Significance of DEPDC5 and MICA Variants in Hepatocellular Carcinoma risk related Hepatitis C Virus patients in Egypt
Objectives: Hepatitis C virus (HCV) infection is one of the major causes of hepatocellular carcinoma (HCC) in Egypt. Recently, genetic polymorphisms of DEPDC5 and MICA have been reported to correlate with the progression of HCC in hepatitis C patients. The aim of this study was to determine the relationship between DEPDC5 (rs1012068) T/G, MICA (rs2596542) C/T and the risk of HCC development in patients with HCV infection. Methods: One hundred HCV infected patients suffering from HCC and one hundred healthy controls were enrolled in the current study. Single nucleotide polymorphisms (SNPs) have been studied for DEPDC5 and MICA using real-time PCR. Results: Out of the two genes polymorphisms analyzed, the DEPDC5 and MICA variants were significantly related to the development of HCC (p<0.0001). Only the DEPDC5 variants showed a high (p<0.0001) significant difference in patients with cirrhosis. Moreover, the DEPDC5 variants were significantly correlated with low platelets count (p<0.045). Conclusion: DEPDC5 (rs1012068) and MICA (rs2596542) could be a valuable indicator in diagnosing the progression of liver disease to HCC risk related Hepatitis C Virus patients in Egypt.
1.Villani R, Vendemiale G, Serviddio G. Molecular Mechanisms Involved in HCC Recurrence after Direct-Acting Antiviral Therapy. Int J Mol Sci 2018;20:49. [CrossRef]
2. Abdel-Atti E. HCC Burden in Egypt. Gastroenterol Hepatol 2015;2:45. [CrossRef]
3. Ziada DH, El Sadany S, Soliman H, Abd-Elsalam S, Salama M, Hawash N, et al. Prevalence of hepatocellular carcinoma in chronic hepatitis C patients in Mid Delta, Egypt: A single center study. J Egypt Natl Canc Inst 2016;28:257-62. [CrossRef]
4. Zekri AR, Hassan ZK, Bahnassy AA, Sherif GM, ELdahshan D, Abouelhoda M, et al. Molecular prognostic profile of Egyptian HCC cases infected with hepatitis C virus. Asian Pac J Cancer Prev 2012;13:5433-8. [CrossRef]
5. Shi J, Zhu L, Liu S, Xie W-F. A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. Br J Cancer 2005;92:607-12. [CrossRef]
6. El-Assal M, Al Hassanin S, Hussein A. Epidemiological and clinical characteristics of Egyptian patients with hepatocellular carcinoma: A single center study. Inter J Med Health Sci Res 2015;2:177-86. [CrossRef]
7. Blackard JT, Shata MT, Shire NJ, Sherman KE. Acute hepatitis C virus infection: a chronic problem. Hepatology 2008;47:321- 31. [CrossRef]
8. Maheshwari A, Ray S, Thuluvath PJ. Acute hepatitis C. Lancet 2008;372:321-32. [CrossRef]
9. Chiaramonte M, Stroffolini T, Vian A, Stazi MA, Floreani A, Lorenzoni U, et al. Role of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 1999; 85:2132-7. [CrossRef]
10. Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. Int J Med Sci 2006;3:47-52. [CrossRef]
11. Al-Anazi MR, Matou-Nasri S, Abdo AA, Sanai FM, Khan MQ, Albenmousa A, et al. Variations in DEPDC5 gene and its association with chronic hepatitis C virus infection in Saudi Arabia. BMC Infect Dis 2014;14:632. [CrossRef]
12. Kumar V, Kato N, Urabe Y, Takahashi A, Muroyama R, Hosono N, et al. Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nat Genet 2011;43:455-8. [CrossRef]
13. Miki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, et al. Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nat Genet 2011;43:797-800. [CrossRef]
14. Ishida S, Picard F, Rudolf G, Noe E, Achaz G, Thomas P, et al. Mutations of DEPDC5 cause autosomal dominant focal epilepsies. Nat Genet 2013;45:552-5. [CrossRef]
15. Villanueva A, Chiang DY, Newell P, Peix J, Thung S, Alsinet C, et al. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008;135:1972-83. [CrossRef]
16. Weichhart T, Haidinger M, Katholnig K, Kopecky C, Poglitsch M, Lassnig C, et al. Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells. Blood 2011;117:4273-83. [CrossRef]
17. Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, et al. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 2013;340:1100-6. [CrossRef]
18. Kharrat A, Millevoi S, Baraldi E, Ponting CP, Bork P, Pastore A. Conformational stability studies of the pleckstrin DEP domain: definition of the domain boundaries. Biochim Biophys Acta 1998;1385:157-164. [CrossRef]
19. Kanehira M, Harada Y, Takata R, Shuin T, Miki T, Fujioka T, et al. Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder carcinogenesis. Oncogene 2007;26:6448- 55. [CrossRef]
20. Harada Y, Kanehira M, Fujisawa Y, Takata R, Shuin T, Miki T, et al. Cell-permeable peptide DEPDC1–ZNF224 interferes with transcriptional repression and oncogenicity in bladder cancer cells. Cancer Res 2010;70:5829-39. [CrossRef]
21. Rodriguez-Rodero S, González S, Rodrigo L, Fernández-Morera JL, Martinez-Borra J, López-Vázquez A, et al. Transcriptional regulation of MICA and MICB: a novel polymorphism in MICB promoter alters transcriptional regulation by Sp1. Eur J Immunol 2007;37:1938-53. [CrossRef]
22. Bauer S, Groh V, Wu J, Steinle A, Phillips J, Lanier L, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 1999;285:727-9. [CrossRef]
23. Zhang C, Wang Y, Zhou Z, Zhang J, Tian Z. Sodium butyrate upregulates expression of NKG2D ligand MICA/B in HeLa and HepG2 cell lines and increases their susceptibility to NK lysis. Cancer Immunol Immunother 2009;58:1275-85. [CrossRef]
24. Abdel-Hamid M, Edelman DC, Highsmith WE, Constantine NT. Optimization, assessment, and proposed use of a direct nested reverse transcription-polymerase chain reaction protocol for the detection of hepatitis C virus. J Hum Virol 1997;1:58-65.
