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Data-Driven Discovery of Extravasation Pathway in Circulating Tumor Cells

Yadavalli, S
Jayaram, S
Manda, S.S
Madugundu, A.K
Nayakanti, D.S
Tan, T.Z
Bhat, R
Rangarajan, A
Chatterjee, A
Gowda, H
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Abstract
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. © 2017 The Author(s).
Keywords
transcriptome, tumor marker, biology, data mining, epithelial mesenchymal transition, gene expression profiling, gene expression regulation, genetic database, genetics, human, leukocyte, metabolism, molecular genetics, neoplasm, pathology, procedures, signal transduction, tumor cell line, tumor embolism, Biomarkers, Tumor, Cell Line, Tumor, Computational Biology, Data Mining, Databases, Genetic, Epithelial-Mesenchymal Transition, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Leukocytes, Molecular Sequence Annotation, Neoplasms, Neoplastic Cells, Circulating, Signal Transduction, Transcriptome
Source Title
Scientific Reports
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BIOCHEMISTRY
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Date
2017
DOI
10.1038/srep43710
Type
Article
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