在近9000名患者样本中进行全癌症增强表达分析
Han Chen1, Chunyan Li2, Xinxin Peng1
1Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cell
|April 7, 2018
概括
科学家在成千上万的癌症样本中发现了活性增强剂, 增强剂活动与癌症复杂性有关, 不仅仅是突变, 也可以调节PD-L1等关键基因, 提供新的治疗点.
科学领域:
- 基因组学
- 癌症生物学
- 表观遗传学
背景情况:
- 增强剂是一种重要的非编码调节性DNA元素,越来越多地被认为对癌症的发展起作用.
- 了解不同癌症类型的增强剂活性对于破译癌症生物学和确定治疗点至关重要.
研究的目的:
- 通过使用癌症基因组图谱 (TCGA) RNA-seq数据,在33种癌症类型中检测和描述表达增强剂.
- 调查增强剂活性与基因组特征的关联,如体积和突变负载.
- 通过计算推断因果增强剂-基因相互作用,并确定临床可操作基因的增强剂.
主要方法:
- 在TCGA的8928个瘤样本中对表达增强剂进行全基因组分析.
- 对瘤中的增强剂活性与匹配的正常组织进行比较分析.
- 整合eQTL,mRNA联合表达和Hi-C数据以推断增强剂-基因相互作用.
- 已识别的增强剂的实验验证,包括PD-L1基因附近的增强剂.
主要成果:
- 与正常组织相比,在大多数癌症类型中观察到全局增强剂激活.
- 全球增强剂活性与形质相关,但不与突变负载相关,这表明基于染色体状态的相互作用.
- 一种计算方法成功推断了因果增强剂-基因相互作用,确定了临床相关基因的增强剂.
- 一种大约在PD- L1下游的增强剂是免疫治疗的关键点,并经过实验验证实.
结论:
- 这项研究提供了广泛的瘤环境中增强剂活性的全面观点.
- 增强剂活性是癌症发展的一个重要因素,可能受到染色质状态和动体积的影响.
- 确定的增强剂-基因相互作用,特别是对于PD-L1等点,突显了增强剂在癌症治疗中的临床含义.
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