Gene expression from bronchoscopy obtained tumour samples as a predictor of outcome in advanced inoperable lung cancer

Several studies have shown the prognostic and predictive potential of molecular markers in combined therapy for lung cancer. Most of them referred, however, to operable early stage NSCLC. The aim of the present study is to correlate the expression of multiple mRNA markers in bronchoscopy obtained ca...

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Veröffentlicht in:PloS one 2012-07, Vol.7 (7), p.e41379-e41379
Hauptverfasser: Suwinski, Rafal, Klusek, Artur, Tyszkiewicz, Tomasz, Kowalska, Maria, Szczesniak-Klusek, Bogna, Gawkowska-Suwinska, Marzena, Tukiendorf, Andrzej, Kozielski, Jerzy, Jarzab, Michal
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container_title PloS one
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creator Suwinski, Rafal
Klusek, Artur
Tyszkiewicz, Tomasz
Kowalska, Maria
Szczesniak-Klusek, Bogna
Gawkowska-Suwinska, Marzena
Tukiendorf, Andrzej
Kozielski, Jerzy
Jarzab, Michal
description Several studies have shown the prognostic and predictive potential of molecular markers in combined therapy for lung cancer. Most of them referred, however, to operable early stage NSCLC. The aim of the present study is to correlate the expression of multiple mRNA markers in bronchoscopy obtained cancer specimens with clinical outcome of advanced lung cancer. Bronchoscopy cancer specimens were taken from 123 patients with radiological diagnosis of advanced lung tumor. Out of 123 patients 50 were diagnosed with squamous cell cancer, 17 with adenocarcinoma, 12 with NOS, 32 with SCLC and one with large cell neuroendocrinal cancer. In 11 patients other tumours were diagnosed. The group was heterogeneous with respect to clinical stage, performance of the patients and treatment. Quantitative real time PCR was carried out by ABI 7900 HT machine, with Universal Probe Library (Roche) fluorescent probes. The genes selected for the analysis were ERCC1, EGFR, BRCA1, CSF1, CA9, DUSP6, STAT1, ERBB3, MMD, FN1, and CDKN1B. More than 50 ng of RNA (the amount considered sufficient for the analysis) was isolated in 82 out of 112 lung cancer specimens (73%), including 60/80 (75.0%) of NSCLC specimens and 22/32 (68,7%) of SCLC samples. The highest Cohen's κ coefficient for discrimination between small cell, squamous cell and adenocarcinoma was found for CDKN1B, CSF and EGFR1 (κ = 0.177, p = 0.0041). A multivariate Cox regression model has shown a significant impact of clinical stage (p
doi_str_mv 10.1371/journal.pone.0041379
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Most of them referred, however, to operable early stage NSCLC. The aim of the present study is to correlate the expression of multiple mRNA markers in bronchoscopy obtained cancer specimens with clinical outcome of advanced lung cancer. Bronchoscopy cancer specimens were taken from 123 patients with radiological diagnosis of advanced lung tumor. Out of 123 patients 50 were diagnosed with squamous cell cancer, 17 with adenocarcinoma, 12 with NOS, 32 with SCLC and one with large cell neuroendocrinal cancer. In 11 patients other tumours were diagnosed. The group was heterogeneous with respect to clinical stage, performance of the patients and treatment. Quantitative real time PCR was carried out by ABI 7900 HT machine, with Universal Probe Library (Roche) fluorescent probes. The genes selected for the analysis were ERCC1, EGFR, BRCA1, CSF1, CA9, DUSP6, STAT1, ERBB3, MMD, FN1, and CDKN1B. More than 50 ng of RNA (the amount considered sufficient for the analysis) was isolated in 82 out of 112 lung cancer specimens (73%), including 60/80 (75.0%) of NSCLC specimens and 22/32 (68,7%) of SCLC samples. The highest Cohen's κ coefficient for discrimination between small cell, squamous cell and adenocarcinoma was found for CDKN1B, CSF and EGFR1 (κ = 0.177, p = 0.0041). A multivariate Cox regression model has shown a significant impact of clinical stage (p&lt;0.001, RR = 4.19), ERCC1 (p = 0.01, RR = 0.43) and CA9 (p = 0.03, RR = 2.11) expression on overall survival in a group of 60 patients with NSCLC. These results show the feasibility of multiple gene expression analysis in bronchoscopy obtained cancer specimens as prognostic markers in radiotherapy and chemotherapy for advanced lung cancer. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Suwinski et al 2012 Suwinski et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-5a1e513d1ebbbeb3bd49e2f3e0d5e002bd5844e5ba0c89c8c150533f4f55103</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407200/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407200/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22848476$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Navarro, Alfons</contributor><creatorcontrib>Suwinski, Rafal</creatorcontrib><creatorcontrib>Klusek, Artur</creatorcontrib><creatorcontrib>Tyszkiewicz, Tomasz</creatorcontrib><creatorcontrib>Kowalska, Maria</creatorcontrib><creatorcontrib>Szczesniak-Klusek, Bogna</creatorcontrib><creatorcontrib>Gawkowska-Suwinska, Marzena</creatorcontrib><creatorcontrib>Tukiendorf, Andrzej</creatorcontrib><creatorcontrib>Kozielski, Jerzy</creatorcontrib><creatorcontrib>Jarzab, Michal</creatorcontrib><title>Gene expression from bronchoscopy obtained tumour samples as a predictor of outcome in advanced inoperable lung cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Several studies have shown the prognostic and predictive potential of molecular markers in combined therapy for lung cancer. Most of them referred, however, to operable early stage NSCLC. The aim of the present study is to correlate the expression of multiple mRNA markers in bronchoscopy obtained cancer specimens with clinical outcome of advanced lung cancer. Bronchoscopy cancer specimens were taken from 123 patients with radiological diagnosis of advanced lung tumor. Out of 123 patients 50 were diagnosed with squamous cell cancer, 17 with adenocarcinoma, 12 with NOS, 32 with SCLC and one with large cell neuroendocrinal cancer. In 11 patients other tumours were diagnosed. The group was heterogeneous with respect to clinical stage, performance of the patients and treatment. Quantitative real time PCR was carried out by ABI 7900 HT machine, with Universal Probe Library (Roche) fluorescent probes. The genes selected for the analysis were ERCC1, EGFR, BRCA1, CSF1, CA9, DUSP6, STAT1, ERBB3, MMD, FN1, and CDKN1B. More than 50 ng of RNA (the amount considered sufficient for the analysis) was isolated in 82 out of 112 lung cancer specimens (73%), including 60/80 (75.0%) of NSCLC specimens and 22/32 (68,7%) of SCLC samples. The highest Cohen's κ coefficient for discrimination between small cell, squamous cell and adenocarcinoma was found for CDKN1B, CSF and EGFR1 (κ = 0.177, p = 0.0041). A multivariate Cox regression model has shown a significant impact of clinical stage (p&lt;0.001, RR = 4.19), ERCC1 (p = 0.01, RR = 0.43) and CA9 (p = 0.03, RR = 2.11) expression on overall survival in a group of 60 patients with NSCLC. These results show the feasibility of multiple gene expression analysis in bronchoscopy obtained cancer specimens as prognostic markers in radiotherapy and chemotherapy for advanced lung cancer. A limiting factor was relatively high proportion of samples from which sufficient amount of RNA could not be isolated.</description><subject>Adenocarcinoma</subject><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Biology</subject><subject>BRCA1 protein</subject><subject>Breast cancer</subject><subject>Bronchoscopy</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cerebrospinal fluid</subject><subject>Chemotherapy</subject><subject>Correlation analysis</subject><subject>Cyclin-dependent kinases</subject><subject>Disease-Free Survival</subject><subject>DNA probes</subject><subject>Endocrinology</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB-3 protein</subject><subject>ERCC1 protein</subject><subject>Feasibility studies</subject><subject>Female</subject><subject>Fibronectins</subject><subject>Fluorescence</subject><subject>Fluorescent indicators</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>Genetic research</subject><subject>Humans</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung diseases</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Markers</subject><subject>Medical diagnosis</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - biosynthesis</subject><subject>Nitric-oxide synthase</subject><subject>Non-small cell lung cancer</subject><subject>Non-small cell lung carcinoma</subject><subject>Nuclear medicine</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Radiation