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Cancer cell redirection biomarker discovery using a mutual information approach.
Roche, Kimberly; Feltus, F Alex; Park, Jang Pyo; Coissieux, Marie-May; Chang, Chenyan; Chan, Vera B S; Bentires-Alj, Mohamed; Booth, Brian W.
Afiliação
  • Roche K; Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America.
  • Feltus FA; Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America.
  • Park JP; Institute for Biological Interfaces of Engineering, Clemson University, Clemson, South Carolina, United States of America.
  • Coissieux MM; Department of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
  • Chang C; Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
  • Chan VBS; Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, United States of America.
  • Bentires-Alj M; Department of Biological Sciences, Clemson University, Clemson, South Carolina, United States of America.
  • Booth BW; Department of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland.
PLoS One ; 12(6): e0179265, 2017.
Article em En | MEDLINE | ID: mdl-28594912
Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection biomarkers that cause the redirected state to shift toward the normal expression pattern, we used mutual information relationships between normal, redirected, and tumor cell groups. Mutual information relationship analysis reduced a dataset of over 35,000 gene expression measurements spread over 13,000 curated gene sets to a set of 20 significant molecular signatures totaling 906 unique loci. Several of these molecular signatures are hallmark drivers of the tumor state. Using differential expression as a guide, we further refined the gene set to 120 core redirection biomarker genes. The expression levels of these core biomarkers are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Neoplasias Mamárias Animais / Modelos Biológicos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Neoplasias Mamárias Animais / Modelos Biológicos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos