• 1.四川大學華西基礎醫(yī)學與法醫(yī)學院 生物化學與分子生物學實驗室(四川成都610041);;
  • 2.四川大學華西醫(yī)院肝臟血管外科(四川成都 610041);

目的探討抑癌基因E-cadherin基因啟動子區(qū)CpG島甲基化與人原發(fā)性肝癌（簡稱肝癌）發(fā)生、發(fā)展的關系，及其在肝癌早期診斷中的意義。方法用巢式甲基化特異性PCR對34例肝癌患者的癌組織、距離癌灶邊緣 gt;3 cm的遠癌組織及10例未發(fā)生肝癌的肝硬變患者的肝硬變組織中E-cadherin基因啟動子區(qū)CpG島的甲基化狀態(tài)進行檢測。結果E-cadherin基因啟動子區(qū)CpG島甲基化陽性率，在34例肝癌組織中為61.76% (21/34)，明顯高于遠癌組織中的29.41% (10/34)，P lt;0.05; 在10例無肝癌的肝硬變組織中為50.00% (5/10)，與肝癌組織和遠癌組織比較差異均無統(tǒng)計學意義(P gt;0.05); 在4例正常肝組織中均為甲基化陰性。聯(lián)合檢測癌組織E-cadherin基因CpG島甲基化與血清甲胎蛋白兩種分子標志物，肝癌的檢出率可達82.35%。結論抑癌基因E-cadherin啟動子區(qū)CpG島甲基化可能在肝癌的發(fā)生、發(fā)展中起到重要作用，并且可能是早期事件，其在肝癌的臨床診斷及治療中的意義值得進一步深入研究。

引用本文： 黃文慶,楊文理,柴新娟,陳克霏,魏玲,李波,覃揚. 肝癌患者E-cadherin基因啟動子區(qū)CpG島甲基化狀態(tài)的研究. 中國普外基礎與臨床雜志, 2011, 18(5): 514-519. doi: 復制

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  1. 1. Song P, Tang W, Tamura S, et al. The management of hepatocellular carcinoma in Asia: a guideline combining quantitative and qualitative evaluation [J]. Biosci Trends, 2010, 4(6): 283287.
  2. 2. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002 [J]. CA Cancer J Clin, 2005, 55(2): 74108.
  3. 3. Lee TK, Castilho A, Ma S, et al. Liver cancer stem cells: implications for a new therapeutic target [J]. Liver Int, 2009, 29(7): 955965.
  4. 4. Nishida N, Nagasaka T, Nishimura T, et al. Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma [J]. Hepatology, 2008, 47(3): 908918.
  5. 5. Moribe T, Iizuka N, Miura T, et al. Methylation of multiple genes as molecular markers for diagnosis of a small, welldifferentiated hepatocellular carcinoma [J]. Int J Cancer, 2009, 125(2): 388397.
  6. 6. Celebiler Cavusoglu A, Sevinc AI, Saydam S, et al. Promoter methylation and expression changes of CDH1 and P16 genes in invasive breast cancer and adjacent normal breast tissue [J]. Neoplasma, 2010, 57(5): 465472.
  7. 7. Liu RY, Lei Z, Li W, et al. Infrequently methylated event at sites 181 to 9 within the 5′ CpG island of Ecadherin in nonsmall cell lung cancer [J]. Exp Lung Res, 2009, 35(7): 541553.
  8. 8. Yi TZ, Guo J, Zhou L, et al. Prognostic value of Ecadherin expression and CDH1 promoter methylation in patients with endometrial carcinoma [J]. Cancer Invest, 2011, 29(1): 8692.
  9. 9. Yamashita K, Sakuramoto S, Watanabe M. Genomic and epigenetic profiles of gastric cancer: potential diagnostic and therapeutic applications [J]. Surg Today, 2011, 41(1): 2438.
  10. 10. Yang X, Yan L, Davidson NE. DNA methylation in breast cancer [J]. Endocr Relat Cancer, 2001, 8(2): 115127.
  11. 11. Herman JG, Graff JR, Myhnen S, et al. Methylationspecific PCR: a novel PCR assay for methylation status of CpG islands [J]. Proc Natl Acad Sci U S A, 1996, 93(18): 98219826.
  12. 12. Guo M, Ren J, House MG, et al. Accumulation of promoter methylation suggests epigenetic progression in squamous cell carcinoma of the esophagus [J]. Clin Cancer Res, 2006, 12(15): 45154522.
  13. 13. Taniguchi K, Yamada T, Sasaki Y, et al. Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma [J]. BMC Cancer, 2010, 10: 530.
  14. 14. Oh BK, Um TH, Choi GH, et al. Frequent changes in subtelomeric DNA methylation patterns and its relevance to telomere regulation during human hepatocarcinogenesis [J]. Int J Cancer, 2011, 128(4): 857868.
  15. 15. 車向明, 王曙逢, 樊林, 等. Ecadherin 反義寡核苷酸對腫瘤細胞浸潤能力影響的研究 [J]. 中國普外基礎與臨床雜志, 2006,13(2): 191193.
  16. 16. 劉驊, 周敏, 趙文毅, 等. 不同壓強與時程CO2氣腹對胃癌細胞黏附侵襲能力的影響 [J]. 中國普外基礎與臨床雜志, 2010, 17(6): 557561.
  17. 17. Zhai B, Yan HX, Liu SQ, et al. Reduced expression of Ecadherin/catenin complex in hepatocellular carcinomas [J]. World J Gastroenterol, 2008, 14(37): 56655673.
  18. 18. 張友才, 陳金霞, 龔玲, 等. 肝細胞肝癌上皮鈣黏素基因表達和啟動子甲基化研究 [J]. 實用腫瘤雜志, 2008, 23(4): 314317.
  19. 19. Li B, Liu W, Wang L, et al. CpG island methylator phenotype associated with tumor recurrence in tumornodemetastasis stage Ⅰ hepatocellular carcinoma [J]. Ann Surg Oncol, 2010, 17(7): 19171926.
  20. 20. Wang J, Qin Y, Li B, et al. Detection of aberrant promoter methylation of GSTP1 in the tumor and serum of Chinese human primary hepatocellular carcinoma patients [J]. Clin Biochem, 2006, 39(4): 344348.
  21. 21. Tseng RC, Lee SH, Hsu HS, et al. SLIT2 attenuation during lung cancer progression deregulates betacatenin and Ecadherin and associates with poor prognosis [J]. Cancer Res, 2010, 70(2): 543551.
  22. 22. Du GS, Wang JM, Lu JX, et al. Expression of PaPKCiota, Ecadherin, and betacatenin related to invasion and metastasis in hepatocellular carcinoma [J]. Ann Surg Oncol, 2009, 16(6): 15781586.
  23. 23. Zhang XF, Qi X, Meng B, et al. Prognosis evaluation in alphafetoprotein negative hepatocellular carcinoma after hepatectomy: comparison of five staging systems [J]. Eur J Surg Oncol, 2010, 36(8): 718724.
  24. 24. Snowberger N, Chinnakotla S, Lepe RM, et al. Alpha fetoprotein, ultrasound, computerized tomography and magnetic resonance imaging for detection of hepatocellular carcinoma in patients with advanced cirrhosis [J]. Aliment Pharmacol Ther, 2007, 26(9): 11871194.