CASTIN: a system for comprehensive analysis of cancer-stromal interactome.
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 .
Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Daisuke
D
Komura
Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Takayuki
T
Isagawa
Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Graduate School of Interdisciplinary Information Studies, The University of Tokyo, Tokyo, Japan.
Kazuki
K
Kishi
Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Graduate School of Information and Science and Technology, The University of Tokyo, Tokyo, Japan.
Ryohei
R
Suzuki
Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Reiko
R
Sato
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Mariko
M
Tanaka
Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Hiroto
H
Katoh
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Shogo
S
Yamamoto
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Kenji
K
Tatsuno
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Masashi
M
Fukayama
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Hiroyuki
H
Aburatani
Department of Genomic Pathology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan. sish.gpat@mri.tmd.ac.jp.
Shumpei
S
Ishikawa
D000818:Animals; D002450:Cell Communication / Q000235:genetics; D045744:Cell Line, Tumor; D019295:Computational Biology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D064593:Heterografts; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D025941:Protein Interaction Mapping / Q000379:methods; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D059467:Transcriptome; D059016:Tumor Microenvironment / Q000235:genetics; D057188:Workflow
Cancer microenvironment; Cancer-stromal interactions; RNA-Seq; Xenograft mouse model