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Mol Cancer:新型生物标志物SNORD33可预测三阴性乳腺癌对铂类化疗敏感性

2022-03-14 MedSci原创 MedSci原创

三阴性乳腺癌是具有高侵袭性及转移性的乳腺癌亚型,患者复发比例高,总体生存率低,是临床治疗的难点。铂类药物是治疗三阴性乳腺癌的有效药物,然而,耐药仍不可避免。既往包括BRCA突变在内的标志物对铂类疗效的

三阴性乳腺癌是具有高侵袭性及转移性的乳腺癌亚型,患者复发比例高,总体生存率低,是临床治疗的难点。铂类药物是治疗三阴性乳腺癌的有效药物,然而,耐药仍不可避免。既往包括BRCA突变在内的标志物对铂类疗效的预测效力在不同研究中的结果并不一致。复旦大学基础医学院陈舌研究员、附属肿瘤医院王碧芸教授及公共卫生学院付朝伟教授团队合作发现血浆小核仁RNA SNORD33对于三阴性乳腺癌患者铂类药物敏感性的预测作用,并揭示甲基化结合蛋白MeCP2参与SNORD33调控的铂类耐药分子机制。相关研究成果《A plasma SNORD33 signature predicts platinum benefit in metastatic triple-negative breast cancer patients》近日在线发表于Molecular Cancer期刊上。 

       snoRNA是一类小分子非编码RNA,参与核糖体的生物合成以及剪接体的剪切组装,且在血浆中含量丰富,可作为液体活检的潜在生物标志物。研究团队发现,顺铂耐药的三阴性乳腺癌SNORD33表达显著降低,下调SNORD33促进顺铂耐药。进而,在既往一线接受含铂和非铂方案治疗的转移性三阴性乳腺癌患者的血浆样本中发现,血浆SNORD33低水平的患者无进展生存时间(PFS)和总生存时间(OS)显著缩短,血浆SNORD33特异性预测铂类疗效,是使用含铂方案治疗患者PFS的独立预测因子。研究基于肝转移状态、转移灶数目的临床特征及血浆SNORD33水平绘制了预测含铂方案PFS时间的列线阵图,用于预测患者铂类药物治疗不同时间临床缓解可能性,以供临床医生/患者参考,选择治疗方案。

       研究发现SNORD33可阻碍甲基化结合蛋白MeCP2与其靶基因的结合,从而释放MeCP2的转录抑制活性,促进凋亡相关基因表达,增加三阴性乳腺癌细胞对铂类的敏感性。

       本研究结果提供了高准确性、检测便利、非侵入性的新的分子标记物和治疗的特异性靶标。采集0.2毫升血浆检测SNORD33水平,结合临床特征,即可实现预测转移性三阴性乳腺癌铂类药物疗效,为肿瘤患者带来更多获益。在新辅助化疗及其它癌种患者含铂治疗方案中的应用,相关验证工作正在有序开展中。

文章信息及链接:Biyun Wang1#, Yannan Zhao1,2#, Yi Li1,2#, Yingying Xu2#, Yun Chen3, Qiuyu Jiang2,4, Dingjin Yao2, Li Zhang2, Xichun Hu1*, Chaowei Fu3*, Si Zhang2*, She Chen2*. A plasma SNORD33 signature predicts platinum benefit in metastatic triple-negative breast cancer patients.

https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-022-01504-0

 文章作者及基金支持:王碧芸教授,赵燕南医师,李懿医师,徐莺莺副教授为并列第一作者,陈舌研究员,张思教授,付朝伟教授,胡夕春教授为联合通讯作者。该研究受国家自然科学基金支持。

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  4. 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  5. 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target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458825, encodeId=caae1458825e2, content=<a href='/topic/show?id=3ef91982030' target=_blank style='color:#2F92EE;'>#三阴性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19820, encryptionId=3ef91982030, topicName=三阴性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5666112721, createdName=xlysu, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1561129, encodeId=65281561129fd, content=<a href='/topic/show?id=3c746936567' target=_blank style='color:#2F92EE;'>#生物标志#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69365, encryptionId=3c746936567, topicName=生物标志)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63db15173977, createdName=zhu_jun9842, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1567138, encodeId=705f156e138ad, content=<a href='/topic/show?id=3c746936567' target=_blank style='color:#2F92EE;'>#生物标志#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69365, encryptionId=3c746936567, topicName=生物标志)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63db15173977, createdName=zhu_jun9842, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568631, encodeId=f29e1568631f5, content=<a href='/topic/show?id=139f9658680' target=_blank style='color:#2F92EE;'>#铂类#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96586, encryptionId=139f9658680, topicName=铂类)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8eed15401054, createdName=fengxx, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=)]
    2022-08-13 huagfeg
  6. 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  7. [GetPortalCommentsPageByObjectIdResponse(id=2028883, encodeId=2165202888385, content=<a href='/topic/show?id=b2bd33559be' target=_blank style='color:#2F92EE;'>#化疗敏感#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33559, encryptionId=b2bd33559be, topicName=化疗敏感)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/6238544484D1FE65CCBBD849EAEE67C2/100, createdBy=47102500004, createdName=ms9651749636653578, createdTime=Mon Sep 12 13:03:58 CST 2022, time=2022-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048108, encodeId=936020481085c, content=<a href='/topic/show?id=12e49e53102' target=_blank style='color:#2F92EE;'>#阴性乳腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97531, encryptionId=12e49e53102, 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target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=111, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458825, encodeId=caae1458825e2, content=<a href='/topic/show?id=3ef91982030' target=_blank style='color:#2F92EE;'>#三阴性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19820, encryptionId=3ef91982030, topicName=三阴性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a5666112721, createdName=xlysu, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1561129, encodeId=65281561129fd, content=<a href='/topic/show?id=3c746936567' target=_blank style='color:#2F92EE;'>#生物标志#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69365, encryptionId=3c746936567, topicName=生物标志)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63db15173977, createdName=zhu_jun9842, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1567138, encodeId=705f156e138ad, content=<a href='/topic/show?id=3c746936567' target=_blank style='color:#2F92EE;'>#生物标志#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69365, encryptionId=3c746936567, topicName=生物标志)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63db15173977, createdName=zhu_jun9842, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568631, encodeId=f29e1568631f5, content=<a href='/topic/show?id=139f9658680' target=_blank style='color:#2F92EE;'>#铂类#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96586, encryptionId=139f9658680, topicName=铂类)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8eed15401054, createdName=fengxx, createdTime=Wed Mar 16 12:03:58 CST 2022, time=2022-03-16, status=1, ipAttribution=)]
    2022-03-16 xlysu
  8. 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  9. 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  10. 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    2022-03-16 fengxx

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