肝癌患者E-cadherin基因啟動子區CpG島甲基化狀態的研究_《中國普外基礎與臨床雜志》

作者：

黃文慶 ¹ , 楊文理 ¹ , 柴新娟 ¹ , 陳克霏 ² , 魏玲 ¹ , 李波 ² , 覃揚 ¹

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

關鍵詞：

肝癌 E-cadherin基因 CpG島 DNA甲基化

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的探討抑癌基因E-cadherin基因啟動子區CpG島甲基化與人原發性肝癌（簡稱肝癌）發生、發展的關系，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例未發生肝癌的肝硬變患者的肝硬變組織中E-cadherin基因啟動子區CpG島的甲基化狀態進行檢測。結果E-cadherin基因啟動子區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CpG島甲基化可能在肝癌的發生、發展中起到重要作用，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CpG島甲基化狀態的研究. 中國普外基礎與臨床雜志, 2011, 18(5): 514-519. doi: 復制

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.	Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002 [J]. CA Cancer J Clin, 2005, 55(2): 74108.
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.	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.	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.	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.	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.	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.	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.	Yang X, Yan L, Davidson NE. DNA methylation in breast cancer [J]. Endocr Relat Cancer, 2001, 8(2): 115127.
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.	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.	Taniguchi K, Yamada T, Sasaki Y, et al. Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma [J]. BMC Cancer, 2010, 10: 530.
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.

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. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002 [J]. CA Cancer J Clin, 2005, 55(2): 74108.
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. 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. 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. 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. 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. 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. 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. Yang X, Yan L, Davidson NE. DNA methylation in breast cancer [J]. Endocr Relat Cancer, 2001, 8(2): 115127.
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. 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. Taniguchi K, Yamada T, Sasaki Y, et al. Genetic and epigenetic characteristics of human multiple hepatocellular carcinoma [J]. BMC Cancer, 2010, 10: 530.
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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.

《中國普外基礎與臨床雜志》

肝癌患者E-cadherin基因啟動子區CpG島甲基化狀態的研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

《中國普外基礎與臨床雜志》

肝癌患者E-cadherin基因啟動子區CpG島甲基化狀態的研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料