盘点:近期前列腺癌相关机制盘点

2020-08-30 AlexYang MedSci原创

【1】Cell Death & Disease:WFDC2能够抑制前列腺癌的转移

【1】Cell Death & Disease:WFDC2能够抑制前列腺癌的转移 

WFDC2是一个小分子分泌蛋白,在卵巢癌中已有广泛的研究。之前的研究已经证实WFDC2能够促进卵巢癌的增殖和转移,并且可作为诊断生物标记。然而,WFDC2在前列腺癌中的特定功能还未报道。

最近,有研究人员通过生物信息学方法筛选了诊断标记,并发现了良好的预后因子WFDC2。在前列腺癌中,WFDC2的表达于格林森评分和转移呈现负相关关系。体内和体外试验中,WFDC2的过表达和添加重组蛋白HE4能够显著的抑制前列腺癌的转移。免疫共沉淀和共定位试验证明了WFDC2能够结合到上皮生长因子受体(EFGR)的细胞外区域。免疫印迹实验表明WFDC2过表达和添加重组蛋白HE4能够去激活EGFR/AKT/GSK3B/Snail信号途径,之后抑制上皮-间质转化过程。

最后,研究人员指出,他们的研究鉴定了肿瘤抑制子WFDC2能够通过去激活EGFR信号来抑制前列腺癌的转移。

【2】Prostate Cancer P D:5α-还原酶抑制剂治疗患者中PI-RADS评分v.2预测恶性肿瘤情况分析 

最近,有研究人员调查了PI-RADS评分是否在进行5α-还原酶抑制剂(dutasteride)治疗患者中是一种有效的检测前列腺癌的工具,并鉴定了总血清PSA和PSA密度阈值。

研究进行的时间为2015年4月到2018年3月之间,共有75名dutasteride治疗的患者进行了多参数核磁共振(mpMRI)扫描和US/MRI融合前列腺活检。研究共检测到了97个病变位点。在PI-RADS 4-5组中,mpMRI的敏感性和特异性分别为78%和78.7%。阳性预测值(PPV)为79.6%,阴性预测值(NPV)为77.1%。在PI-RADS 3-4-5组,敏感性为100%,特异性为21.3%,PPV为57.5%,NPV为66.77%。在PI-RADS 4-5无活检组中敏感性为82.8%,特异性为80.6%,PPV为80%,NPV为65.6%。PI-RADS 3-4-5无活检组中敏感性为100%,特异性为16.1%,PPV为52.7%,NPV为100%。ROC曲线分析表明了总的血清PSA阈值为6ng/ml(AUC: 0.71;95%CI: 0.60-0.81),PSA密度>0.22(AUC: 0.70;95%CI: 0.6-0.81),使用了推荐前列腺活检的最优截断值。

最后,研究人员指出,PI-RADS评分对dutasteride治疗患者前列腺癌的预测时充分有效的。

【3】Cell Res:Skp2决定了糖酵解和TCA循环之间细胞周期依赖的代谢波动 

葡萄糖主要是通过氧化磷酸化或者糖酵解进行代谢,且在静止细胞与增殖细胞(包括肿瘤细胞)之间存在差异。然而,葡萄糖代谢是如何与哺乳动物细胞的细胞周期进行协同的仍然不清楚。

最近,研究人员表明了哺乳动物细胞在G1期主要利用三羧酸(TCA)循环进行葡萄糖代谢,而在S期更倾向于糖酵解途径。从机制上讲,细胞周期与代谢的耦合主要是通过及时破坏Skp2依赖的关键的TCA循环酶-IDH1/2来实现。因此,SKP2缺乏可破坏IDH1细胞周期依赖性蛋白丰度的波动,并减少S期的糖酵解。更多的是,前列腺癌细胞中Skp2丰度的提高能够去除IDH1的稳定性,从而有利于糖酵解和随后肿瘤的发生。

