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Sci Rep. 2017 Mar 6;7:43710. doi: 10.1038/srep43710.

Data-Driven Discovery of Extravasation Pathway in Circulating Tumor Cells.

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Institute of Bioinformatics, International Technology Park, Whitefield, Bangalore, 560 066, India.
Manipal University, Madhav Nagar, Manipal, 576104, India.
Center for Bioinformatics, Pondicherry University, Puducherry 605 014, India.
Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine NUS Yong Loo Lin School of Medicine, Singapore 117599, Singapore.
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, 560012, India.
YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575018, India.
Comprehensive Cancer Center, Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
CNRS UMR 7057, Matter and Complex Systems, Université Paris Diderot, 10 rue Alice Domon et Léonie Duquet 75013 Paris, France.
Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.


Circulating tumor cells (CTCs) play a crucial role in cancer dissemination and provide a promising source of blood-based markers. Understanding the spectrum of transcriptional profiles of CTCs and their corresponding regulatory mechanisms will allow for a more robust analysis of CTC phenotypes. The current challenge in CTC research is the acquisition of useful clinical information from the multitude of high-throughput studies. To gain a deeper understanding of CTC heterogeneity and identify genes, pathways and processes that are consistently affected across tumors, we mined the literature for gene expression profiles in CTCs. Through in silico analysis and the integration of CTC-specific genes, we found highly significant biological mechanisms and regulatory processes acting in CTCs across various cancers, with a particular enrichment of the leukocyte extravasation pathway. This pathway appears to play a pivotal role in the migration of CTCs to distant metastatic sites. We find that CTCs from multiple cancers express both epithelial and mesenchymal markers in varying amounts, which is suggestive of dynamic and hybrid states along the epithelial-mesenchymal transition (EMT) spectrum. Targeting the specific molecular nodes to monitor disease and therapeutic control of CTCs in real time will likely improve the clinical management of cancer progression and metastases.

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