Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators

Abstract Background Mortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome. Methods Primary tumour tissue from 485...

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Veröffentlicht in:European journal of cancer (1990) 2015-09, Vol.51 (14), p.1897-1903
Hauptverfasser: Rakha, Emad, Pajares, Maria J, Ilie, Marius, Pio, Ruben, Echeveste, Jose, Hughes, Elisha, Soomro, Irshad, Long, Elodie, Idoate, Miguel A, Wagner, Susanne, Lanchbury, Jerry S, Baldwin, David R, Hofman, Paul, Montuenga, Luis M
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container_end_page 1903
container_issue 14
container_start_page 1897
container_title European journal of cancer (1990)
container_volume 51
creator Rakha, Emad
Pajares, Maria J
Ilie, Marius
Pio, Ruben
Echeveste, Jose
Hughes, Elisha
Soomro, Irshad
Long, Elodie
Idoate, Miguel A
Wagner, Susanne
Lanchbury, Jerry S
Baldwin, David R
Hofman, Paul
Montuenga, Luis M
description Abstract Background Mortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome. Methods Primary tumour tissue from 485 patients, surgically treated for stage I–II lung adenocarcinoma, was analysed for the RNA expression of 31 cell cycle progression (CCP) genes by quantitative polymerase chain reaction (PCR). The expression average, the CCP score, was combined with pathological stage into a prognostic score (PS). Cox proportional hazards regression assessed prediction of 5-year lung cancer mortality above clinical variables. The PS threshold was tested for risk discrimination by the Mantel–Cox log-rank test. Results The CCP score added significant information above clinical markers (all patients, P = 0.0029; stage I patients, P = 0.013). The prognostic score was a superior predictor of outcome compared to pathological stage alone (PS, P = 0.00084; stage, P = 0.24). Five-year lung cancer mortality was significantly different between the low-risk (90%, 95% confidence interval (CI) 81–95%), and high-risk groups (65%, 95% CI 57–72%), P = 4.2 × 10–6 ). Conclusions The CCP score is an independent prognostic marker in early stage lung adenocarcinoma. The prognostic score provides superior risk estimates than stage alone. The threefold higher risk in the high-risk group defines a subset of patients that should consider therapeutic choices to improve outcome.
doi_str_mv 10.1016/j.ejca.2015.07.015
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Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome. Methods Primary tumour tissue from 485 patients, surgically treated for stage I–II lung adenocarcinoma, was analysed for the RNA expression of 31 cell cycle progression (CCP) genes by quantitative polymerase chain reaction (PCR). The expression average, the CCP score, was combined with pathological stage into a prognostic score (PS). Cox proportional hazards regression assessed prediction of 5-year lung cancer mortality above clinical variables. The PS threshold was tested for risk discrimination by the Mantel–Cox log-rank test. Results The CCP score added significant information above clinical markers (all patients, P = 0.0029; stage I patients, P = 0.013). The prognostic score was a superior predictor of outcome compared to pathological stage alone (PS, P = 0.00084; stage, P = 0.24). Five-year lung cancer mortality was significantly different between the low-risk (90%, 95% confidence interval (CI) 81–95%), and high-risk groups (65%, 95% CI 57–72%), P = 4.2 × 10–6 ). Conclusions The CCP score is an independent prognostic marker in early stage lung adenocarcinoma. The prognostic score provides superior risk estimates than stage alone. The threefold higher risk in the high-risk group defines a subset of patients that should consider therapeutic choices to improve outcome.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2015.07.015</identifier><identifier>PMID: 26235745</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adenocarcinoma - genetics ; Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Adenocarcinoma - surgery ; Adenocarcinoma of Lung ; Biomarkers, Tumor - genetics ; Cell Cycle Proteins - genetics ; Decision Support Techniques ; Europe ; Expression signature ; Female ; Gene Expression Profiling - methods ; Hematology, Oncology and Palliative Medicine ; Humans ; Kaplan-Meier Estimate ; Lung adenocarcinoma ; Lung Neoplasms - genetics ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Lung Neoplasms - surgery ; Male ; Neoplasm Staging ; Pneumonectomy ; Polymerase Chain Reaction ; Post-surgical treatment ; Predictive Value of Tests ; Prognostic marker ; Proportional Hazards Models ; Reproducibility of Results ; Retrospective Studies ; Risk Assessment ; Risk Factors</subject><ispartof>European journal of cancer (1990), 2015-09, Vol.51 (14), p.1897-1903</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-6d25ce386460db254d077e9dd83386dc2624a7eeed0991b6adbdf2ed46f81523</citedby><cites>FETCH-LOGICAL-c477t-6d25ce386460db254d077e9dd83386dc2624a7eeed0991b6adbdf2ed46f81523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejca.2015.07.