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Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity

BACKGROUND: Squamous cell lung cancer (SqCC) is the second most common type of lung cancer in the United States. Previous studies have used gene-expression data to classify SqCC samples into four subtypes, including the primitive, classical, secretory and basal subtypes. These subtypes have differen...

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Autores principales: Wu, D, Pang, Y, Wilkerson, M D, Wang, D, Hammerman, P S, Liu, J S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776976/
https://www.ncbi.nlm.nih.gov/pubmed/24002593
http://dx.doi.org/10.1038/bjc.2013.452
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author Wu, D
Pang, Y
Wilkerson, M D
Wang, D
Hammerman, P S
Liu, J S
author_facet Wu, D
Pang, Y
Wilkerson, M D
Wang, D
Hammerman, P S
Liu, J S
author_sort Wu, D
collection PubMed
description BACKGROUND: Squamous cell lung cancer (SqCC) is the second most common type of lung cancer in the United States. Previous studies have used gene-expression data to classify SqCC samples into four subtypes, including the primitive, classical, secretory and basal subtypes. These subtypes have different survival outcomes, although it is unknown whether these molecular subtypes predict response to therapy. METHODS: Here, we analysed RNAseq data of 178 SqCC tumour samples and characterised the features of the different SqCC subtypes to define signature genes and pathway alterations specific to each subtype. Further, we compared the gene-expression features of each molecular subtype to specific time points in models of airway development. We also classified SqCC-derived cell lines and their reported therapeutic vulnerabilities. RESULTS: We found that the primitive subtype may come from a later stage of differentiation, whereas the basal subtype may be from an early time. Most SqCC cell lines responded to one of five anticancer drugs (Panobinostat, 17-AAG, Irinotecan, Topotecan and Paclitaxel), whereas the basal-type cell line EBC-1 was sensitive to three other drugs (PF2341066, AZD6244 and PD-0325901). CONCLUSION: Compared with the other three subtypes of cell lines, the secretory-type cell lines were significantly less sensitive to the five most effective drugs, possibly because of their low proliferation activity. We provide a bioinformatics framework to explore drug repurposing for cancer subtypes based on the available genomic profiles of tumour samples, normal cell types, cancer cell lines and data of drug sensitivity in cell lines.
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spelling pubmed-37769762014-09-17 Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity Wu, D Pang, Y Wilkerson, M D Wang, D Hammerman, P S Liu, J S Br J Cancer Molecular Diagnostics BACKGROUND: Squamous cell lung cancer (SqCC) is the second most common type of lung cancer in the United States. Previous studies have used gene-expression data to classify SqCC samples into four subtypes, including the primitive, classical, secretory and basal subtypes. These subtypes have different survival outcomes, although it is unknown whether these molecular subtypes predict response to therapy. METHODS: Here, we analysed RNAseq data of 178 SqCC tumour samples and characterised the features of the different SqCC subtypes to define signature genes and pathway alterations specific to each subtype. Further, we compared the gene-expression features of each molecular subtype to specific time points in models of airway development. We also classified SqCC-derived cell lines and their reported therapeutic vulnerabilities. RESULTS: We found that the primitive subtype may come from a later stage of differentiation, whereas the basal subtype may be from an early time. Most SqCC cell lines responded to one of five anticancer drugs (Panobinostat, 17-AAG, Irinotecan, Topotecan and Paclitaxel), whereas the basal-type cell line EBC-1 was sensitive to three other drugs (PF2341066, AZD6244 and PD-0325901). CONCLUSION: Compared with the other three subtypes of cell lines, the secretory-type cell lines were significantly less sensitive to the five most effective drugs, possibly because of their low proliferation activity. We provide a bioinformatics framework to explore drug repurposing for cancer subtypes based on the available genomic profiles of tumour samples, normal cell types, cancer cell lines and data of drug sensitivity in cell lines. Nature Publishing Group 2013-09-17 2013-09-03 /pmc/articles/PMC3776976/ /pubmed/24002593 http://dx.doi.org/10.1038/bjc.2013.452 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Molecular Diagnostics
Wu, D
Pang, Y
Wilkerson, M D
Wang, D
Hammerman, P S
Liu, J S
Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity
title Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity
title_full Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity
title_fullStr Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity
title_full_unstemmed Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity
title_short Gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity
title_sort gene-expression data integration to squamous cell lung cancer subtypes reveals drug sensitivity
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776976/
https://www.ncbi.nlm.nih.gov/pubmed/24002593
http://dx.doi.org/10.1038/bjc.2013.452
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