CASTIN: a system for comprehensive analysis of cancer-stromal interactome.

CASTIN: a system for comprehensive analysis of cancer-stromal interactome.
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DOI:
10.1186/s12864-016-3207-z
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发表时间:
2016-11-09
期刊:
影响因子:
4.4
通讯作者:
Ishikawa S
Ishikawa S
中科院分区:
生物学2区
文献类型:
--
作者:
Komura D;Isagawa T;Kishi K;Suzuki R;Sato R;Tanaka M;Katoh H;Yamamoto S;Tatsuno K;Fukayama M;Aburatani H;Ishikawa S

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肿瘤微环境在肿瘤的发生、发展中起着重要的作用,肿瘤-间质相互作用已被认为是肿瘤治疗的重要靶点。然而,由于缺乏定量方法来分析整个癌症-间质相互作用组,鉴定相关的和可药物化的癌症-间质相互作用具有挑战性。我们提出了CASTIN(癌症-基质相互作用组分析),这是一种使用癌症异种移植模型从RNA-Seq数据评估癌症-基质相互作用组的新框架。CASTIN从Curated Protein Interaction Database中提取配体-受体相互作用数据,将肿瘤和间质的基因表达谱归纳为三个评价指标。这些指标提供了相互作用组的定量评估和全面可视化,从而能够识别关键的癌症-微环境相互作用,这将是潜在的药物靶点。我们将CASTIN应用于胰腺导管腺癌的数据集,并成功地在癌症-基质关系方面表征了个体癌症,并确定了众所周知和较少表征的药物相互作用。CASTIN提供了癌症-基质相互作用组的全面视图,并有助于识别可能作为癌症微环境中潜在药物靶点的关键相互作用。CASTIN可在http://github.com/tmd-gpat/CASTIN上获得。本文的在线版本(doi:10.1186/s12864-016-3207-z)包含补充材料,可供授权用户使用。
Cancer microenvironment plays a vital role in cancer development and progression, and cancer-stromal interactions have been recognized as important targets for cancer therapy. However, identifying relevant and druggable cancer-stromal interactions is challenging due to the lack of quantitative methods to analyze whole cancer-stromal interactome. We present CASTIN (CAncer-STromal INteractome analysis), a novel framework for the evaluation of cancer-stromal interactome from RNA-Seq data using cancer xenograft models. For each ligand-receptor interaction which is derived from curated protein-protein interaction database, CASTIN summarizes gene expression profiles of cancer and stroma into three evaluation indices. These indices provide quantitative evaluation and comprehensive visualization of interactome, and thus enable to identify critical cancer-microenvironment interactions, which would be potential drug targets. We applied CASTIN to the dataset of pancreas ductal adenocarcinoma, and successfully characterized the individual cancer in terms of cancer-stromal relationships, and identified both well-known and less-characterized druggable interactions. CASTIN provides comprehensive view of cancer-stromal interactome and is useful to identify critical interactions which may serve as potential drug targets in cancer-microenvironment. CASTIN is available at: http://github.com/tmd-gpat/CASTIN. The online version of this article (doi:10.1186/s12864-016-3207-z) contains supplementary material, which is available to authorized users.
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