therapy</subject><subject>Radiotherapy</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Small cell lung carcinoma</subject><subject>Stat1 protein</subject><subject>Surgery</subject><subject>Survival Rate</subject><subject>Teaching 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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>ProQuest Central China</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>Suwinski, Rafal</au><au>Klusek, Artur</au><au>Tyszkiewicz, Tomasz</au><au>Kowalska, Maria</au><au>Szczesniak-Klusek, Bogna</au><au>Gawkowska-Suwinska, Marzena</au><au>Tukiendorf, Andrzej</au><au>Kozielski, Jerzy</au><au>Jarzab, Michal</au><au>Navarro, Alfons</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene expression from bronchoscopy obtained tumour samples as a predictor of outcome in advanced inoperable lung cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-07-27</date><risdate>2012</risdate><volume>7</volume><issue>7</issue><spage>e41379</spage><epage>e41379</epage><pages>e41379-e41379</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Several studies have shown the prognostic and predictive potential of molecular markers in combined therapy for lung cancer. Most of them referred, however, to operable early stage NSCLC. The aim of the present study is to correlate the expression of multiple mRNA markers in bronchoscopy obtained cancer specimens with clinical outcome of advanced lung cancer. Bronchoscopy cancer specimens were taken from 123 patients with radiological diagnosis of advanced lung tumor. Out of 123 patients 50 were diagnosed with squamous cell cancer, 17 with adenocarcinoma, 12 with NOS, 32 with SCLC and one with large cell neuroendocrinal cancer. In 11 patients other tumours were diagnosed. The group was heterogeneous with respect to clinical stage, performance of the patients and treatment. Quantitative real time PCR was carried out by ABI 7900 HT machine, with Universal Probe Library (Roche) fluorescent probes. The genes selected for the analysis were ERCC1, EGFR, BRCA1, CSF1, CA9, DUSP6, STAT1, ERBB3, MMD, FN1, and CDKN1B. More than 50 ng of RNA (the amount considered sufficient for the analysis) was isolated in 82 out of 112 lung cancer specimens (73%), including 60/80 (75.0%) of NSCLC specimens and 22/32 (68,7%) of SCLC samples. The highest Cohen's κ coefficient for discrimination between small cell, squamous cell and adenocarcinoma was found for CDKN1B, CSF and EGFR1 (κ = 0.177, p = 0.0041). A multivariate Cox regression model has shown a significant impact of clinical stage (p&lt;0.001, RR = 4.19), ERCC1 (p = 0.01, RR = 0.43) and CA9 (p = 0.03, RR = 2.11) expression on overall survival in a group of 60 patients with NSCLC. These results show the feasibility of multiple gene expression analysis in bronchoscopy obtained cancer specimens as prognostic markers in radiotherapy and chemotherapy for advanced lung cancer. A limiting factor was relatively high proportion of samples from which sufficient amount of RNA could not be isolated.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22848476</pmid><doi>10.1371/journal.pone.0041379</doi><tpages>e41379</tpages><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma
Adult
Aged
Analysis
Biology
BRCA1 protein
Breast cancer
Bronchoscopy
Cancer
Care and treatment
Cerebrospinal fluid
Chemotherapy
Correlation analysis
Cyclin-dependent kinases
Disease-Free Survival
DNA probes
Endocrinology
Epidermal growth factor receptors
ErbB-3 protein
ERCC1 protein
Feasibility studies
Female
Fibronectins
Fluorescence
Fluorescent indicators
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes
Genetic research
Humans
Kinases
Lung cancer
Lung diseases
Lung Neoplasms - metabolism
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Male
Markers
Medical diagnosis
Medical prognosis
Medicine
Middle Aged
Neoplasm Proteins - biosynthesis
Nitric-oxide synthase
Non-small cell lung cancer
Non-small cell lung carcinoma
Nuclear medicine
Oncology
Pathology
Patient outcomes
Patients
Radiation therapy
Radiotherapy
Regression analysis
Regression models
Ribonucleic acid
RNA
Small cell lung carcinoma
Stat1 protein
Surgery
Survival Rate
Teaching hospitals
Tumors
title Gene expression from bronchoscopy obtained tumour samples as a predictor of outcome in advanced inoperable lung cancer
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