TMPRSS2／ERG融合基因检测在前列腺癌诊断中的临床应用研究

目的：通过比较TMPRss2／ERG融合基因与前列腺癌各项诊断指标的关系,评估荧光原位杂交技术（FISH）诊断和鉴别诊断前列腺癌的临床应用价值。方法：分别对44例前列腺癌及12例BPH石蜡切片行FIsH检测TMPRSS2和ETS（ERG、ETVl及ETV4）基因融合现象,比较两种疾病发生基因融合的情况,并分析前列腺癌标本中TMPRSS2／ETS基因融合改变和前列腺癌各项诊断指标的关系。结果：在44例前列腺癌标本中,26例（59．1％）检测到MPRSS2／ERG融合基因,4例（9．1％）检测到MPRSS2／ETVl融合基因;l例（2．3％）检测到MPRSS2／ETV4融合基因。20例BPH标本均未检测到基因融合现象。FISH诊断前列腺癌的敏感性为70．5％,特异性为100％。TMPRSS2／ETS基因融合状态异常与Gleason评分和ECT呈正相关,相关系数分别为0．383（P=0．001）和0,309（P=0．041）;MPRSS2／ETS基因异常发生率与DRE和TRUS的阳性检出率无关联（P〉0．05）。结论：FISH技术检测TMPRss2／ETs（ERG、ETVl、ETV4）融合基因在诊断前列腺癌中具有较高的敏感性和特异性,有助于早期前列腺癌的诊断和鉴别诊断。     

融合基因TMPRSS2:ERG与前列腺癌病理分级关系的研究

目的:研究融合基因TMPRSS2:ERG和前列腺癌病理分级的关系。方法:选取前列腺癌的穿刺标本62例为病例组,同时选择10例良性前列腺增生(BPH)患者为对照组,同时纳入9株前列腺癌细胞株作为对照,采用巢式RT-PCR检测融合基因TMPRSS2:ERG,比较融合基因阳性和阴性患者Gleason评分的差异,Logistic回归法分析TMPRSS2:ERG和前列腺癌病理特征的关系。结果:62例前列腺癌患者中有28例检测出TMPRSS2:ERG融合基因,阳性率为45.16%;10例BPH和9株癌细胞株中均未检测出该融合基因。融合基因TMPRSS2:ERG阳性和阴性患者Gleason评分无显著差异(Z=-0.609,P=0.542),但融合基因阳性患者Gleason主评分显著高于阴性患者(Z=-2.600,P=0.009)。单因素Logistic回归分析显示,筛状结构、泡沫状腺体和印戒癌细胞分别与融合基因TMPRSS2:ERG有关联(OR=6.25,P=0.002;OR=6.666,P=0.023;OR=3.24,P=0.035);多因素Logistic回归分析显示,该融合基因和筛状结构有关(OR=3.750,P=0.033)。结论:TMPRSS2:ERG融合基因和前列腺癌中到高级的病理分级有关。     

尿沉淀细胞中TMPRSS2-ETS融合基因对诊断前列腺癌的意义

目的：检测尿沉淀细胞中TMPRSS2-ETS融合基因对诊断前列腺癌的意义。方法：将2010～2011年我院收治的经病理检查证实为前列腺癌者归为前列腺癌组,经病理检查证实为BPH者归为BPH组。收集两组患者前列腺按摩后首次尿液标本,用FISH检测其TMPRSS2-ERG、TMPRSS2ETVl和TMPRSS2-ETV4融合基因的表达。结果：纳入本次研究的前列腺癌组和BPH组分别为51例和20例,TMPRSS2-ERG（＋）的病例分别为26例（50．98％）和4例（20％）,差异有显著统计学意义（P〈O．05）。其敏感度为50．98％,特异度为80％,假阳性率为20％,假阴性率为49．02％,阳性似然比为2．549,阴性似然比为0．613,Youden指数为0．3098。两组中均未发现有TMPRSS2-ETVl或TMPRSS2-ETV4融合基因阳性患者。结论：用FISH方法检测尿沉淀细胞TMPRSS2-ERG融合基因有助于区分前列腺癌与BPH。TMPRSS2-ETV1和TMPRSS2-ETV4融合基因在前列腺癌中出现率较低,故不推荐用于前列腺癌的诊断检测。     

