5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging
IntroductionPrognostic biomarkers have been very elusive in the lung squamous cell carcinoma (SCC) and none is currently being used in the clinical setting. We aimed to identify and validate the clinical utility of a protein-based prognostic signature to stratify patients with early lung SCC accordi...
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| Veröffentlicht in: | Thorax 2019-04, Vol.74 (4), p.371-379 |
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| creator | Martínez-Terroba, Elena Behrens, Carmen Agorreta, Jackeline Monsó, Eduard Millares, Laura Felip, Enriqueta Rosell, Rafael Ramirez, José Luis Remirez, Ana Torre, Wenceslao Gil-Bazo, Ignacio Idoate, Miguel A de-Torres, Juan P Pio, Ruben Wistuba, Ignacio I Pajares, María J Montuenga, Luis M |
| description | IntroductionPrognostic biomarkers have been very elusive in the lung squamous cell carcinoma (SCC) and none is currently being used in the clinical setting. We aimed to identify and validate the clinical utility of a protein-based prognostic signature to stratify patients with early lung SCC according to their risk of recurrence or death.MethodsPatients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (eighth edition, 2018). Three independent retrospective cohorts of 117, 96 and 105 patients with lung SCC were analysed to develop and validate a prognostic signature based on immunohistochemistry for five proteins.ResultsWe identified a five protein-based signature whose prognostic index (PI) was an independent and significant predictor of disease-free survival (DFS) (p |
| doi_str_mv | 10.1136/thoraxjnl-2018-212194 |
| format | Article |
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We aimed to identify and validate the clinical utility of a protein-based prognostic signature to stratify patients with early lung SCC according to their risk of recurrence or death.MethodsPatients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (eighth edition, 2018). Three independent retrospective cohorts of 117, 96 and 105 patients with lung SCC were analysed to develop and validate a prognostic signature based on immunohistochemistry for five proteins.ResultsWe identified a five protein-based signature whose prognostic index (PI) was an independent and significant predictor of disease-free survival (DFS) (p<0.001; HR=4.06, 95% CI 2.18 to 7.56) and overall survival (OS) (p=0.004; HR=2.38, 95% CI 1.32 to 4.31). The prognostic capability of PI was confirmed in an external multi-institutional cohort for DFS (p=0.042; HR=2.01, 95% CI 1.03 to 3.94) and for OS (p=0.031; HR=2.29, 95% CI 1.08 to 4.86). Moreover, PI added complementary information to the newly established IASLC TNM 8th edition staging system. A combined prognostic model including both molecular and anatomical (TNM) criteria improved the risk stratification in both cohorts (p<0.05).ConclusionWe have identified and validated a clinically feasible protein-based prognostic model that complements the updated TNM system allowing more accurate risk stratification. This signature may be used as an advantageous tool to improve the clinical management of the patients, allowing the reduction of lung SCC mortality through a more accurate knowledge of the patient’s potential outcome.</description><identifier>ISSN: 0040-6376</identifier><identifier>EISSN: 1468-3296</identifier><identifier>DOI: 10.1136/thoraxjnl-2018-212194</identifier><identifier>PMID: 30472670</identifier><language>eng</language><publisher>England: BMJ Publishing Group Ltd and British Thoracic Society</publisher><subject>Cancer therapies ; Chemotherapy ; clinical utility ; disease-free survival ; Gene expression ; Histology ; immunohistochemistry ; Lung cancer ; Medical prognosis ; Medical screening ; Metastasis ; overall survival ; prognosis ; Proteins ; Ribonucleotide reductase ; signature ; Squamous cell carcinoma ; Surgery ; Tumors</subject><ispartof>Thorax, 2019-04, Vol.74 (4), p.371-379</ispartof><rights>Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2019 Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b467t-f63eb18482f8182bdd58cd349b74a609d5ed6795e1920a56b203008d3c08cb523</citedby><cites>FETCH-LOGICAL-b467t-f63eb18482f8182bdd58cd349b74a609d5ed6795e1920a56b203008d3c08cb523</cites><orcidid>0000-0003-1231-4894 ; 0000-0003-4503-9884</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30472670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martínez-Terroba, Elena</creatorcontrib><creatorcontrib>Behrens, Carmen</creatorcontrib><creatorcontrib>Agorreta, Jackeline</creatorcontrib><creatorcontrib>Monsó, Eduard</creatorcontrib><creatorcontrib>Millares, Laura</creatorcontrib><creatorcontrib>Felip, Enriqueta</creatorcontrib><creatorcontrib>Rosell, Rafael</creatorcontrib><creatorcontrib>Ramirez, José