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26235745$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rakha, Emad</creatorcontrib><creatorcontrib>Pajares, Maria J</creatorcontrib><creatorcontrib>Ilie, Marius</creatorcontrib><creatorcontrib>Pio, Ruben</creatorcontrib><creatorcontrib>Echeveste, Jose</creatorcontrib><creatorcontrib>Hughes, Elisha</creatorcontrib><creatorcontrib>Soomro, Irshad</creatorcontrib><creatorcontrib>Long, Elodie</creatorcontrib><creatorcontrib>Idoate, Miguel A</creatorcontrib><creatorcontrib>Wagner, Susanne</creatorcontrib><creatorcontrib>Lanchbury, Jerry S</creatorcontrib><creatorcontrib>Baldwin, David R</creatorcontrib><creatorcontrib>Hofman, Paul</creatorcontrib><creatorcontrib>Montuenga, Luis M</creatorcontrib><title>Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Abstract Background Mortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome. Methods Primary tumour tissue from 485 patients, surgically treated for stage I–II lung adenocarcinoma, was analysed for the RNA expression of 31 cell cycle progression (CCP) genes by quantitative polymerase chain reaction (PCR). The expression average, the CCP score, was combined with pathological stage into a prognostic score (PS). Cox proportional hazards regression assessed prediction of 5-year lung cancer mortality above clinical variables. The PS threshold was tested for risk discrimination by the Mantel–Cox log-rank test. Results The CCP score added significant information above clinical markers (all patients, P = 0.0029; stage I patients, P = 0.013). The prognostic score was a superior predictor of outcome compared to pathological stage alone (PS, P = 0.00084; stage, P = 0.24). Five-year lung cancer mortality was significantly different between the low-risk (90%, 95% confidence interval (CI) 81–95%), and high-risk groups (65%, 95% CI 57–72%), P = 4.2 × 10–6 ). Conclusions The CCP score is an independent prognostic marker in early stage lung adenocarcinoma. The prognostic score provides superior risk estimates than stage alone. The threefold higher risk in the high-risk group defines a subset of patients that should consider therapeutic choices to improve outcome.</description><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - mortality</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma - surgery</subject><subject>Adenocarcinoma of Lung</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Decision Support Techniques</subject><subject>Europe</subject><subject>Expression signature</subject><subject>Female</subject><subject>Gene Expression Profiling - methods</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Lung adenocarcinoma</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - surgery</subject><subject>Male</subject><subject>Neoplasm Staging</subject><subject>Pneumonectomy</subject><subject>Polymerase Chain Reaction</subject><subject>Post-surgical treatment</subject><subject>Predictive Value of Tests</subject><subject>Prognostic marker</subject><subject>Proportional Hazards Models</subject><subject>Reproducibility of Results</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-L1TAUxYMoznP0C7iQLN203qRN0oIIMvgPBlzMrA1pcjumkzbPpB14396UN7pw4SYHwjknN79LyGsGNQMm3001TtbUHJioQdVFnpAD61RfQSf4U3KAXvRVB21_QV7kPAGA6lp4Ti645I1QrTiQHzdrMqsfvS1nXGgcacKMdjVDQBq25Y4ah0u0Jlm_xNnQ4UTnGNBuwSRqFkePZv0ZQ7wrFYEmn-8p5tXPZo0pvyTPRhMyvnrUS3L7-dPt1dfq-vuXb1cfryvbKrVW0nFhselkK8ENXLQOlMLeua4pl86WeVujENFB37NBGje4kaNr5dgxwZtL8vZce0zx11ae17PPFkMwC8Yta6ZACiVBsmLlZ6tNMeeEoz6mMmw6aQZ6x6onvWPVO1YNShcpoTeP_dswo_sb-cOxGN6fDVg--eAx6Ww9LhadTwWmdtH_v__DP3Eb_LIDvccT5iluaSn4NNOZa9A3-2L3vTIBIPuWN78BSLSfiA</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Rakha, Emad</creator><creator>Pajares, Maria J</creator><creator>Ilie, Marius</creator><creator>Pio, Ruben</creator><creator>Echeveste, Jose</creator><creator>Hughes, Elisha</creator><creator>Soomro, Irshad</creator><creator>Long, Elodie</creator><creator>Idoate, Miguel A</creator><creator>Wagner, Susanne</creator><creator>Lanchbury, Jerry S</creator><creator>Baldwin, David R</creator><creator>Hofman, Paul</creator><creator>Montuenga, Luis M</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150901</creationdate><title>Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators</title><author>Rakha, Emad ; Pajares, Maria J ; Ilie, Marius ; Pio, Ruben ; Echeveste, Jose ; Hughes, Elisha ; Soomro, Irshad ; Long, Elodie ; Idoate, Miguel A ; Wagner, Susanne ; Lanchbury, Jerry S ; Baldwin, David R ; Hofman, Paul ; Montuenga, Luis M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-6d25ce386460db254d077e9dd83386dc2624a7eeed0991b6adbdf2ed46f81523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma - surgery</topic><topic>Adenocarcinoma of Lung</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Decision Support Techniques</topic><topic>Europe</topic><topic>Expression signature</topic><topic>Female</topic><topic>Gene Expression Profiling - methods</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Lung adenocarcinoma</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - surgery</topic><topic>Male</topic><topic>Neoplasm Staging</topic><topic>Pneumonectomy</topic><topic>Polymerase Chain Reaction</topic><topic>Post-surgical treatment</topic><topic>Predictive Value of Tests</topic><topic>Prognostic marker</topic><topic>Proportional Hazards Models</topic><topic>Reproducibility of Results</topic><topic>Retrospective Studies</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rakha, Emad</creatorcontrib><creatorcontrib>Pajares, Maria J</creatorcontrib><creatorcontrib>Ilie, Marius</creatorcontrib><creatorcontrib>Pio, Ruben</creatorcontrib><creatorcontrib>Echeveste, Jose</creatorcontrib><creatorcontrib>Hughes, Elisha</creatorcontrib><creatorcontrib>Soomro, Irshad</creatorcontrib><creatorcontrib>Long, Elodie</creatorcontrib><creatorcontrib>Idoate, Miguel A</creatorcontrib><creatorcontrib>Wagner, Susanne</creatorcontrib><creatorcontrib>Lanchbury, Jerry S</creatorcontrib><creatorcontrib>Baldwin, David R</creatorcontrib><creatorcontrib>Hofman, Paul</creatorcontrib><creatorcontrib>Montuenga, Luis M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rakha, Emad</au><au>Pajares, Maria J</au><au>Ilie, Marius</au><au>Pio, Ruben</au><au>Echeveste, Jose</au><au>Hughes, Elisha</au><au>Soomro, Irshad</au><au>Long, Elodie</au><au>Idoate, Miguel A</au><au>Wagner, Susanne</au><au>Lanchbury, Jerry S</au><au>Baldwin, David R</au><au>Hofman, Paul</au><au>Montuenga, Luis M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>51</volume><issue>14</issue><spage>1897</spage><epage>1903</epage><pages>1897-1903</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Abstract Background Mortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome. Methods Primary tumour tissue from 485 patients, surgically treated for stage I–II lung adenocarcinoma, was analysed for the RNA expression of 31 cell cycle progression (CCP) genes by quantitative polymerase chain reaction (PCR). The expression average, the CCP score, was combined with pathological stage into a prognostic score (PS). Cox proportional hazards regression assessed prediction of 5-year lung cancer mortality above clinical variables. The PS threshold was tested for risk discrimination by the Mantel–Cox log-rank test. Results The CCP score added significant information above clinical markers (all patients, P = 0.0029; stage I patients, P = 0.013). The prognostic score was a superior predictor of outcome compared to pathological stage alone (PS, P = 0.00084; stage, P = 0.24). Five-year lung cancer mortality was significantly different between the low-risk (90%, 95% confidence interval (CI) 81–95%), and high-risk groups (65%, 95% CI 57–72%), P = 4.2 × 10–6 ). Conclusions The CCP score is an independent prognostic marker in early stage lung adenocarcinoma. The prognostic score provides superior risk estimates than stage alone. The threefold higher risk in the high-risk group defines a subset of patients that should consider therapeutic choices to improve outcome.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26235745</pmid><doi>10.1016/j.ejca.2015.07.015</doi><tpages>7</tpages></addata></record>
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subjects Adenocarcinoma - genetics
Adenocarcinoma - mortality
Adenocarcinoma - pathology
Adenocarcinoma - surgery
Adenocarcinoma of Lung
Biomarkers, Tumor - genetics
Cell Cycle Proteins - genetics
Decision Support Techniques
Europe
Expression signature
Female
Gene Expression Profiling - methods
Hematology, Oncology and Palliative Medicine
Humans
Kaplan-Meier Estimate
Lung adenocarcinoma
Lung Neoplasms - genetics
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Lung Neoplasms - surgery
Male
Neoplasm Staging
Pneumonectomy
Polymerase Chain Reaction
Post-surgical treatment
Predictive Value of Tests
Prognostic marker
Proportional Hazards Models
Reproducibility of Results
Retrospective Studies
Risk Assessment
Risk Factors
title Stratification of resectable lung adenocarcinoma by molecular and pathological risk estimators
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