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JAMA Neurology:脑脊液下一代基因组测序技术在肿瘤检测中的应用

2021-12-02 Naomi MedSci原创

该病例对照研究表明,CSF mNGS的样本体积要求低,不需要保持细胞的完整性,而且最初是用来诊断神经系统感染的,在脑脊液细胞学和/或流式细胞仪检测结果为阴性的患者中,也可检测出CNS恶性肿瘤的遗传证据

      识别脑膜脑炎的病因是一个挑战,大约有一半的病例没有得到诊断。主要的诊断考虑因素包括隐匿性感染、自身免疫性疾病和各种恶性肿瘤,其中一些可能表现为软脑膜癌。然而,众所周知,即使在多次大容量脑脊液(CSF)检查之后,恶性疾病也很难诊断。这一困难可能与脑脊液的稀少细胞性质有关,包括少量的恶性细胞,或者需要在细胞溶解之前保存细胞的形态结构。由于中枢神经系统(CNS)恶性肿瘤、感染和炎性综合征可能在临床和放射学上重叠,因此一项可以检测到多种难以诊断的疾病的单一检查将具有潜在的临床应用价值。

      已有研究报道使用元基因组下一代测序技术(MNGS)检测脑脊液中的多种病原体。元基因组下一代测序从脑脊液样本中的所有遗传物质中产生序列,并且脑脊液中的大部分序列是人类的。以前的研究已经在CSF中发现了CNS肿瘤DNA。研究假设CSF mNGS人类数据可以被重新利用来检测非整倍体作为CNS恶性肿瘤的特异性标志物。非整倍体和其他大拷贝数变异(CNV)在原发性和转移性中枢神经系统肿瘤中普遍存在,大约90%的恶性肿瘤染色体数目异常(即异倍体)。为了确定CSF mNGS能否在难于诊断的中枢神经系统恶性肿瘤中识别非整倍体,研究者采用无创性产前检查的覆盖深度方法进行了两项病例对照研究,探讨脑脊液亚基因组下一代测序(MNGS)能否在难于诊断的中枢神经系统恶性肿瘤中鉴别出恶性肿瘤的标志之一——异倍体。

       加州大学旧金山分校(UCSF)进行了两项病例对照研究。第一项研究使用了2017年7月1日-2019年12月31日在加州大学旧金山分校临床实验室收集的CSF样本,并评估了CNS恶性肿瘤患者(阳性对照)和非中枢神经系统恶性肿瘤患者(阴性对照)标本的测试性能。并与脑脊液细胞学检测和/或流式细胞仪检测结果进行比较。第二项研究评估了在2014年4月1日-2019年7月31日期间参加正在进行的前瞻性研究的患者,这些患者的陈述提示神经炎性疾病,但最终被诊断为中枢神经系统恶性肿瘤。对其肿瘤可以在没有额外侵入性检测的情况下更早被发现的个体的案例进行了讨论。

      主要观察指标为脑脊液mNGS检测非整倍体的敏感性和特异性。次级亚组分析包括比较脑脊液和肿瘤组织的染色体异常,以及识别与测试表现相关的神经影像特征。

  • 在这两项研究中,130名参与者被纳入(中位数[四分位数范围]年龄,57.5[43.3-68.0]岁;72名男性[55.4%])。
  • 这项测试性能研究使用了来自47名中枢神经系统恶性肿瘤患者和56名其他神经系统疾病患者的125份实验室残留脑脊液样本。
  • 神经炎性疾病研究招募了12名患者和17名匹配的对照组参与者。
  • 脑脊液mNGS检测的敏感性为75%(95%CI,63%~85%),特异性为100%(95%CI,96%~100%)。
  • 在非诊断性细胞学检测和/或流式细胞术检测中,64%(95%CI,41%~83%)的患者检测到非整倍体;在神经炎性疾病研究中,55%(95%CI,23%~83%)的患者最终诊断为中枢神经系统恶性肿瘤。
  • 在检测到非整倍体的患者中,38例(90.5%)有多拷贝数变异,肿瘤比例从31%到49%不等。

      这项病例对照研究表明,CSF mNGS的样本体积要求低,不需要保持细胞的完整性,而且最初是用来诊断神经系统感染的,在脑脊液细胞学和/或流式细胞仪检测结果为阴性的患者中,也可以检测出CNS恶性肿瘤的遗传证据,假阳性的风险很低。

文献来源:Gu W, Rauschecker AM, Hsu E, et al. Detection of Neoplasms by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid [published online ahead of print, 2021 Sep 13]. JAMA Neurol. 2021;e213088. doi:10.1001/jamaneurol.2021.3088

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    学习

    0

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    2021-12-03 ms9000001414426655

    学习了

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2001622, encodeId=40ab2001622dd, content=<a href='/topic/show?id=d5df12695e6' target=_blank style='color:#2F92EE;'>#Neurol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12695, encryptionId=d5df12695e6, topicName=Neurol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Mon Aug 01 04:38:04 CST 2022, time=2022-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028443, encodeId=7d972028443f1, content=<a href='/topic/show?id=a558829e98a' target=_blank style='color:#2F92EE;'>#肿瘤检测#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82979, encryptionId=a558829e98a, topicName=肿瘤检测)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2bcd469, createdName=fengting3, createdTime=Fri Feb 04 18:38:04 CST 2022, time=2022-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1220718, encodeId=ba551220e1834, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d416160714, createdName=ms8000000185867059, createdTime=Wed May 18 19:24:04 CST 2022, time=2022-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1076598, encodeId=475610e6598b8, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c70d5596086, createdName=ms9000001414426655, createdTime=Fri Dec 03 16:58:42 CST 2021, time=2021-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1076201, encodeId=c9cd10e620111, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Dec 02 12:47:46 CST 2021, time=2021-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1076200, encodeId=04e410e620078, content=血液肿瘤中脑脊液流式细胞学检查用于评估是否有中枢累计, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLjVAQdeYaIiaUFtNz9up3fh5JnRLu08bx3Xbz9XfTdoUiby8zX2TjyBfupJ3kbksmwEI6lR7WBLWsg/132, createdBy=9fae5199915, createdName=wlonglai, createdTime=Thu Dec 02 12:47:19 CST 2021, time=2021-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1438194, encodeId=5ff91438194d3, content=<a href='/topic/show?id=48f9418406e' target=_blank style='color:#2F92EE;'>#基因组测序#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41840, encryptionId=48f9418406e, topicName=基因组测序)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue Nov 16 14:38:04 CST 2021, time=2021-11-16, status=1, ipAttribution=)]
    2021-12-02 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2021-12-02 wlonglai

    血液肿瘤中脑脊液流式细胞学检查用于评估是否有中枢累计

    0

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