TMPRSS2-ETS融合基因在前列腺癌研究的进展

基因变异是肿瘤发生发展过程中的早期事件。最近发现的TMPRSS2-ETS融合基因对前列腺癌的诊断具有重要意义。TMPRSS2-ETS融合基因具有较高的发生率，并且存在着多种异构体。TMPRSS2-ERG不同融合类型与前列腺癌的临床和病理类型以及前列腺癌的预后都存在着密切的关系，为前列腺癌的诊断、治疗和预后判断提供依据。本文综述TMPRSS2-ETS融合基因与前列腺癌的关系。     

ERG基因及其与前列腺癌关系

因属于ETS转录因子家族,在很多肿瘤中高表达,与肿瘤的血管生成、转移、浸润、抑制凋亡有关,ERG基因在前列腺癌中主要受TMPRSS2-ERG融合基因的调节。近一半以上的前列腺癌病例表达TMPRSS2-ERG融合基因,其中ERG基因可能是前列腺癌的重要标志物,它的检测有助于前列腺癌的诊断和治疗方法的选择。TMPRSS2-ERG融合基因的存在还会影响前列腺癌病人的预后。本文就ERG基因的生物学特征、作用机制、TMPRSS2-ERG的融合机制以及ERG基因与前列腺癌的诊断、治疗和预后的关系作一综述。     

ELL基因在前列腺癌组织中的表达及其意义

目的分析 ELL基因在人类前列腺癌组织中的表达情况,探讨其在前列腺癌发生发展中的作用.方法收集45例前列腺癌组织、15例良性前列腺增生组织和15例正常前列腺组织,提取总 RNA,应用 qRT-PCR检测 ELL mRNA的表达情况,分析其与前列腺癌分级的关系.结果前列腺癌组织中 ELL mRNA 的表达量明显低于良性前列腺增生组织和正常前列腺组织(P＜0．05),而良性前列腺增生组织与正常前列腺组织间差异无统计学意义.随着前列腺癌Gleason评分的升高,ELL mRNA的表达呈下降趋势(P＜0．05).结论 ELL 基因在前列腺癌组织中呈低表达,其表达与前列腺癌的分级密切相关,提示其可能在前列腺癌的发生发展中发挥重要作用.     

前列腺癌TMPRSS2-ETS融合基因的研究进展

<正>前列腺癌是男性常见恶性肿瘤,据统计,前列腺癌发病率在世界范围内位居第二位,其中在欧美国家高居第一位~([1])。前列腺癌发病率有明显的地理和种族差异,欧美国家发病率明显高于亚洲国家。尽管如此,据统计近年来我国前列腺癌发病率明显呈现上升趋势,在北京、上海、广州三城市均已超过男性膀胱癌的发病率,居男性泌尿生殖系肿瘤发病率第一位~([2])。     

融合基因TMPRSS2-ETS对前列腺癌易感性及复发方面的影响研究

随着人口老龄化、生活方式改变等的影响,我国前列腺癌发病率呈明显的上升趋势.前列腺癌的易感因素尚未完全明确,但是其中一些已被公认.其中融合基因TMPRSS2-ETS由于在前列腺癌组织中的特异性、较高的表现率,其在前列腺癌发病机制中的作用及其对前列腺癌易感性的影响受到重视.TMPRSS2-ETS基因融合对前列腺癌易感性的影响表现在其基因融合和生物功能的多样性,决定了TMPRSS2基因和ETS基因二者共同参与了前列腺癌发生、发展和侵袭等多个过程.同时TMPRSS2-ETS基因融合是前列腺癌复发最为重要的关联因子,它的存在可使复发危险性增加.本文就TMPRSS2-ETS融合基因在前列腺癌发病机制中的作用及其对前列腺癌易感性及复发方面的影响作一综述.     

