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Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma

Lung adenocarcinoma is often diagnosed at an advanced stage with poor prognosis. Patients with different clinical outcomes may have similar clinico-pathological characteristics. The results of previous studies for biomarkers for lung adenocarcinoma have generally been inconsistent and limited in cli...

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Autores principales: Chang, Ya-Hsuan, Chen, Chung-Ming, Chen, Hsuan-Yu, Yang, Pan-Chyr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455286/
https://www.ncbi.nlm.nih.gov/pubmed/26042604
http://dx.doi.org/10.1038/srep10979
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author Chang, Ya-Hsuan
Chen, Chung-Ming
Chen, Hsuan-Yu
Yang, Pan-Chyr
author_facet Chang, Ya-Hsuan
Chen, Chung-Ming
Chen, Hsuan-Yu
Yang, Pan-Chyr
author_sort Chang, Ya-Hsuan
collection PubMed
description Lung adenocarcinoma is often diagnosed at an advanced stage with poor prognosis. Patients with different clinical outcomes may have similar clinico-pathological characteristics. The results of previous studies for biomarkers for lung adenocarcinoma have generally been inconsistent and limited in clinical application. In this study, we used inverse-variance weighting to combine the hazard ratios for the four datasets and performed pathway analysis to identify prognosis-associated gene signatures. A total of 2,418 genes were found to be significantly associated with overall survival. Of these, a 21-gene signature in the HMGB1/RAGE signalling pathway and a 31-gene signature in the clathrin-coated vesicle cycle pathway were significantly associated with prognosis of lung adenocarcinoma across all four datasets (all p-values < 0.05, log-rank test). We combined the scores for the three pathways to derive a combined pathway-based risk (CPBR) score. Three pathway-based signatures and CPBR score also had more predictive power than single genes. Finally, the CPBR score was validated in two independent cohorts (GSE14814 and GSE13213 in the GEO database) and had significant adjusted hazard ratios 2.72 (p-value < 0.0001) and 1.71 (p-value < 0.0001), respectively. These results could provide a more complete picture of the lung cancer pathogenesis.
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spelling pubmed-44552862015-06-10 Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma Chang, Ya-Hsuan Chen, Chung-Ming Chen, Hsuan-Yu Yang, Pan-Chyr Sci Rep Article Lung adenocarcinoma is often diagnosed at an advanced stage with poor prognosis. Patients with different clinical outcomes may have similar clinico-pathological characteristics. The results of previous studies for biomarkers for lung adenocarcinoma have generally been inconsistent and limited in clinical application. In this study, we used inverse-variance weighting to combine the hazard ratios for the four datasets and performed pathway analysis to identify prognosis-associated gene signatures. A total of 2,418 genes were found to be significantly associated with overall survival. Of these, a 21-gene signature in the HMGB1/RAGE signalling pathway and a 31-gene signature in the clathrin-coated vesicle cycle pathway were significantly associated with prognosis of lung adenocarcinoma across all four datasets (all p-values < 0.05, log-rank test). We combined the scores for the three pathways to derive a combined pathway-based risk (CPBR) score. Three pathway-based signatures and CPBR score also had more predictive power than single genes. Finally, the CPBR score was validated in two independent cohorts (GSE14814 and GSE13213 in the GEO database) and had significant adjusted hazard ratios 2.72 (p-value < 0.0001) and 1.71 (p-value < 0.0001), respectively. These results could provide a more complete picture of the lung cancer pathogenesis. Nature Publishing Group 2015-06-04 /pmc/articles/PMC4455286/ /pubmed/26042604 http://dx.doi.org/10.1038/srep10979 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chang, Ya-Hsuan
Chen, Chung-Ming
Chen, Hsuan-Yu
Yang, Pan-Chyr
Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma
title Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma
title_full Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma
title_fullStr Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma
title_full_unstemmed Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma
title_short Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma
title_sort pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455286/
https://www.ncbi.nlm.nih.gov/pubmed/26042604
http://dx.doi.org/10.1038/srep10979
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