最后,研究人员指出,细胞周期异常和糖酵解这两个癌症标志之间存在着联系,并阐明了哺乳动物细胞代谢波动与周期性细胞周期的耦合的潜在机制。

【4】Nat Genet:晚期前列腺癌的DNA甲基化情况 

尽管DNA甲基化是基因表达的一个关键调控因子,而转移性癌症的综合甲基化情况还未有鉴定。

最近,有研究人员通过亚硫酸氢盐全基因组测序与全基因组和转录组测序对100个去势抵抗性前列腺转移案例进行了分析,研究发现,能够影响驱使基因的变异只在整合的全基因组方法中检测到。明显的是,研究人员观察到22%的肿瘤表现了新的表观基因组亚型,且与TET2、DNMT3B、IDH1和BRAF的超甲基化和体细胞变异相关。研究人员还鉴定了与致癌基因AR、MYC和ERG的RNA表达相关的基因间隔区的甲基化情况。最后,研究人员还阐释了进展过程中不同的甲基化更倾向于发生在体细胞变异位点和假定的调控区域。

最后,研究人员指出,他们的研究是转移性癌症的全基因组、全甲基组和全转录组测序的大型综合研究,全面概述了甲基化在转移性抗去势前列腺癌中的重要调控作用。

【5】Communications Biology:晚期前列腺癌帐长非编码RNAs与雄激素受体剪接因子相关 

去势抵抗性前列腺癌(CRPC)发展的分子和细胞学机制仍旧不清楚。最近,有研究人员通过使用RNA测序手段分析了编码蛋白RNAs和长非编码蛋白RNAs(lncRNA)的全面和无偏的表达情况,并阐释了CRPC组织中的临床相关分子特性。

研究发现,对那些在CRPC中编码蛋白基因上调的基因,均富集在线粒体相关途径、雄激素受体(AR)和剪接体相关基因。研究人员还发现AR调控的lncRNAs、CRPC-Lncs均在CRPC组织中高表达。明显的是,另两个lncRNAs(CRPC-Lnc #6: PRKAG2-AS1和#9: HOXC-AS1)的沉默能够减弱肿瘤的生长,并能够抑制AR和AR变体的表达。同时,剪接因子U2AF2(在AR的剪接机制中具有必要作用)的亚细胞定位依赖于CRPC-Lnc #6的表达水平。

最后,研究人员指出,他们的调查强调了一部分lncRNAs可作为AR的调控因子,并且也是CRPC的潜在生物标记。

【6】Cell Death & Disease:N-α-乙酰转移酶10蛋白对ADAM9的稳定作用能够促进雄激素非依赖性前列腺癌的进展 

据报道,N-α-乙酰转移酶10蛋白(Naa10p)在雄激素依赖性前列腺癌(PCa;ADPC)中是一个致瘤蛋白,具体是通过结合和增加雄激素受体的转录活性来实现的。PCa通常会从雄激素依赖性阶段发展到雄激素非依赖性阶段,导致了转移和不可治愈可能性的增加。

目前,Naa10p转录本在雄激素非依赖性前列腺癌(AIPC)中还不清楚。最近,有研究人员通过信息学和免疫组化分析表明与临近的征程组织相比,Naa10转录本或者Naa10p蛋白在原发性和转移性PCa癌症组织中高表达。Naa10p在AIPC细胞(DU145和PC-3M)中的敲除或者过表达分别能够减少或者增加细胞克隆和侵袭能力,以及肿瘤的生长和转移能力。蛋白酶芯片筛选鉴定了Naa10p的一个可能的潜在靶标溶解素和金属蛋白酶9 (ADAM9),该蛋白与Naa10p诱导的AIPC细胞的侵袭有关。Naa10p能够与ADAM9形成一个复合物来维持ADAM9的蛋白稳定性,并促进AIPC's的侵袭能力,该过程与其乙酰转移酶活性没有关系。与Naa10p-ADAM9不同的是,ADAM9对Naa10p具有正反馈调控的能力,从而调控AIPC在体内和体外中的进展。

最后,研究人员指出,他们首次阐释了Naa10p与ADAM9在调控AIPC进展中的互作情况。Naa10p与ADAM9互作的破坏是AIPC治疗的一个可能手段。

 

