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Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma
The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC) are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527782/ https://www.ncbi.nlm.nih.gov/pubmed/26247463 http://dx.doi.org/10.1371/journal.pone.0133562 |
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author | Chen, Dung-Tsa Davis-Yadley, Ashley H. Huang, Po-Yu Husain, Kazim Centeno, Barbara A. Permuth-Wey, Jennifer Pimiento, Jose M. Malafa, Mokenge |
author_facet | Chen, Dung-Tsa Davis-Yadley, Ashley H. Huang, Po-Yu Husain, Kazim Centeno, Barbara A. Permuth-Wey, Jennifer Pimiento, Jose M. Malafa, Mokenge |
author_sort | Chen, Dung-Tsa |
collection | PubMed |
description | The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC) are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment decision-making process. To derive a prognostic gene signature for patients with early stage PDAC, a PDAC cohort from Moffitt Cancer Center (n = 63) was used with overall survival (OS) as the primary endpoint. This was further evaluated using an independent microarray cohort dataset (Stratford et al: n = 102). Technical validation was performed by NanoString platform. A prognostic 15-gene signature was developed and showed a statistically significant association with OS in the Moffitt cohort (hazard ratio [HR] = 3.26; p<0.001) and Stratford et al cohort (HR = 2.07; p = 0.02), and was independent of other prognostic variables. Moreover, integration of the signature with the TNM staging system improved risk prediction (p<0.01 in both cohorts). In addition, NanoString validation showed that the signature was robust with a high degree of reproducibility and the association with OS remained significant in the two cohorts. The gene signature could be a potential prognostic tool to allow risk-adapted stratification of PDAC patients into personalized treatment protocols; possibly improving the currently poor clinical outcomes of these patients. |
format | Online Article Text |
id | pubmed-4527782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45277822015-08-12 Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma Chen, Dung-Tsa Davis-Yadley, Ashley H. Huang, Po-Yu Husain, Kazim Centeno, Barbara A. Permuth-Wey, Jennifer Pimiento, Jose M. Malafa, Mokenge PLoS One Research Article The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC) are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment decision-making process. To derive a prognostic gene signature for patients with early stage PDAC, a PDAC cohort from Moffitt Cancer Center (n = 63) was used with overall survival (OS) as the primary endpoint. This was further evaluated using an independent microarray cohort dataset (Stratford et al: n = 102). Technical validation was performed by NanoString platform. A prognostic 15-gene signature was developed and showed a statistically significant association with OS in the Moffitt cohort (hazard ratio [HR] = 3.26; p<0.001) and Stratford et al cohort (HR = 2.07; p = 0.02), and was independent of other prognostic variables. Moreover, integration of the signature with the TNM staging system improved risk prediction (p<0.01 in both cohorts). In addition, NanoString validation showed that the signature was robust with a high degree of reproducibility and the association with OS remained significant in the two cohorts. The gene signature could be a potential prognostic tool to allow risk-adapted stratification of PDAC patients into personalized treatment protocols; possibly improving the currently poor clinical outcomes of these patients. Public Library of Science 2015-08-06 /pmc/articles/PMC4527782/ /pubmed/26247463 http://dx.doi.org/10.1371/journal.pone.0133562 Text en © 2015 Chen 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chen, Dung-Tsa Davis-Yadley, Ashley H. Huang, Po-Yu Husain, Kazim Centeno, Barbara A. Permuth-Wey, Jennifer Pimiento, Jose M. Malafa, Mokenge Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma |
title | Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma |
title_full | Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma |
title_fullStr | Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma |
title_full_unstemmed | Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma |
title_short | Prognostic Fifteen-Gene Signature for Early Stage Pancreatic Ductal Adenocarcinoma |
title_sort | prognostic fifteen-gene signature for early stage pancreatic ductal adenocarcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527782/ https://www.ncbi.nlm.nih.gov/pubmed/26247463 http://dx.doi.org/10.1371/journal.pone.0133562 |
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