Expression and Clinical Value of EZH2 mRNA in Colorectal Cancer Tissues_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LU Yanfeng ¹ , HAN Bingbing ² , YU Hualong ¹ ,  WANG Jianxin. ¹

1.Department of Anoproctology， The Second Hospital of Shandong University， Jinan 250033， Shandong Province， China;;
2.Microcirculation Laboratory， Shangdong University of Traditional Chinese Medicine， Jinan 250014， Shandong Province， China;

Corresponding author：

WANG Jianxin., Email: bjllxhyyw@sina.com

Keywords：

Enhancer of zeste homolog 2; Colorectal cancer; Gene; Expression

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To investigate the expression of enhancer of zeste homolog 2 （EZH2） mRNA in colorectal cancer tissues， and to explore the relationship with clinicopathological features of it.
Methods 　PCR was used to examine the expression of EZH2 mRNA in colorectal cancer tissues， paracancerous tissues， and normal epithelium tissues of 27 patients with colorectal cancer. Meanwhile， the relationship between the expression of EZH2 mRNA and clinicopathological features of colorectal cancer were analyzed.
Results 　Expression level of EZH2 mRNA in colorectal cancer tissues， paracancerous tissues， and normal epithelium tissues were 3.01±1.29， 1.20±0.69， and 0.87±0.37 respectively， and the expression value of colorectal cancer tissues at the top （P＜0.01）， but there were no significant difference between the paracancerous tissues and normal epithelium tissues （P=0.403）. Expression of EZH2 mRNA were related to TNM stages （P=0.002） and degree of differentiation （P=0.005）， but were not related to age （P=0.388）， gender （P=0.963）， diameter of tumor （P=0.579）， histological type （P=0.945）， location of tumor （P=0.611）， and lymph node metastasis （P=0.449）.
Conclusions 　EZH2 mRNA expresses highly in colorectal cancer tissues， so it may play an essential role in the emergence and development of colorectal cancer. EZH2 mRNA can be used as one of the referenced indexes to determine the malignant degree and process of colorectal cancer.

Citation： LU Yanfeng,HAN Bingbing,YU Hualong,WANG Jianxin.. Expression and Clinical Value of EZH2 mRNA in Colorectal Cancer Tissues. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2013, 20(7): 752-755. doi: Copy

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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.
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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. 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression and Clinical Value of EZH2 mRNA in Colorectal Cancer Tissues

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