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The Expressions Of Histone Methyltransferases EZH2and NSD2of Prostate Cancer

Posted on:2014-01-24Degree:MasterType:Thesis
Country:ChinaCandidate:B S ZhengFull Text:PDF
GTID:2234330398488229Subject:Surgery
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[Background and Purpose] Prostate cancer is a kind of malignant tumor ofurogenital system in males, for the graying society and increased expected life span.The morbidity has been also increased in our country in recent years. SerumPSA(Prostate specific antigen) is the only tumor marker used widely for screeningprostate cancer, but PSA has no satisfactory specificity and sensitivity for earlydiagnosis yet. In recent years, So, the problem is to seek a kind of tumor markerwhich has high specificity and sensitivity. Epigenetic modification is a hot spot ofcancer research in recent years, in which, histone modifications attracted researchersattention due to the high diversity and the roles in the regulation of gene expression.The mechanisms of histone modification are post-translation of the N terminus ofhistone through methylation, phosphorylation and acetylation. Those modificationsaffect the interaction between DNA and histones, and make chromatin loose andshrink, then regulate genes transcription. A growing number of studies have shownthat histone methylation transferase plays an important role in tumor development,HMTs active lack or imbalance may be one of the reasons lead to tumorigenesis.EZH2and NSD2are all histone methyltransferases. Researchs found that EZH2is anumber of the famly of PcG and evolutionarily highly conserved gene in and the onlycatalytic enzymes for H3K27methylation, it related to histone modification and playsan important role on cell growth and development, and on tumorigenesis are earlyattention.It is highly expressed in many tumor cell lines, and this high expression isrelated to advancement and prognosis of prostate cancer. NSD is a lysine histone methyltransferase which containing the SET domain, belongs to the members of thefamily of the NSD (nuclear receptor binding SET domain containing) protein, NSD2may catalyze H3K36methylation. In adults, the high expression of NSD2is closelyrelated to many tumors, but the research of NSD2in prostate cancer was rarelyreported. So this study will investigate the following issues: Usingimmunohistochemical techniques and RT-PCR technique to detect the expression ofEZH2and NSD2on protein and mRNA levels on prostate cancer, and discuss theexpression and clinical meaning of EZH2and NSD2in prostate cancer.[Material and method]1. Adenocarcinoma of the prostate from the Affiliatedhospital of Dali college and the People’s hospital of Dali Area were collected betweenJan2002and July2012. All the pathological tissues were divided into three groups:low, media and high risk groups basis on the grade standard of Gleason.30ofProstatic intraepithelial neoplasia and30of benign prostatic hyperplasia were choicerandomly.2. The expression of NSD2and EZH2were investigated on the abovetissues through immunochemistry and RT-PCR and clinical pathological analysis wascarried out.[Results]1.127of adenocarcinoma of the prostate including56of low risk group,age from62to77, the median age is70,23of media risk group, age from59to87,the median age is72, and48of high risk group, age from65to79, the median age is71were collected.2. The EZH2positive ratio is90%(115/127) in adenocarcinoma ofthe prostate,23%(7/30) in benign prostatic hyperplasia and53%(16/30) in Prostaticintraepithelial neoplasia with immunochemical staining. Compared with BPH groupor PIN group, the EZH2expression on adenocarcinoma of the prostate wassignificance(p=0.000respectively). The EZH2positive ratio is91%(51/56) in low risk group,86%(20/23) in media risk group and91%(44/48) in high risk group.Comparing the positive ratio among the three groups, there is no significance (P>0.05). The positive ratio for EZH2is90%(27/30) in adenocarcinoma of the prostate,containing90%(9/10) in low risk group,80%(8/10) in media risk group and100%(10/10) in high risk group and0%(0/10) in benign prostatic hyperplasia with RT-PCR.Compared with BPH group, the EZH2expression in adenocarcinoma of the prostatewas significance(P<0.05). The EZH2expression on mRNA level checking withRT-PCR is similar to protein level checking with immunochemistry staining.3. TheNSD2positive ratio is87%(111/127) in adenocarcinoma of the prostate,6%(2/30) inbenign prostatic hyperplasia and63%(19/30) in Prostatic intraepithelial neoplasiawith immunochemical staining. Compared with BPH group or PIN group, the NSD2expression on adenocarcinoma of the prostate was significance(p=0.000and0.002respectively). The NSD2positive ratio is80%(45/56) in low risk group,91%(21/23)in media risk group and93%(45/48) in high risk group. The positive ratio for NSD2is83%(25/30) in adenocarcinoma of the prostate, containing7%(7/10) in low riskgroup,90%(9/10) in media risk group and90%(9/10) in high risk group and10%(1/10) in benign prostatic hyperplasia with RT-PCR. Compared with BPH group, theNSD2expression in adenocarcinoma of the prostate was significance(P<0.05). TheNSD2expression on mRNA level checking with RT-PCR is similar to protein levelchecking with immunochemistry staining.[Conclusion]1. Comparing with BPH group or PIN group, the EZH2expression onadenocarcinoma of the prostate was higher. There is no significance about EZH2expression among the low, media and high risk groups.2. Compared with BPH group or PIN group, the NSD2expression on adenocarcinoma of the prostate was increasingsignificantly. There is no significance about NSD2expression among the low, mediaand high risk groups. Comparing with BPH group, the expression of NSD2on PINgroup is significance.3. The EZH2and NSD2expression on mRNA level checkingwith RT-PCR is similar to protein level checking with immunochemistry staining.4.The high expression of EZH2and NSD2is closely related to tumorigenesis anddevelopment, and no relationship with the degree of tumor differentiation.5. EZH2and NSD2expression in prostate cancer...
Keywords/Search Tags:Prostate, EZH2, NSD2
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