Luis</creatorcontrib><creatorcontrib>Remirez, Ana</creatorcontrib><creatorcontrib>Torre, Wenceslao</creatorcontrib><creatorcontrib>Gil-Bazo, Ignacio</creatorcontrib><creatorcontrib>Idoate, Miguel A</creatorcontrib><creatorcontrib>de-Torres, Juan P</creatorcontrib><creatorcontrib>Pio, Ruben</creatorcontrib><creatorcontrib>Wistuba, Ignacio I</creatorcontrib><creatorcontrib>Pajares, María J</creatorcontrib><creatorcontrib>Montuenga, Luis M</creatorcontrib><title>5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging</title><title>Thorax</title><addtitle>Thorax</addtitle><addtitle>Thorax</addtitle><description>IntroductionPrognostic biomarkers have been very elusive in the lung squamous cell carcinoma (SCC) and none is currently being used in the clinical setting. We aimed to identify and validate the clinical utility of a protein-based prognostic signature to stratify patients with early lung SCC according to their risk of recurrence or death.MethodsPatients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (eighth edition, 2018). Three independent retrospective cohorts of 117, 96 and 105 patients with lung SCC were analysed to develop and validate a prognostic signature based on immunohistochemistry for five proteins.ResultsWe identified a five protein-based signature whose prognostic index (PI) was an independent and significant predictor of disease-free survival (DFS) (p<0.001; HR=4.06, 95% CI 2.18 to 7.56) and overall survival (OS) (p=0.004; HR=2.38, 95% CI 1.32 to 4.31). The prognostic capability of PI was confirmed in an external multi-institutional cohort for DFS (p=0.042; HR=2.01, 95% CI 1.03 to 3.94) and for OS (p=0.031; HR=2.29, 95% CI 1.08 to 4.86). Moreover, PI added complementary information to the newly established IASLC TNM 8th edition staging system. A combined prognostic model including both molecular and anatomical (TNM) criteria improved the risk stratification in both cohorts (p<0.05).ConclusionWe have identified and validated a clinically feasible protein-based prognostic model that complements the updated TNM system allowing more accurate risk stratification. This signature may be used as an advantageous tool to improve the clinical management of the patients, allowing the reduction of lung SCC mortality through a more accurate knowledge of the patient’s potential outcome.</description><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>clinical utility</subject><subject>disease-free survival</subject><subject>Gene expression</subject><subject>Histology</subject><subject>immunohistochemistry</subject><subject>Lung cancer</subject><subject>Medical prognosis</subject><subject>Medical screening</subject><subject>Metastasis</subject><subject>overall survival</subject><subject>prognosis</subject><subject>Proteins</subject><subject>Ribonucleotide reductase</subject><subject>signature</subject><subject>Squamous cell carcinoma</subject><subject>Surgery</subject><subject>Tumors</subject><issn>0040-6376</issn><issn>1468-3296</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNqNkUtv1DAUhS1ERYfCTwBZYsMm9PoRx1miipdUyqasI9u5STNK7KntVCDx4_F0yiCxQF154e98OleHkFcM3jEm1Hm-CdH82Pq54sB0xRlnrXxCNkwqXQneqqdkAyChUqJRp-R5SlsA0Iw1z8ipANlw1cCG_KrpLoaMk6-sSdjTNI3e5DUiHUKkERO6bOyMdF79SNPtapawJupwnqkz0U0-LIZOS7HcYaL5BvfC0YeUJ0d3GItmMd4hDcP97_XVV5qyGSc_viAng5kTvnx4z8j3jx-uLz5Xl98-fbl4f1lZqZpcDUqgZVpqPmimue37WrteyNY20iho-xp71bQ1spaDqZXlIMqpvXCgna25OCNvD97S7HbFlLtlSvsLjMdyTMeZ0FCD5qqgb_5Bt2GNvrQrVMt4I_m9sD5QLoaUIg7dLk6LiT87Bt1-nu44T7efpzvMU3KvH-yrXbA_pv7sUQA4AHbZPtrJ_kaOZf-f-Q1I1q6L</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Martínez-Terroba, Elena</creator><creator>Behrens, Carmen</creator><creator>Agorreta, Jackeline</creator><creator>Monsó, Eduard</creator><creator>Millares, Laura</creator><creator>Felip, Enriqueta</creator><creator>Rosell, Rafael</creator><creator>Ramirez, José Luis</creator><creator>Remirez, Ana</creator><creator>Torre, Wenceslao</creator><creator>Gil-Bazo, Ignacio</creator><creator>Idoate, Miguel A</creator><creator>de-Torres, Juan P</creator><creator>Pio, Ruben</creator><creator>Wistuba, Ignacio I</creator><creator>Pajares, María J</creator><creator>Montuenga, Luis M</creator><general>BMJ Publishing Group Ltd and British Thoracic Society</general><general>BMJ Publishing Group LTD</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1231-4894</orcidid><orcidid>https://orcid.org/0000-0003-4503-9884</orcidid></search><sort><creationdate>20190401</creationdate><title>5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging</title><author>Martínez-Terroba, Elena ; Behrens, Carmen ; Agorreta, Jackeline ; Monsó, Eduard ; Millares, Laura ; Felip, Enriqueta ; Rosell, Rafael ; Ramirez, José Luis ; Remirez, Ana ; Torre, Wenceslao ; Gil-Bazo, Ignacio ; Idoate, Miguel A ; de-Torres, Juan P ; Pio, Ruben ; Wistuba, Ignacio I ; Pajares, María J ; Montuenga, Luis M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b467t-f63eb18482f8182bdd58cd349b74a609d5ed6795e1920a56b203008d3c08cb523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>clinical utility</topic><topic>disease-free survival</topic><topic>Gene expression</topic><topic>Histology</topic><topic>immunohistochemistry</topic><topic>Lung cancer</topic><topic>Medical prognosis</topic><topic>Medical screening</topic><topic>Metastasis</topic><topic>overall survival</topic><topic>prognosis</topic><topic>Proteins</topic><topic>Ribonucleotide reductase</topic><topic>signature</topic><topic>Squamous cell carcinoma</topic><topic>Surgery</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martínez-Terroba, Elena</creatorcontrib><creatorcontrib>Behrens, Carmen</creatorcontrib><creatorcontrib>Agorreta, Jackeline</creatorcontrib><creatorcontrib>Monsó, Eduard</creatorcontrib><creatorcontrib>Millares, Laura</creatorcontrib><creatorcontrib>Felip, Enriqueta</creatorcontrib><creatorcontrib>Rosell, Rafael</creatorcontrib><creatorcontrib>Ramirez, José Luis</creatorcontrib><creatorcontrib>Remirez, Ana</creatorcontrib><creatorcontrib>Torre, Wenceslao</creatorcontrib><creatorcontrib>Gil-Bazo, Ignacio</creatorcontrib><creatorcontrib>Idoate, Miguel A</creatorcontrib><creatorcontrib>de-Torres, Juan P</creatorcontrib><creatorcontrib>Pio, Ruben</creatorcontrib><creatorcontrib>Wistuba, Ignacio I</creatorcontrib><creatorcontrib>Pajares, María J</creatorcontrib><creatorcontrib>Montuenga, Luis M</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><jtitle>Thorax</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martínez-Terroba, Elena</au><au>Behrens, Carmen</au><au>Agorreta, Jackeline</au><au>Monsó, Eduard</au><au>Millares, Laura</au><au>Felip, Enriqueta</au><au>Rosell, Rafael</au><au>Ramirez, José Luis</au><au>Remirez, Ana</au><au>Torre, Wenceslao</au><au>Gil-Bazo, Ignacio</au><au>Idoate, Miguel A</au><au>de-Torres, Juan P</au><au>Pio, Ruben</au><au>Wistuba, Ignacio I</au><au>Pajares, María J</au><au>Montuenga, Luis M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging</atitle><jtitle>Thorax</jtitle><stitle>Thorax</stitle><addtitle>Thorax</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>74</volume><issue>4</issue><spage>371</spage><epage>379</epage><pages>371-379</pages><issn>0040-6376</issn><eissn>1468-3296</eissn><abstract>IntroductionPrognostic biomarkers have been very elusive in the lung squamous cell carcinoma (SCC) and none is currently being used in the clinical setting. We aimed to identify and validate the clinical utility of a protein-based prognostic signature to stratify patients with early lung SCC according to their risk of recurrence or death.MethodsPatients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (eighth edition, 2018). Three independent retrospective cohorts of 117, 96 and 105 patients with lung SCC were analysed to develop and validate a prognostic signature based on immunohistochemistry for five proteins.ResultsWe identified a five protein-based signature whose prognostic index (PI) was an independent and significant predictor of disease-free survival (DFS) (p<0.001; HR=4.06, 95% CI 2.18 to 7.56) and overall survival (OS) (p=0.004; HR=2.38, 95% CI 1.32 to 4.31). The prognostic capability of PI was confirmed in an external multi-institutional cohort for DFS (p=0.042; HR=2.01, 95% CI 1.03 to 3.94) and for OS (p=0.031; HR=2.29, 95% CI 1.08 to 4.86). Moreover, PI added complementary information to the newly established IASLC TNM 8th edition staging system. A combined prognostic model including both molecular and anatomical (TNM) criteria improved the risk stratification in both cohorts (p<0.05).ConclusionWe have identified and validated a clinically feasible protein-based prognostic model that complements the updated TNM system allowing more accurate risk stratification. This signature may be used as an advantageous tool to improve the clinical management of the patients, allowing the reduction of lung SCC mortality through a more accurate knowledge of the patient’s potential outcome.</abstract><cop>England</cop><pub>BMJ Publishing Group Ltd and British Thoracic Society</pub><pmid>30472670</pmid><doi>10.1136/thoraxjnl-2018-212194</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-1231-4894</orcidid><orcidid>https://orcid.org/0000-0003-4503-9884</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cancer therapies Chemotherapy clinical utility disease-free survival Gene expression Histology immunohistochemistry Lung cancer Medical prognosis Medical screening Metastasis overall survival prognosis Proteins Ribonucleotide reductase signature Squamous cell carcinoma Surgery Tumors |
| title | 5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging |
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