Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target
Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease. In an at...
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| Veröffentlicht in: | PloS one 2008-03, Vol.3 (3), p.e0001722-e0001722 |
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| creator | Gallegos Ruiz, Mariëlle I Floor, Karijn Roepman, Paul Rodriguez, José A Meijer, Gerrit A Mooi, Wolter J Jassem, Ewa Niklinski, Jacek Muley, Thomas van Zandwijk, Nico Smit, Egbert F Beebe, Kristin Neckers, Len Ylstra, Bauke Giaccone, Giuseppe |
| description | Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease.
In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines.
We suggest that targeting HSP90 will have clinical impact for NSCLC patients. |
| doi_str_mv | 10.1371/journal.pone.0001722 |
| format | Article |
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In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines.
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In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines.
We suggest that targeting HSP90 will have clinical impact for NSCLC patients.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - secondary</subject><subject>Algorithms</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Carcinoma, Large Cell - genetics</subject><subject>Carcinoma, Large Cell - metabolism</subject><subject>Carcinoma, Large Cell - secondary</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - secondary</subject><subject>Cell cycle</subject><subject>Chromosome Aberrations</subject><subject>Chromosome deletion</subject><subject>Chromosomes, Human, Pair 14 - genetics</subject><subject>Clonal deletion</subject><subject>Comparative analysis</subject><subject>Copy number</subject><subject>Cytogenetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA microarrays</subject><subject>Drug dosages</subject><subject>Endocrinology</subject><subject>Epidermal growth factor</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene deletion</subject><subject>Gene Dosage</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetics and Genomics</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health aspects</subject><subject>Heat shock proteins</subject><subject>HSP90 Heat-Shock Proteins - genetics</subject><subject>Hsp90 protein</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Immunology</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung 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Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gallegos Ruiz, Mariëlle I</au><au>Floor, Karijn</au><au>Roepman, Paul</au><au>Rodriguez, José A</au><au>Meijer, Gerrit A</au><au>Mooi, Wolter J</au><au>Jassem, Ewa</au><au>Niklinski, Jacek</au><au>Muley, Thomas</au><au>van Zandwijk, Nico</au><au>Smit, Egbert F</au><au>Beebe, Kristin</au><au>Neckers, Len</au><au>Ylstra, Bauke</au><au>Giaccone, Giuseppe</au><au>Plass, Christoph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2008-03-05</date><risdate>2008</risdate><volume>3</volume><issue>3</issue><spage>e0001722</spage><epage>e0001722</epage><pages>e0001722-e0001722</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease.
In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines.
We suggest that targeting HSP90 will have clinical impact for NSCLC patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18320023</pmid><doi>10.1371/journal.pone.0001722</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2008-03, Vol.3 (3), p.e0001722-e0001722 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312436794 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenocarcinoma - genetics Adenocarcinoma - metabolism Adenocarcinoma - secondary Algorithms Cancer Cancer genetics Carcinoma, Large Cell - genetics Carcinoma, Large Cell - metabolism Carcinoma, Large Cell - secondary Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - secondary Cell cycle Chromosome Aberrations Chromosome deletion Chromosomes, Human, Pair 14 - genetics Clonal deletion Comparative analysis Copy number Cytogenetics Deoxyribonucleic acid DNA DNA microarrays Drug dosages Endocrinology Epidermal growth factor Female Follow-Up Studies Gene deletion Gene Dosage Gene expression Gene Expression Regulation, Neoplastic Genes Genetics and Genomics Genome, Human Genomes Genomics Health aspects Heat shock proteins HSP90 Heat-Shock Proteins - genetics Hsp90 protein Humans Hybridization Immunology Kinases Lung cancer Lung diseases Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - secondary Male Medical research Medical treatment Mutation Neoplasm Staging Non-small cell lung cancer Non-small cell lung carcinoma Oligonucleotide Array Sequence Analysis Oncology Oncology/Lung Cancer Pathology Patients Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism Signal transduction Small cell lung cancer Survival Survival Rate Thyroid cancer Tumor Cells, Cultured Tumorigenesis Tumors |
| title | Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target |
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