25. Bengsch B, Thimme R, Blum HE. Role of host genetic factors in the outcome of hepatitis C virus infection. Viruses 2009;1:104- 25. [CrossRef]
26. Motomura T, Ono Y, Shirabe K, Fukuhara T, Konishi H, Mano Y, et al. Neither MICA nor DEPDC5 genetic polymorphisms correlate with hepatocellular carcinoma recurrence following hepatectomy. HPB Surg 2012;2012:185496. [CrossRef]
27. Ezzikouri S, Benjelloun S, Pineau P. Human genetic variation and the risk of hepatocellular carcinoma development. Hepatol Int 2013;7:820-31. [CrossRef]
28. Abdel-Wahab M, El-Ghawalby N, Mostafa M, Sultan A, ElSadany M, Fathy O, et al. Epidemiology of hepatocellular carcinoma in Lower Egypt, Mansoura gastroenterology center. Hepatogastroenterology 2007;54:157-62.
29. do-Carmo RF, de Almeida DB, Aroucha DC, Vasconcelos LR, de Moraes AC, de Mendonça Cavalcanti Mdo S, et al. Plasma myeloperoxidase levels correlate within chronic hepatitis C. Hum Immunol 2012;73:1127-31. [CrossRef]
30. Ripoll C, Groszmann RJ, Garcia-Tsao G, Bosch J, Grace N, Burroughs A, et al. The Portal Hypertension Collaborative Group. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J Hepatol 2009;50:923-8. [CrossRef]
31. Hanafy AS, Alaa FA, Randa MH. Association of thrombogenic genes polymorphisms with hepatocellular carcinoma in HCV Egyptian patients. Gene 2016;580:37-40. [CrossRef]
32. Hai H, Tamori A, Thuy LTT, Yoshida K, Hagihara A, Kawamura E, et al. Polymorphisms in MICA, but not in DEPDC5, HCP5 or PNPLA3, are associated with chronic hepatitis C-related hepatocellular carcinoma. Sci Rep 2017;7:11912. [CrossRef]
33. Burza MA, Motta BM, Mancina RM, Pingitore P, Pirazzi C, Lepore SM, et al. DEPDC5 variants increase fibrosis progression in Europeans with chronic hepatitis C virus infection. Hepatology 2016;63:418-27. [CrossRef]
34. Bahram S, Bresnahan M, Geraghty DE, Spies T. A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci USA 1994;91:6259-63. [CrossRef]
35. Groh V, Bahram S, Bauer S, Herman A, Beauchamp M, Spies T. Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA 1996;93:12445-50. [CrossRef]
36. Li H, Liu F, Zhu H, Zhou X, Lu J, Chang H, et al. Interaction between polymorphisms of IFN- γ and MICA correlated with hepatocellular carcinoma. Med Sci Monit 2016;22:549-53. [CrossRef]
37. Mohamed AA, Elsaid OM, Amer EA, Elosaily HH, Sleem MI, Gerges SS, et al. Clinical significance of SNP (rs2596542) in histocompatibility complex class I-related gene a promoter region among hepatitis C virus related hepatocellular carcinoma cases. J Adv Res 2017;8:343-9. [CrossRef]
38. Hoshida Y, Fuchs BC, Tanabe KK. Genomic risk of hepatitis Crelated hepatocellular carcinoma. J Hepatol 2012;56:729-30.
39. Chen A, Shen Y, Xia M, Xu L, Pan N, Yin Y, et al. Expression of the nonclassical HLA class I and MICA/B molecules in human hepatocellular carcinoma. Neoplasma 2011;58:371-6. [CrossRef]
40. Abdel-Hamid M, Nada OH, Ellakwa DE, Ahmed LK. Role of Myeloperoxidase in hepatitis C virus related hepatocellular Carcinoma. Meta Gene 2018;18:1-8. [CrossRef]
41. Hussein MR. Alteration of p53, Bcl-2 and hMSH2 protein expression in the cirrhotic, macronegenerative, dysplastic nodules and hepatocellular carcinoma in Upper Egypt. Liver Int 2004;24:552-560. [CrossRef]