CASTIN: a system for comprehensive analysis of cancer-stromal interactome. (December 2016)

• Record Type: Journal Article
• Authors: Komura, Daisuke; Isagawa, Takayuki; Kishi, Kazuki; Suzuki, Ryohei; Sato, Reiko; Tanaka, Mariko; Katoh, Hiroto; Yamamoto, Shogo; Tatsuno, Kenji; Fukayama, Masashi; Aburatani, Hiroyuki; Ishikawa, Shumpei
• Is Part Of: BMC genomics. Volume 17:Number 1(2016)
• Page Start: 1
• Page End: 18
• Publication Date: 2016-12
• Subjects: Cancer microenvironment -- Cancer-stromal interactions -- Xenograft mouse model -- RNA-Seq; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-016-3207-z
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background 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. Results 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. Conclusions 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 .