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Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers
In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112874/ https://www.ncbi.nlm.nih.gov/pubmed/27846280 http://dx.doi.org/10.1371/journal.pone.0165856 |
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author | Kim, Doris Choi, YounJeong Ireland, James Foreman, Oded Tam, Rachel N. Patel, Rajesh Schleifman, Erica B. Motlhabi, Maipelo French, Dorothy Wong, Cheryl V. Peters, Eric Molinero, Luciana Raja, Rajiv Amler, Lukas C. Hampton, Garret M. Lackner, Mark R. Kabbarah, Omar |
author_facet | Kim, Doris Choi, YounJeong Ireland, James Foreman, Oded Tam, Rachel N. Patel, Rajesh Schleifman, Erica B. Motlhabi, Maipelo French, Dorothy Wong, Cheryl V. Peters, Eric Molinero, Luciana Raja, Rajiv Amler, Lukas C. Hampton, Garret M. Lackner, Mark R. Kabbarah, Omar |
author_sort | Kim, Doris |
collection | PubMed |
description | In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes. On a technical level, our bladder cancer panel yielded robust and reproducible results when analyzing formalin-fixed, paraffin-embedded (FFPE) tissues. We applied our panel in the analysis of a novel set of 204 FFPE samples that included non-muscle invasive bladder cancers (NMIBCs), muscle invasive disease (MIBCs), and bladder cancer metastases (METs). We found NMIBCs to be mostly luminal-like, MIBCs to include both luminal- and basal-like types, and METs to be predominantly of a basal-like transcriptional profile. Mutational analysis confirmed the expected enrichment of FGFR3 mutations in luminal samples, and, consistently, FGFR3 IHC showed high protein expression levels of the receptor in these tumors. Our bladder cancer panel enables basal/luminal characterization of FFPE tissues and with further development could be used for stratification of bladder cancer samples in the clinic. |
format | Online Article Text |
id | pubmed-5112874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51128742016-12-08 Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers Kim, Doris Choi, YounJeong Ireland, James Foreman, Oded Tam, Rachel N. Patel, Rajesh Schleifman, Erica B. Motlhabi, Maipelo French, Dorothy Wong, Cheryl V. Peters, Eric Molinero, Luciana Raja, Rajiv Amler, Lukas C. Hampton, Garret M. Lackner, Mark R. Kabbarah, Omar PLoS One Research Article In the age of personalized medicine stratifying tumors into molecularly defined subtypes associated with distinctive clinical behaviors and predictable responses to therapies holds tremendous value. Towards this end, we developed a custom microfluidics-based bladder cancer gene expression panel for characterization of archival clinical samples. In silico analysis indicated that the content of our panel was capable of accurately segregating bladder cancers from several public datasets into the clinically relevant basal and luminal subtypes. On a technical level, our bladder cancer panel yielded robust and reproducible results when analyzing formalin-fixed, paraffin-embedded (FFPE) tissues. We applied our panel in the analysis of a novel set of 204 FFPE samples that included non-muscle invasive bladder cancers (NMIBCs), muscle invasive disease (MIBCs), and bladder cancer metastases (METs). We found NMIBCs to be mostly luminal-like, MIBCs to include both luminal- and basal-like types, and METs to be predominantly of a basal-like transcriptional profile. Mutational analysis confirmed the expected enrichment of FGFR3 mutations in luminal samples, and, consistently, FGFR3 IHC showed high protein expression levels of the receptor in these tumors. Our bladder cancer panel enables basal/luminal characterization of FFPE tissues and with further development could be used for stratification of bladder cancer samples in the clinic. Public Library of Science 2016-11-15 /pmc/articles/PMC5112874/ /pubmed/27846280 http://dx.doi.org/10.1371/journal.pone.0165856 Text en © 2016 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kim, Doris Choi, YounJeong Ireland, James Foreman, Oded Tam, Rachel N. Patel, Rajesh Schleifman, Erica B. Motlhabi, Maipelo French, Dorothy Wong, Cheryl V. Peters, Eric Molinero, Luciana Raja, Rajiv Amler, Lukas C. Hampton, Garret M. Lackner, Mark R. Kabbarah, Omar Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers |
title | Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers |
title_full | Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers |
title_fullStr | Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers |
title_full_unstemmed | Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers |
title_short | Development and Application of a Microfluidics-Based Panel in the Basal/Luminal Transcriptional Characterization of Archival Bladder Cancers |
title_sort | development and application of a microfluidics-based panel in the basal/luminal transcriptional characterization of archival bladder cancers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112874/ https://www.ncbi.nlm.nih.gov/pubmed/27846280 http://dx.doi.org/10.1371/journal.pone.0165856 |
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