• 1.山東大學(xué)第二醫(yī)院肛腸外科（山東濟(jì)南 250033）;;
  • 2.山東中醫(yī)藥大學(xué)微循環(huán)實(shí)驗(yàn)室（山東濟(jì)南 250014）;

目的 　探討zeste基因增強(qiáng)子同源物2（EZH2） mRNA在結(jié)直腸癌組織中的表達(dá)及其與結(jié)直腸癌臨床病理特征的關(guān)系。
方法 　采用PCR方法檢測(cè)了27例結(jié)直腸癌患者的癌組織、癌旁組織和正常黏膜上皮組織中EZH2mRNA的表達(dá)情況，并分析其與結(jié)直腸癌臨床病理特征的關(guān)系。
結(jié)果 　結(jié)直腸癌組織、癌旁組織及正常黏膜上皮組織中EZH2mRNA的表達(dá)水平分別為3.01±1.29、1.20±0.69及0.87±0.37，其在結(jié)直腸癌組織的表達(dá)水平最高（P＜0.01），而在癌旁組織和正常黏膜上皮組織中的表達(dá)差異無統(tǒng)計(jì)學(xué)意義（P=0.403）。結(jié)直腸癌組織中EZH2mRNA的表達(dá)與其TNM分期（P=0.002）和組織分化程度（P=0.005）均有關(guān)，與年齡（P=0.388）、性別（P=0.963）、腫瘤直徑（P=0.579）、組織學(xué)類型（P=0.945）、腫瘤位置（P=0.611）及淋巴結(jié)轉(zhuǎn)移（P=0.449）均無關(guān)。
結(jié)論 　EZH2mRNA在結(jié)直腸癌組織中呈高表達(dá)，可能在結(jié)直腸癌的發(fā)生和發(fā)展過程中起關(guān)鍵作用，可作為判斷結(jié)直腸癌惡性程度及進(jìn)程的參考指標(biāo)之一。

引用本文： 呂艷鋒,韓冰冰,禹化龍,王建新. EZH2 mRNA在結(jié)直腸癌組織中的表達(dá)及其臨床意義△. 中國(guó)普外基礎(chǔ)與臨床雜志, 2013, 20(7): 752-755. doi: 復(fù)制

1. Varambally S， Dhanasekaran SM， Zhou M， et al. The polycomb group protein EZH2 is involved in progression of prostate cancer[J]. Nature， 2002， 419(6907)：624-629.
2. Bracken AP， Pasini D， Capra M， et al. EZH2 is downstream of the pRB-E2F pathway， essential for proliferation and amplified in cancer[J]. EMBO J， 2003， 22(20)：5323-5335.
3. Hanson RD， Hess JL， Yu BD， et al. Mammalian trithorax and polycomb-group homologues are antagonistic regulators of homeoticdevelopment[J]. Proc Natl Acad Sci U S A， 1999， 96(25)：14372-14377.
4. Jacobs JJ， van Lohuizen M. Polycomb repression：from cellularmemory to cellular proliferation and cancer[J]. Biochim BiophysActa， 2002， 1602(2)：151-161.
5. Cao R， Wang L， Wang H， et al. Role of histone H3 lysine 27 methylation in polycomb-group silencing[J]. Science， 2002， 298(5595)：1039-1043.
6. Kuzmichev A， Jenuwein T， Tempst P， et al. Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3[J]. Mol Cell， 2004， 14(2)：183-193.
7. Simon JA， Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics[J]. Mutat Res， 2008， 647(1-2)：21-29.
8. Bachmann IM， Halvorsen OJ， Collett K， et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subg-roups in cutaneous melanoma and cancers of the endometrium，prostate， and breast[J]. J Clin Oncol， 2006， 24(2)：268-273.
9. Kozakowski N， Soleiman A， Pammer J. BMI-1 expression is inversely correlated with the grading of renal clear cell carcinoma[J]. Pathol Oncol Res， 2008， 14(1)：9-13.
