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Sci Rep:透明细胞肾细胞癌肿瘤样本中,评估的肿瘤纯度对基于药物重定位的基因表达影响研究

2019-03-09 AlexYang MedSci原创

最近,有研究人员为了发现之前用于治疗其他疾病药物中,能够治疗透明细胞肾细胞癌(ccRCC)的药物,他们之前搜寻了预期能够将来自癌症基因组计划中的500+ccRCC样本的基因表达水平回归到健康肾组织样本基因表达水平的药物。他们研究中的混样池RNA-seq数据的内在限制为肿瘤样本包含了各种各样的癌细胞和非癌细胞,影响了差异基因表达分析。在新的研究中,研究人员通过研究与肿瘤纯度的相关性,调查了是否候选药

最近,有研究人员为了发现之前用于治疗其他疾病药物中,能够治疗透明细胞肾细胞癌(ccRCC)的药物,他们之前搜寻了预期能够将来自癌症基因组计划中的500+ccRCC样本的基因表达水平回归到健康肾组织样本基因表达水平的药物。他们研究中的混样池RNA-seq数据的内在限制为肿瘤样本包含了各种各样的癌细胞和非癌细胞,影响了差异基因表达分析。

在新的研究中,研究人员通过研究与肿瘤纯度的相关性,调查了是否候选药物重新定位能够靶向在ccRCC细胞中表达异常的基因。当所有的样本在一起分析的时候,已经鉴定过的药物重定位能够减少多于80%的评估肿瘤纯度。因为ccRCC是一种高度血管化的肿瘤,并归因于VHL功能的丧失和缺氧诱导因子(HIF)的激活,研究人员通过观察HIF途径的激活来对样本进行分层。之后,研究人员发现,评估的肿瘤纯度与药物重定位相关性在HIF激活的样本中消失。该结果表明了鉴定过的候选药物重定位能够特异性的靶向HIF激活的ccRCC肿瘤细胞的表达基因,而不是部分肿瘤微环境中其他细胞类型表达的基因。

原始出处:

Karel K. M. Koudijs, Anton G. T. Terwisscha van Scheltinga, Stefan BÖhringer et al. The impact of estimated tumour purity on gene expression-based drug repositioning of Clear Cell Renal Cell Carcinoma samples. Sci Rep. 21 Feb 2019.

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    2019-04-25 zhzhxiang
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    2019-03-13 衣带渐宽

    学习

    0

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