DOI QR코드

DOI QR Code

Hypermethylation of Suppressor of Cytokine Signaling 1 in Hepatocellular Carcinoma Patients

  • Saelee, Pensri (Research Division, National Cancer Institute) ;
  • Chuensumran, Ubol (Department of Food Science and Technology, School of Culinary Arts, Suan Dusit Rajabhat University) ;
  • Wongkham, Sopit (Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Chariyalertsak, Sunanta (Research Division, National Cancer Institute) ;
  • Tiwawech, Danai (Research Division, National Cancer Institute) ;
  • Petmitr, Songsak (Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University)
  • Published : 2012.07.31

Abstract

Hepatocellular carcinoma (HCC), the most common primary hepatic tumor, is highly prevalent in the Asia-Pacific region, including Thailand. Many genetic and epigenetic alterations in HCC have been elucidated. The aim of this study was to determine whether aberrant methylation of the suppressor of cytokine signaling 1 gene (SOCS1) occurs in HCCs. Methylation specific-PCR assays were performed to identify the methylation status of SOCS1 in 29 tumors and their corresponding normal liver tissues. An abnormal methylation status was detected in 17 (59%), with a higher prevalence of aberrant SOCS1 methylation significantly correlating with HCC treated without chemotherapy (OR=0.04, 95%CI=0.01-0.31; P=0.001). This study suggests that epigenetic aberrant SOCS1 methylation may be a predictive marker for HCC patients.

