 74, 3275-84. https://doi.org/10.1016/j.lfs.2003.11.020
  28. Richardson P, Duan Z, Kramer J, et al (2012). Determinants of serum alpha-fetoprotein levels in hepatitis C-infected patients. Clin Gastroenterol Hepatol, 10, 428-33. https://doi.org/10.1016/j.cgh.2011.11.025
  29. Sangro B, Salem R, Kennedy A, et al (2011). Radioembolization for hepatocellular carcinoma: a review of the evidence and treatment recommendations. Am J Clin Oncol, 34, 422-31. https://doi.org/10.1097/COC.0b013e3181df0a50
  30. Sathe SB, Taskar SP (1982). Leucine amino peptidase levels in hepatic and certain gastro intestinal tract cancers. J Assoc Physicians India, 30, 83.
  31. Sato Y, Nakata K, Kato Y, et al (1993). Early recognition of hepatocellular carcinoma based on altered profiles of alphafetoprotein. N Engl J Med, 328, 1802-6. https://doi.org/10.1056/NEJM199306243282502
  32. Schieving JH, de Vries M, van Vugt JM, et al (2014). Alphafetoprotein, a fascinating protein and biomarker in neurology. Eur J Paediatr Neurol, 18, 243-8. https://doi.org/10.1016/j.ejpn.2013.09.003
  33. Soresi M, Magliarisi C, Campagna P, et al (2003). Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Anticancer Res, 23, 1747-53.
  34. Taketa K (1990). Alpha-fetoprotein: reevaluation in hepatology. Hepatol, 12, 1420-32. https://doi.org/10.1002/hep.1840120625
  35. Tangkijvanich P, Anukulkarnkusol N, Suwangool P, et al (2000). Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol, 31, 302-8. https://doi.org/10.1097/00004836-200012000-00007
  36. Tian L, Wang Y, Xu D, et al (2011). Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases. Int J Cancer, 129, 1923-31. https://doi.org/10.1002/ijc.25838
  37. Tian SY, Chen SH, Shao BF, et al (2014). Expression of leucine aminopeptidase 3 (LAP3) correlates with prognosis and malignant development of human hepatocellular carcinoma (HCC). Int J Clin Exp Pathol, 7, 3752-62.
  38. Trinchet JC, Chaffaut C, Bourcier V, et al (2011). Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities. Hepatology, 54, 1987-97. https://doi.org/10.1002/hep.24545
  39. Tripathi V, Shen Z, Chakraborty A, et al (2013). Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet, 9, 1003368. https://doi.org/10.1371/journal.pgen.1003368
  40. Wang NY, Wang C, Li W, et al (2014). Prognostic value of serum AFP, AFP-L3, and GP73 in monitoring short-term treatment response and recurrence of hepatocellular carcinoma after radiofrequency ablation. Asian Pac J Cancer Prev, 15, 1539-44. https://doi.org/10.7314/APJCP.2014.15.4.1539
  41. Wu JC, Lee SD, Hsiao KJ, et al (1988). Mass screening of primary hepatocellular carcinoma by alpha-fetoprotein in a rural area of Taiwan--a dried blood spot method. Liver, 8, 100-4.
  42. Xu J, Liu C, Zhou L, et al (2012). Distinctions between clinicopathological factors and prognosis of alphafetoprotein negative and positive hepatocelluar carcinoma patients. Asian Pac J Cancer Prev, 13, 559-62. https://doi.org/10.7314/APJCP.2012.13.2.559
  43. Xu J, Liu C, Zhou L, et al (2012). Distinctions between clinicopathological factors and prognosis of alphafetoprotein negative and positive hepatocelluar carcinoma patients. Asian Pac J Cancer Prev, 13, 559-62. https://doi.org/10.7314/APJCP.2012.13.2.559
  44. Yegutkin GG (1997). Kinetic analysis of enzymatic hydrolysis of ATP in human and rat blood serum. Biochemistry, 62, 619-22.
  45. Zhai X, Zhu H, Wang W, et al (2014). Abnormal expression of EMT-related proteins, S100A4, vimentin and E-cadherin, is correlated with clinicopathological features and prognosis in HCC. Med Oncol, 31, 970. https://doi.org/10.1007/s12032-014-0970-z
  46. Zhou L, Liu J, Luo F (2006). Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol, 12, 1175-81. https://doi.org/10.3748/wjg.v12.i8.1175
  47. Zhu K, Dai Z, Pan Q, et al (2011). Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition. Clin Cancer Res, 17, 7294-302. https://doi.org/10.1158/1078-0432.CCR-11-1327

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