10. Croonquist PA， Van Ness B. The polycomb group protein enhancerof zeste homolog 2 (EZH2) is an oncogene that influences myelomacell growth and the mutant ras phenotype[J]. Oncogene， 2005， 24(41)：6269-6280.
11. Breuer RH， Snijders PJ， Smit EF， et al. Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis[J]. Neoplasia， 2004， 6(6)：736-743.
12. Weikert S， Christoph F， Köllermann J， et al. Expression levels of the EZH2 polycomb transcriptional repressor correlate with aggressiveness and invasive potential of bladder carcinomas[J]. Int J Mol Med， 2005， 16(2)：349-353.
13. Arisan S， Buyuktuncer ED， Palavan-Unsal N， et al. Increased expression of EZH2， a polycomb group protein， in bladder carcinoma[J]. Urol Int， 2005， 75(3)：252-257.
14. Cardoso C， Mignon C， Hetet G， et al. The human EZH2 gene：genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders[J]. Eur J Hum Genet， 2000， 8(3)：174-180.
15. Tonini T， Bagella L， D’andrilli G， et al. Ezh2 reduces the abilityof HDAC1-dependent pRb2/p130 transcriptional repression of cyclin A[J]. Oncogene， 2004， 23(28)：4930-4937.
16. Sewalt RG， van der Vlag J， Gunster MJ， et al. Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes[J]. Mol Cell Biol， 1998， 18(6)：3586-3595.
17. Collett K， Eide GE， Arnes J， et al. Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer[J]. Clin Cancer Res， 2006， 12(4)：1168-1174.
18. Choi JH， Song YS， Yoon JS， et al. Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasisin gastric cancer[J]. APMIS， 2010， 118(3)：196-202.
19. Matsukawa Y， Semba S， Kato H， et al. Expression of the enha-ncer of zeste homolog 2 is correlated with poor prognosis in humangastric cancer[J]. Cancer Sci， 2006， 97(6)：484-491.
20. Su IH， Basavaraj A， Krutchinsky AN， et al. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement[J]. Nat Immunol， 2003， 4(2)：124-131.
21. Kleer CG， Cao Q， Varambally S， et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells[J]. Proc Natl Acad Sci U S A， 2003， 100(20)：11606-11611.
22. Raaphorst FM， Meijer CJ， Fieret E， et al. Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene[J]. Neoplasia， 2003， 5(6)：481-488.
23. Zetter BR， Banyard J. Cancer. The silence of the genes[J]. Nature， 2002， 419(6907)：572-573.
24. Sun BH， Zhang J， Wang BJ， et al. Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21(WAF1) expression and hepatic apoptosis[J]. World J Gastroenterol， 2000， 6(3)：356-360.
25. Sudo T， Utsunomiya T， Mimori K， et al. Clinicopathological significance of EZH2 mRNA expression in patients with hepatocellular carcinoma[J]. Br J Cancer， 2005， 92(9)：1754-1758.
  1. 1. Varambally S， Dhanasekaran SM， Zhou M， et al. The polycomb group protein EZH2 is involved in progression of prostate cancer[J]. Nature， 2002， 419(6907)：624-629.
  2. 2. Bracken AP， Pasini D， Capra M， et al. EZH2 is downstream of the pRB-E2F pathway， essential for proliferation and amplified in cancer[J]. EMBO J， 2003， 22(20)：5323-5335.
  3. 3. Hanson RD， Hess JL， Yu BD， et al. Mammalian trithorax and polycomb-group homologues are antagonistic regulators of homeoticdevelopment[J]. Proc Natl Acad Sci U S A， 1999， 96(25)：14372-14377.
  4. 4. Jacobs JJ， van Lohuizen M. Polycomb repression：from cellularmemory to cellular proliferation and cancer[J]. Biochim BiophysActa， 2002， 1602(2)：151-161.
  5. 5. Cao R， Wang L， Wang H， et al. Role of histone H3 lysine 27 methylation in polycomb-group silencing[J]. Science， 2002， 298(5595)：1039-1043.
