何为锯齿状结直肠癌?(综述)
创作:祁玉丽 审核:Lexi 2019年12月02日
  • 有相当比例的结直肠癌(CRCs)是通过一种被称为“锯齿状”通路的替代机制形成的;
  • 转录组学方法表明,锯齿状前体病变不仅导致BRAF-突变型/ CpG岛启动子区域高甲基化(CIMP-H)/高微卫星不稳性(MSI-H) CRC,还导致间充质激活和免疫抑制预后不良的CRC亚型;
  • 两种非典型PKCs同时缺失可独立驱动锯齿状CRC,不依赖BRAF和KRAS突变;
  • 基因工程小鼠模型精确概括每一种锯齿状CRCs亚型,为研究其病因、开发新疗法提供思路。
主编推荐语
Lexi
通过传统的腺瘤-癌顺序研究结直肠癌(CRC)起源,对研究控制其发生、发展的分子机制提供了思路。而目前对另一种与之相关的“锯齿状”途径知之甚少,该途径与BRAF突变和微卫星不稳定性相关。最近用来分类人CRC的转录组学方法表明,间充质和/或结缔组织特征与免疫抑制微环境相结合很大程度上决定了CRC的最坏预后。重要的是,这些侵袭性的CRCs具有锯齿状肿瘤的特征,表明通过这一替代途径的肿瘤起源决定了CRC的侵袭性。最新发表于Trends in Cancer的综述回顾了最近关于锯齿状癌变如何导致最差预后的CRC亚型的证据。
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Trends in Cancer [IF:8.884]

Serrated Colorectal Cancer: The Road Less Travelled?

锯齿状结直肠癌:少走的路?

10.1016/j.trecan.2019.09.004

2019-10-28, Review

Abstract & Authors:展开

Abstract:收起
Studies of colorectal cancer (CRC) originating through the conventional adenoma-carcinoma sequence have provided insight into the molecular mechanisms controlling its initiation and progression. Less is known about the alternative ‘serrated’ pathway, which has been associated with BRAF mutation and microsatellite instability. Recent transcriptomics approaches to classify human CRC revealed that mesenchymal and/or desmoplastic features combined with an immunosuppressive microenvironment are key determinants of CRC with the poorest prognosis. Importantly, these aggressive CRCs harbor the characteristics of serrated tumors, suggesting that initiation through this alternative pathway determines how aggressive the CRC becomes. Here, we review recent evidence on how serrated carcinogenesis contributes to the subtype of CRC with the poorest prognosis.

First Authors:
Yuki Nakanishi

Correspondence Authors:
Jorge Moscat

All Authors:
Yuki Nakanishi,Maria T Diaz-Meco,Jorge Moscat

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