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    2020-09-02 1581f8c42cm

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    2020-09-01 1581f8c42cm

    0

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    2020-08-30 肿肿

    机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1953531, encodeId=d03819535314c, content=<a href='/topic/show?id=b3ec60803a2' target=_blank style='color:#2F92EE;'>#期前列腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60803, encryptionId=b3ec60803a2, topicName=期前列腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4723380, createdName=yangcx0915, createdTime=Fri May 14 06:19:14 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882169, encodeId=fb57882169e8, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200814/81d08245657a4a7f9a1ef713c0ec5878/ec4b201a22194a319b1aeb171bc6bb3d.jpg, createdBy=41e02111625, createdName=1581f8c42cm, createdTime=Wed Sep 02 11:49:45 CST 2020, time=2020-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=881582, encodeId=905888158257, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200814/81d08245657a4a7f9a1ef713c0ec5878/ec4b201a22194a319b1aeb171bc6bb3d.jpg, createdBy=41e02111625, createdName=1581f8c42cm, createdTime=Tue Sep 01 07:08:05 CST 2020, time=2020-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039318, encodeId=5be61039318f0, content=机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Sun Aug 30 17:19:14 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040821, encodeId=51e110408214a, content=前列腺癌相关研究,学习了,谢谢梅斯, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Sun Aug 30 17:19:14 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=880900, encodeId=3a50880900c1, content=好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83erWfbsp4kWWjGYGN5O1RaCgH0mI6m98RIu9fEfHWkpV4NibMbxn6Oaiam5icJOBNzYqOa5juQG5Itj6Q/132, createdBy=35dc2427229, createdName=李纵, createdTime=Sun Aug 30 15:34:36 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=880884, encodeId=e653880884e8, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Sun Aug 30 14:28:18 CST 2020, time=2020-08-30, status=1, ipAttribution=)]
    2020-08-30 misszhang

    前列腺癌相关研究,学习了,谢谢梅斯

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1953531, encodeId=d03819535314c, content=<a href='/topic/show?id=b3ec60803a2' target=_blank style='color:#2F92EE;'>#期前列腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60803, encryptionId=b3ec60803a2, topicName=期前列腺癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4723380, createdName=yangcx0915, createdTime=Fri May 14 06:19:14 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=882169, encodeId=fb57882169e8, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200814/81d08245657a4a7f9a1ef713c0ec5878/ec4b201a22194a319b1aeb171bc6bb3d.jpg, createdBy=41e02111625, createdName=1581f8c42cm, createdTime=Wed Sep 02 11:49:45 CST 2020, time=2020-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=881582, encodeId=905888158257, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200814/81d08245657a4a7f9a1ef713c0ec5878/ec4b201a22194a319b1aeb171bc6bb3d.jpg, createdBy=41e02111625, createdName=1581f8c42cm, createdTime=Tue Sep 01 07:08:05 CST 2020, time=2020-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1039318, encodeId=5be61039318f0, content=机制研究离临床仍然有距离,不过与临床结合思考,仍然有帮助的,不能仅仅是纯临床思维,转化思维同样重要, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=肿肿, createdTime=Sun Aug 30 17:19:14 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1040821, encodeId=51e110408214a, content=前列腺癌相关研究,学习了,谢谢梅斯, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Sun Aug 30 17:19:14 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=880900, encodeId=3a50880900c1, content=好文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83erWfbsp4kWWjGYGN5O1RaCgH0mI6m98RIu9fEfHWkpV4NibMbxn6Oaiam5icJOBNzYqOa5juQG5Itj6Q/132, createdBy=35dc2427229, createdName=李纵, createdTime=Sun Aug 30 15:34:36 CST 2020, time=2020-08-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=880884, encodeId=e653880884e8, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8f435296195, createdName=ms3000000449926787, createdTime=Sun Aug 30 14:28:18 CST 2020, time=2020-08-30, status=1, ipAttribution=)]
    2020-08-30 李纵

    好文章

    0

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    2020-08-30 ms3000000449926787

    学习了

    0

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