  6. 6. Kuzmichev A， Jenuwein T， Tempst P， et al. Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3[J]. Mol Cell， 2004， 14(2)：183-193.
  7. 7. Simon JA， Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics[J]. Mutat Res， 2008， 647(1-2)：21-29.
  8. 8. Bachmann IM， Halvorsen OJ， Collett K， et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subg-roups in cutaneous melanoma and cancers of the endometrium，prostate， and breast[J]. J Clin Oncol， 2006， 24(2)：268-273.
  9. 9. Kozakowski N， Soleiman A， Pammer J. BMI-1 expression is inversely correlated with the grading of renal clear cell carcinoma[J]. Pathol Oncol Res， 2008， 14(1)：9-13.
  10. 10. Croonquist PA， Van Ness B. The polycomb group protein enhancerof zeste homolog 2 (EZH2) is an oncogene that influences myelomacell growth and the mutant ras phenotype[J]. Oncogene， 2005， 24(41)：6269-6280.
  11. 11. Breuer RH， Snijders PJ， Smit EF， et al. Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis[J]. Neoplasia， 2004， 6(6)：736-743.
  12. 12. Weikert S， Christoph F， Köllermann J， et al. Expression levels of the EZH2 polycomb transcriptional repressor correlate with aggressiveness and invasive potential of bladder carcinomas[J]. Int J Mol Med， 2005， 16(2)：349-353.
  13. 13. Arisan S， Buyuktuncer ED， Palavan-Unsal N， et al. Increased expression of EZH2， a polycomb group protein， in bladder carcinoma[J]. Urol Int， 2005， 75(3)：252-257.
  14. 14. Cardoso C， Mignon C， Hetet G， et al. The human EZH2 gene：genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders[J]. Eur J Hum Genet， 2000， 8(3)：174-180.
  15. 15. Tonini T， Bagella L， D’andrilli G， et al. Ezh2 reduces the abilityof HDAC1-dependent pRb2/p130 transcriptional repression of cyclin A[J]. Oncogene， 2004， 23(28)：4930-4937.
  16. 16. Sewalt RG， van der Vlag J， Gunster MJ， et al. Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes[J]. Mol Cell Biol， 1998， 18(6)：3586-3595.
  17. 17. Collett K， Eide GE， Arnes J， et al. Expression of enhancer of zeste homologue 2 is significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer[J]. Clin Cancer Res， 2006， 12(4)：1168-1174.
  18. 18. Choi JH， Song YS， Yoon JS， et al. Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasisin gastric cancer[J]. APMIS， 2010， 118(3)：196-202.
  19. 19. Matsukawa Y， Semba S， Kato H， et al. Expression of the enha-ncer of zeste homolog 2 is correlated with poor prognosis in humangastric cancer[J]. Cancer Sci， 2006， 97(6)：484-491.
  20. 20. Su IH， Basavaraj A， Krutchinsky AN， et al. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement[J]. Nat Immunol， 2003， 4(2)：124-131.
  21. 21. Kleer CG， Cao Q， Varambally S， et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells[J]. Proc Natl Acad Sci U S A， 2003， 100(20)：11606-11611.
  22. 22. Raaphorst FM， Meijer CJ， Fieret E， et al. Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene[J]. Neoplasia， 2003， 5(6)：481-488.
  23. 23. Zetter BR， Banyard J. Cancer. The silence of the genes[J]. Nature， 2002， 419(6907)：572-573.
  24. 24. Sun BH， Zhang J， Wang BJ， et al. Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21(WAF1) expression and hepatic apoptosis[J]. World J Gastroenterol， 2000， 6(3)：356-360.
  25. 25. Sudo T， Utsunomiya T， Mimori K， et al. Clinicopathological significance of EZH2 mRNA expression in patients with hepatocellular carcinoma[J]. Br J Cancer， 2005， 92(9)：1754-1758.