Keywords

References

  1. Arii S, Sata M, Sakamoto M, et al (2010). Management of hepatocellular carcinoma: report of consensus meeting in the 45th annual meeting of the japan society of hepatology (2009). Hepatol Res, 40, 667-85. https://doi.org/10.1111/j.1872-034X.2010.00673.x
  2. Brakensiek K, Langer F, Schlegelberger B, et al (2005). Hypermethylation of the suppressor of cytokine signalling-1 (SOCS-1) in myelodysplastic syndrome. Br J Haematol, 130, 209-17. https://doi.org/10.1111/j.1365-2141.2005.05590.x
  3. Brysha M, Zhang JG, Bertolino P, et al (2001). Suppressor of cytokine signaling-1 attenuates the duration of interferon gamma signal transduction in vitro and in vivo. J Biol Chem, 276, 22086-9. https://doi.org/10.1074/jbc.M102737200
  4. Edmonson HA, Steiner PE (1954). Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer, 7, 462-503. https://doi.org/10.1002/1097-0142(195405)7:3<462::AID-CNCR2820070308>3.0.CO;2-E
  5. Endo TA, Masuhara M, Yokouchi M, et al (1997). A new protein containing an SH2 domain that inhibits JAK kinases. Nature, 387, 921-4. https://doi.org/10.1038/43213
  6. Fischer JR, Ohnmacht U, Rieger N, et al (2007). Prognostic significance of RASSF1A promoter methylation on survival of non-small cell lung cancer patients treated with gemcitabine. Lung Cancer, 56, 115-23. https://doi.org/10.1016/j.lungcan.2006.11.016
  7. Herman JG, Graff JR, Myohanen S, et al (1996). Methylation-specific PCRa novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A, 93, 9821-6. https://doi.org/10.1073/pnas.93.18.9821
  8. Herman JG, Latif F, Weng Y, et al (1994). Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci U S A, 91, 9700-4. https://doi.org/10.1073/pnas.91.21.9700
  9. Kim DS, Kim MJ, Lee JY, et al (2007). Aberrant methylation of E-cadherin and H-cadherin genes in nonsmall cell lung cancer and its relation to clinicopathologic features. Cancer, 110, 2785-92. https://doi.org/10.1002/cncr.23113
  10. Kim YT, Park JY, Jeon YK, et al (2009). Aberrant promoter CpG island hypermethylation of the adenomatosis polyposis coli gene can serve as a good prognostic factor by affecting lymph node metastasis in squamous cell carcinoma of the esophagus. Dis Esophagus, 22, 143-50. https://doi.org/10.1111/j.1442-2050.2008.00862.x
  11. Ko E, Kim SJ, Joh JW, et al (2008). CpG island hypermethylation of SOCS-1 gene is inversely associated with HBV infection in hepatocellular carcinoma. Cancer Lett, 271, 240-50. https://doi.org/10.1016/j.canlet.2008.06.009
  12. Koelsche C, Strebovsky J, Baetz A, et al (2009). Structural and functional analysis of a nuclear localization signal in SOCS1. Mol Immunol, 46, 2474-80. https://doi.org/10.1016/j.molimm.2009.05.020
  13. Komazaki T, Nagai H, Emi M, et al (2004). Hypermethylation-associated inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human pancreatic cancers. Jpn J Clin Oncol, 34, 191-4. https://doi.org/10.1093/jjco/hyh035
  14. Krtolica K, Krajnovic M, Usaj-Knezevic S, et al (2007). Comethylation of p16 and MGMT genes in colorectal carcinoma: correlation with clinicopathological features and prognostic value. World J Gastroenterol, 13, 1187-94. https://doi.org/10.3748/wjg.v13.i8.1187
  15. Kuroki T, Trapasso F, Yendamuri S, et al (2003). Promoter hypermethylation of RASSF1A in esophageal squamous cell carcinoma. Clin Cancer Res, 9, 1441-5.
  16. Lee S, Cho NY, Yoo EJ, et al (2008). CpG island methylator phenotype in colorectal cancers: comparison of the new and classic CpG island methylator phenotype marker panels. Arch Pathol Lab Med, 132, 1657-65.
  17. Lehmann U, Wingen LU, Brakensiek K, et al (2007). Epigenetic defects of hepatocellular carcinoma are already found in non-neoplastic liver cells from patients with hereditary haemochromatosis. Hum Mol Genet, 16, 1335-42. https://doi.org/10.1093/hmg/ddm082
  18. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real- time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  19. McClune AC, Tong MJ (2010). Chronic hepatitis B and hepatocellular carcinoma. Clin Liver Dis, 14, 461-76. https://doi.org/10.1016/j.cld.2010.05.009
  20. Miller SA, Dykes DD, Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res, 16, 1215. https://doi.org/10.1093/nar/16.3.1215
  21. Naka T, Narazaki M, Hirata M, et al (1997). Structure and function of a new STAT-induced STAT inhibitor. Nature, 387, 924-9. https://doi.org/10.1038/43219
  22. Okochi O, Hibi K, Sakai M, et al (2003). Methylation-mediated silencing of SOCS-1 gene in hepatocellular carcinoma derived from cirrhosis. Clin Cancer Res, 9, 5295-8.
  23. Oshimo Y, Kuraoka K, Nakayama H, et al (2004). Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma. Int J Cancer, 112, 1003-9. https://doi.org/10.1002/ijc.20521
  24. Ramirez JL, Rosell R, Taron M, et al (2005). 14-3-3sigma methylation in pretreatment serum circulating DNA of cisplatin-plus-gemcitabine-treated advanced non-small-cell lung cancer patients predicts survival. The Spanish Lung Cancer Group. J Clin Oncol, 23, 9105-12. https://doi.org/10.1200/JCO.2005.02.2905
  25. Sporri B, Kovanen PE, Sasaki A, et al (2001). JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling. Blood, 97, 221-6. https://doi.org/10.1182/blood.V97.1.221
  26. Starr R, Willson TA, Viney EM, et al (1997). A family of cytokine-inducible inhibitors of signalling. Nature, 387, 917-21. https://doi.org/10.1038/43206
  27. Ward AC, Touw I, Yoshimura A (2000). The Jak-Stat pathway in normal and perturbed hematopoiesis. Blood, 95, 19-29.
  28. Whittaker S, Marais R, Zhu AX (2010). The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene, 29, 4989-5005. https://doi.org/10.1038/onc.2010.236
  29. Wong IH (2001). Methylation profiling of human cancers in blood: molecular monitoring and prognostication (review). Int J Oncol, 19, 1319-24.
  30. Yang B, Guo M, Herman JG, et al (2003). Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol, 163, 1101-7. https://doi.org/10.1016/S0002-9440(10)63469-4
  31. Yoshida T, Ogata H, Kamio M, et al (2004). SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. J Exp Med, 199, 1701-7. https://doi.org/10.1084/jem.20031675

Cited by

  1. Silencing of Suppressor of Cytokine Signaling-3 due to Methylation Results in Phosphorylation of STAT3 in Imatinib Resistant BCR-ABL Positive Chronic Myeloid Leukemia Cells vol.15, pp.11, 2014, https://doi.org/10.7314/APJCP.2014.15.11.4555
  2. Role of P14 and MGMT Gene Methylation in Hepatocellular Carcinomas: a Meta-analysis vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6591
  3. DNA methylation: potential biomarker in Hepatocellular Carcinoma vol.2, pp.1, 2014, https://doi.org/10.1186/2050-7771-2-5