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Cell：新“致癌”理论：氮代谢紊乱

2018-08-15 小通 生物通

氮代谢癌组织突变
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《Cell》发文指出，对许多类型的癌症患者来说，病人的氮代谢被篡改了，体液中产生了可检出的变化，并有助于癌组织内新突变的形成。短期内，这项发现可促进癌症早期诊断，以及预测免疫疗法成效。

《Cell》发文指出，对许多类型的癌症患者来说，病人的氮代谢被篡改了，体液中产生了可检出的变化，并有助于癌组织内新突变的形成。短期内，这项发现可促进癌症早期诊断，以及预测免疫疗法成效。



氮（N）是人体所有蛋白质、RNA和DNA的基本组成部分，癌细胞对这个元素非常贪婪。魏茨曼科学研究所的研究人员与国家癌症研究所等其他机构的同事合作，在《Cell》发文指出，对许多类型的癌症患者来说，病人的氮代谢被篡改了，体液中产生了可检出的变化，并有助于癌组织内新突变的形成。短期内，这项发现可促进癌症早期诊断，以及预测免疫疗法成效。

人体利用氮，生成含氮废物，通常被称为尿素，尿素在肝脏中发生的一系列生化反应被称为尿素循环，该循环将尿素排入IBD%E8%AF%8A%E6%B2%BB%E8%BF%87%E7%A8%8B%E4%B8%AD%E7%9A%84%E8%AF%84%E4%BC%B0-Part%202" target="_blank">血液，然后随尿液排出体外。魏茨曼生物调节系的Ayelet Erez博士在之前的研究中指出，在许多癌性肿瘤中，尿素循环中的一种酶被失活了，从而增加了用于合成嘧啶的氮的可用性，作为RNA和DNA基块，癌细胞生长需要充足的嘧啶储备。

与国家癌症研究所的Eytan Ruppin教授合作，Erez课题组在新研究中鉴定了一组除了尿素循环酶以外的精确定义酶，这些酶的共同作用增加了含氮化合物产量，使肿瘤的嘧啶水平升高，更易发生突变。

研究人员改变了小鼠结肠癌肿瘤的尿素循环酶表达，与对照组相比，这些小鼠IBD%E8%AF%8A%E6%B2%BB%E8%BF%87%E7%A8%8B%E4%B8%AD%E7%9A%84%E8%AF%84%E4%BC%B0-Part%202" target="_blank">血液中尿素水平降低，尿液中检出一定水平的嘧啶。接下来，他们对100名儿科癌症患者病历进行调查，以评估它们的尿素水平。“我们发现，相比同龄健康儿童，患儿入院当天的血液中尿素水平明显较低，”Erez说。

这些结果表明，肝脏和肿瘤组织尿素循环失调关联氮相关标志物，这将有助于癌症的早期诊断，未来的检测可能依赖一个得分，将血液中的尿素水平和尿液中的嘧啶水平与癌症潜伏挂钩。

“癌细胞不浪费任何东西。过去，我们认为尿液中尿素含量高是一个患病指标，现在含量过低也可能有问题，”Erez说。“癌细胞需要尽可能多的氮，这使它们无法掩饰自己像正常细胞那样看待尿素。”

基于大量癌症基因组数据，研究人员发现，实际上许多癌症类型都存在氮素循环失调，而且伴随嘧啶合成增加导致的特异性突变。

嘧啶相关突变是一把双刃剑：一方面它使癌症更具攻击性，降低患者存活率，另一方面，它也会产生蛋白质片段，使肿瘤在免疫系统眼皮底下“更显眼”。因此，理论上尿素失调的肿瘤患者更适合免疫疗法。调查黑色素瘤患者治疗数据，尿素循环酶失调的肿瘤患者确实比没有这些特征的患者更容易对免疫疗法作出反应。当研究人员诱导小鼠体内癌性肿瘤尿素循环酶失调时，这些小鼠比携带患者肿瘤但酶活正常的小鼠的免疫治疗反应好得多。

相比更复杂的基因组分析，基于活检染色的测试也许更能预测患者免疫治疗的成功几率。

“一个值得探讨的问题是，在免疫治疗前，肿瘤诱导失调的基因操作竟然可以提高免疫治疗有效性，”Erez说。“那么，涉及故意破坏肿瘤尿素循环的操作，是否可以帮助免疫系统识别和破坏肿瘤呢？”

原始出处：Lee JS1, Adler L2, Karathia H3, et al. Urea Cycle Dysregulation Generates Clinically Relevant Genomic and Biochemical Signatures. Cell. 2018 Aug 6. pii: S0092-8674(18)30913-9. 

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    2018-10-18 huperzia

    #氮代谢#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2078813, encodeId=767320e8813e4, content=<a href='/topic/show?id=a07d640e05a' target=_blank style='color:#2F92EE;'>#氮代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64070, encryptionId=a07d640e05a, topicName=氮代谢)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca89104, createdName=huperzia, createdTime=Thu Oct 18 10:01:00 CST 2018, time=2018-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870810, encodeId=fc9a18e08104b, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Jul 01 06:01:00 CST 2019, time=2019-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961080, encodeId=c10f19610806a, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Apr 19 10:01:00 CST 2019, time=2019-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370954, encodeId=966e13e095405, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Fri Aug 17 01:01:00 CST 2018, time=2018-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338749, encodeId=94ca338e49f9, content=嗯嗯，学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/07/16/3b24606172648eea459125cb74754afe.jpg, createdBy=6c022216608, createdName=liumin1987, createdTime=Wed Aug 15 11:37:11 CST 2018, time=2018-08-15, status=1, ipAttribution=)]
    2019-07-01 zhaozhouchifen

    #Cell#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2078813, encodeId=767320e8813e4, content=<a href='/topic/show?id=a07d640e05a' target=_blank style='color:#2F92EE;'>#氮代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64070, encryptionId=a07d640e05a, topicName=氮代谢)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca89104, createdName=huperzia, createdTime=Thu Oct 18 10:01:00 CST 2018, time=2018-10-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870810, encodeId=fc9a18e08104b, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Jul 01 06:01:00 CST 2019, time=2019-07-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961080, encodeId=c10f19610806a, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Apr 19 10:01:00 CST 2019, time=2019-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370954, encodeId=966e13e095405, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Fri Aug 17 01:01:00 CST 2018, time=2018-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=338749, encodeId=94ca338e49f9, content=嗯嗯，学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/07/16/3b24606172648eea459125cb74754afe.jpg, createdBy=6c022216608, createdName=liumin1987, createdTime=Wed Aug 15 11:37:11 CST 2018, time=2018-08-15, status=1, ipAttribution=)]
    2019-04-19 维他命

    #CEL#

    0

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    2018-08-17 仁医06

    #致癌#

    0

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    2018-08-15 liumin1987

    嗯嗯，学习了。

    0