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Serum miRNA Panel in Egyptian Patients with Chronic Hepatitis C Related Hepatocellular Carcinoma

  • Khairy, Ahmed (Endemic Medicine Department, Faculty of Medicine, Cairo University) ;
  • Hamza, Iman (Endemic Medicine Department, Faculty of Medicine, Cairo University) ;
  • Shaker, Olfat (Endemic Medicine Department, Faculty of Medicine, Cairo University) ;
  • Yosry, Ayman (Endemic Medicine Department, Faculty of Medicine, Cairo University)
  • Published : 2016.05.01

Abstract

Background: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. MicroRNAs (miRNAs) have great HCC diagnostic potential and circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. Aim: To explore the potential benefit of serum miR-126, miR-129, miR-155, miR-203 and miR-223 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related HCC. Materials and Methods: The expression of miRNA was evaluated using real-time quantitative RT-PCR in 78 serum samples (30 $treatment-na{\ddot{i}}ve$ chronic HCV, 25 post-HCV compensated cirrhosis and 23 $treatment-na{\ddot{i}}ve$ HCC cases). Results: Comparing miRNA fold changes in the HCC group vs the non HCC groups, there was significant fold decrease in miR-126 (P= 0.034), miR-129 (P= 0.006), miR-155 (P= 0.011), miR-203 (P<0.001) and miR-223 (P= 0.013). The highest AUC to differentiate HCC patients from non-HCC was 0.76 for miR-203. Conclusions: Among studied miRNAs, serum miR-203 has the highest potential as a non-invasive biomarker of HCC.

Keywords

HCC diagnosis;chronic HCV infection;serum miRNAs;Egypt

References

  1. Anwar WA, Khaled HM, Amra HA, et al (2008). Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention. Mutat Res, 659, 176-84. https://doi.org/10.1016/j.mrrev.2008.01.005
  2. Borel F, Konstantinova P, Jansen PL (2012). Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. J Hepatol, 56, 1371-83.
  3. Bushati N, Cohen SM (2007). microRNA functions. Annu Rev Cell Dev Biol, 23, 175-205. https://doi.org/10.1146/annurev.cellbio.23.090506.123406
  4. Chen DS, Sung JL, Sheu JC, et al (1984). Serum alpha-fetoprotein in the early stage of human hepatocellular carcinoma. Gastroenterol, 86, 1404-9.
  5. Chen XM (2009). MicroRNA signatures in liver diseases. World J Gastroenterol, 15, 1665-72. https://doi.org/10.3748/wjg.15.1665
  6. Chen X, Zhang L, Zhang T, et al (2013). Methylation-mediated repression of microRNA 129-2 enhances oncogenic SOX4 expression in HCC. Liver Int, 33, 476-86. https://doi.org/10.1111/liv.12097
  7. El-Abd NE, Fawzy NA, El-Sheikh SM, et al (2015). Circulating miRNA-122, miRNA-199a, and miRNA-16 as biomarkers for early detection of hepatocellular carcinoma in egyptian patients with chronic hepatitis C virus infection. Mol Diagn Ther, 19, 213-20. https://doi.org/10.1007/s40291-015-0148-1
  8. Fesler A, Zhai H, Ju J (2014). miR-129 as a novel therapeutic target and biomarker in gastrointestinal cancer. Onco Targets Ther, 21, 1481-5.
  9. Fukao T, Fukuda Y, Kiga K, et al (2007). An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling. Cell, 129, 617-31. https://doi.org/10.1016/j.cell.2007.02.048
  10. Furuta M, Kozaki KI, Tanaka S, et al (2010). miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis, 31, 766-76. https://doi.org/10.1093/carcin/bgp250
  11. Han ZB, Chen HY, Fan JW, et al (2012). Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation. J Cancer Res Clin Oncol, 138, 153-61. https://doi.org/10.1007/s00432-011-1076-z
  12. Huang S, He X (2011). The role of microRNAs in liver cancer progression. Br J Cancer, 104, 235-40. https://doi.org/10.1038/sj.bjc.6606010
  13. Hung CH, Chiu YC, Chen CH, et al (2014). MicroRNAs in hepatocellular carcinoma: carcinogenesis, progression, and therapeutic target. Biomed Res Int, 2014, 486407.
  14. Johnnidis JB, Harris MH, Wheeler RT, et al (2008). Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature, 451, 1125-9. https://doi.org/10.1038/nature06607
  15. Llovet JM, Burroughs A, Bruix J (2003). Hepatocellular carcinoma. Lancet, 362, 1907-17 https://doi.org/10.1016/S0140-6736(03)14964-1
  16. Liu Y, Ren F, Rong M, et al (2015). Association between underexpression of microrna-203 and clinicopathological significance in hepatocellular carcinoma tissues. Cancer Cell Int, 15, 62. https://doi.org/10.1186/s12935-015-0214-0
  17. Lu CY, Lin KY, Tien MT, et al (2013). Frequent DNA methylation of MiR-129-2 and its potential clinical implication in hepatocellular carcinoma. Genes Chromosomes Cancer, 52, 636-43.
  18. Marrero JA, Lok AS (2004). Newer markers for hepatocellular carcinoma. Gastroenterol, 127, 113-9. https://doi.org/10.1053/j.gastro.2004.09.024
  19. Okuda H, Nakanishi T, Takatsu K, et al (2000). Serum levels of des-gamma-carboxy prothrombin measured using the revised enzyme immunoassay kit with increased sensitivity in relation to clinicopathologic features of solitary hepatocellular carcinoma. Cancer, 88, 544-9. https://doi.org/10.1002/(SICI)1097-0142(20000201)88:3<544::AID-CNCR8>3.0.CO;2-F
  20. Omar A, Abou-Alfa GK, Khairy A, et al (2013). Risk factors for developing hepatocellular carcinoma in Egypt. Chin Clin Oncol, 2, 43.
  21. Tateishi R, Yoshida H, Matsuyama Y, et al (2008). Diagnostic accuracy of tumor markers for hepatocellular carcinoma: a systematic review. Hepatol Int, 2, 17-30 https://doi.org/10.1007/s12072-007-9038-x
  22. Wan D, Shen S, Fu S, et al (2015). miR-203 suppresses the proliferation and metastasis of hepatocellular carcinoma by targeting oncogene ADAM9 and oncogenic long non-coding RNA HULC. Anticancer Agents Med Chem. Details?
  23. Wei W, Wanjun L, Hui S, et al (2013). miR-203 inhibits proliferation of HCC cells by targeting survivin. Cell Biochem Funct, 31, 82-5. https://doi.org/10.1002/cbf.2863
  24. Wong QW, Lung RW, Law PT, et al (2008). MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterol, 135, 257-69. https://doi.org/10.1053/j.gastro.2008.04.003
  25. Xu J, Wu C, Che X, et al (2011). Circulating MicroRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog, 50, 136-42. https://doi.org/10.1002/mc.20712
  26. Yu CH, Xu CF, Li YM (2009). Association of microRNA-223 expression with hepatic ischemia/reperfusion injury in mice. Dig Dis Sci, 54, 2362-6. https://doi.org/10.1007/s10620-008-0629-8
  27. Zhang Y, Wei W, Cheng N, et al (2012). Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating wnt signaling. Hepatol, 56, 1631-40. https://doi.org/10.1002/hep.25849