NDRG2基因对前列腺癌细胞株PC-3M侵袭转移能力的影响

目的 观察NDRG2基因对人前列腺癌细胞株PC-3M侵袭转移能力的影响.方法 以携带人NDRG2基因的腺病毒感染体外培养的PC-3M细胞株,采用Western blot及明胶酶谱实验检测NDRG2、MMP-2、MMP-9蛋白表达情况及相关酶活性的变化.平板克隆实验、细胞生长实验检测NDRG2对PC-3M增殖能力的影响.Transwell实验检测NDRG2对PC-3M细胞体外侵袭能力的影响.结果 Ad-NDRG2感染后,PC-3M细胞中NDRG2表达明显增加,而MMP-2和MMP-9表达水平及活性均降低.噻唑蓝(MTT)比色法(抑制率24 h为16.2%、48 h为24.4%、72 h为43.7%)及平板克隆实验(3组分别为56.3%、55.2%和36.7%)显示NDRG2对PC-3M细胞的生长有明显抑制作用.Transwell显示对照组及Ad-LacZ组穿入下室面的细胞数明显多于Ad-NDRG2组(3组分别为93.0、94.8和50.4).结论 NDRG2对人前列腺癌PC-3M细胞株侵袭能力有明显抑制作用,提示NDRG2可能在前列腺癌的侵袭及转移中发挥重要作用.

Abstract：

Objective To investigate the effect of NDRG2 gene expression on the cell migration and invasion of human prostate cancer cell line PC-3M.Methods Recombinant adenovirus vectors carrying human NDRG2 gene (Ad-NDRG2) were infected into prostate cancer cell line PC-3M.The protein expression and enzymatic activities of NDRG2,MMP-2 and MMP-9 were determined by Western blotting and gelatin zymography respectively.Methylthiazol tetrazolium (MTT) assay and plate colony formation were used to determine the effect of proliferation of PC-3M cells.Invasion of PC-3M cells was measured by Transwell chamber assay.Results After infection by Ad-NDRG2,it had been verified that the protein expression of NDRG2 in PC-3M cells was obviously increased,and the expression and enzymatic activities of MMP-2 and MMP-9 were reduced.The MTT assay (inhibition ratio: 24 h,16.2%,48 h,24.4%,and 72 h,43.7% respectively) and plate colony formation (56.3%,55.2% and 36.7% in control group,Ad-LacZ group and Ad-NDGR2 group respectively) revealed that NDRG2 could significantly inhibit the growth and proliferation of PC-3M cells.The number of PC-3M cells that invaded the lower chamber in the Ad-NDRG2 group was significantly decreased as compared with the control group and the Ad-LacZ group (93.0,94.8 and 50.4 respectively).Conclusion NDRG2 gene can significantly inhibit invasion of the PC-3M cells,which may paly an important role in metastasis of prostate cancer.     

A panel of TMPRSS2:ERG fusion transcript markers for urine-based prostate cancer detection with high specificity and sensitivity

Background

The TMPRSS2:ERG fusion is both prevalent and unique to prostate cancer (PCa) and has great potential for noninvasive diagnosis of PCa in bodily fluids.

Objectives

To evaluate the specificity and sensitivity of the TMPRSS2:ERG fusion in urine from diverse clinical contexts and to explore potential clinical applications.

Design, setting, and participants

A total of 101 subjects were enrolled in 2008 from urologic oncology clinics to form three study groups: 44 PCa free, 46 confirmed PCa, and 11 negative prostate biopsies. The PCa-free group included females, healthy young men, and post–radical prostatectomy (RP) patients. The confirmed PCa group was composed of patients under active surveillance, scheduled for treatment, or with metastatic disease.

Measurements

Urine was collected after attentive digital rectal exam (DRE) and coded to blind group allocation for laboratory test. RNA from urine sediments was analyzed using a panel of four TMPRSS2:ERG fusion markers with quantitative polymerase chain reaction (qPCR).

Results and limitations

Our fusion markers demonstrated very high technical specificity and sensitivity for detecting a single fusion-positive cancer cell (VCaP) in the presence of at least 3000 cells in urine sediments. In clinical analysis, there were no fusion-positive samples in the PCa-free group (0 of 44 samples), while there were 16 of 46 (34.8%) fusion-positive samples in the confirmed PCa group. The fusion incidence varied significantly among the three PCa subgroups. The clinical sensitivity increased to 45.4% in cancer patients prior to treatments. The fusion markers were detected in 2 of 11 (18.2%) biopsy-negative patients, suggesting potentially false negative biopsies. This study is not prospective and is limited in sample sizes.

Conclusions

Our novel panel of TMPRSS2:ERG fusion markers provided a very specific and sensitive tool for urine-based detection of PCa. Theses markers can potentially be used to diagnose patients with PCa who have negative biopsies.