Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10
ObjectiveThere are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, i...
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| creator | Grieve, Stacy Ding, Keyue Moore, Jonathan Finniss, Mathew Ray, Ayush Lees, Miranda Hossain, Faisal Murugesan, Alli Agar, Jane Acar, Cenk Taylor, James Shepherd, Frances A Reiman, Tony |
| description | ObjectiveThere are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, into a readily applicable immunohistochemistry (IHC) panel.MethodsFor seven of the genes in the gene expression profile (GEP) for which suitable commercial antibodies were available, we semiquantitatively assessed the IHC expression and prognostic significance for 173 patients treated at the Saint John Regional Hospital (SJRH). Cut-offs for high and low expression were defined for each marker and applied to IHC scores from 291 of the 482 patients in JBR.10, including patients on both the adjuvant chemotherapy and observation arms. The prognostic and predictive value of these markers on overall survival (OS) or recurrence-free survival (RFS) was assessed by Cox regression models.ResultsIn the SJRH cohort, in 62 patients with resected stage II–III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with Zhu’s GEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS, HR=0.14; p |
| doi_str_mv | 10.1136/esmoopen-2020-000679 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7174014</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2059702920300697</els_id><sourcerecordid>2384205511</sourcerecordid><originalsourceid>FETCH-LOGICAL-b569t-27575151ded8d2ecd8c8fb08a634df8c0287323e240d35266d83182341e9d2d93</originalsourceid><addsrcrecordid>eNqNkc1u1DAUhS0EotXQN0DISzZp_ZNfFkhQFSiqhIRgbTn2zYwHxw62E2meiZfE0bSlXZWVLfvcc-89H0KvKTmnlNcXEEfvJ3AFI4wUhJC66Z6hU0aqrmgI654_uJ-gsxj3WUObMj_WL9EJZ4yRrmxP0Z_rcZyd35mYvNrBaJS0eJHWaJmMdzimWR-wHzCtii04wL3xowy_IOBJOrB4CqCNSmaBVdVnyWASHoIfsdT7eZEu4dXYpx0EOR2wcThABJVAY-ddEUdpbaHAWmxnt8VKOgXhHZZO2kM0cbX9-vH7OSWv0ItB2ghnt-cG_fx09ePyS3Hz7fP15Yeboq_qLhWsqZqKVlSDbjUDpVvVDj1pZc1LPbSKsLbhjAMrieYVq2vdctoyXlLoNNMd36D3R99p7kfQClwK0oopmLz5QXhpxOMfZ3Zi6xfR5IQJLbPB21uD4H_PEJMYTVw3zIn5OQrG25VElVFuUHmUquBjDDDct6FErKjFHWqxohZH1LnszcMR74vuwP7bAXJQi4EgojKQk9Um5OyF9uapDhdHg37c_99MfwGHKs8T</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2384205511</pqid></control><display><type>article</type><title>Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10</title><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Grieve, Stacy ; Ding, Keyue ; Moore, Jonathan ; Finniss, Mathew ; Ray, Ayush ; Lees, Miranda ; Hossain, Faisal ; Murugesan, Alli ; Agar, Jane ; Acar, Cenk ; Taylor, James ; Shepherd, Frances A ; Reiman, Tony</creator><creatorcontrib>Grieve, Stacy ; Ding, Keyue ; Moore, Jonathan ; Finniss, Mathew ; Ray, Ayush ; Lees, Miranda ; Hossain, Faisal ; Murugesan, Alli ; Agar, Jane ; Acar, Cenk ; Taylor, James ; Shepherd, Frances A ; Reiman, Tony</creatorcontrib><description>ObjectiveThere are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, into a readily applicable immunohistochemistry (IHC) panel.MethodsFor seven of the genes in the gene expression profile (GEP) for which suitable commercial antibodies were available, we semiquantitatively assessed the IHC expression and prognostic significance for 173 patients treated at the Saint John Regional Hospital (SJRH). Cut-offs for high and low expression were defined for each marker and applied to IHC scores from 291 of the 482 patients in JBR.10, including patients on both the adjuvant chemotherapy and observation arms. The prognostic and predictive value of these markers on overall survival (OS) or recurrence-free survival (RFS) was assessed by Cox regression models.ResultsIn the SJRH cohort, in 62 patients with resected stage II–III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with Zhu’s GEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS, HR=0.14; p<0.0001) and high STMN2 (RFS, HR=2.501; p=0.0197) were adverse prognostic factors. Low ATP1B1 and low TRIM14 expression trended toward worse OS and RFS. Validation of these markers with JBR.10 patients failed to show prognostic significance either individually or in combined risk classifications. Additionally, the interaction between these markers and chemotherapy treatment in predicting OS (FOSL2, p=0.52; STMN2 p=0.14; ATP1B1, p=0.33; TRIM14, p=0.81) or RFS (FOSL2, p=0.63; STMN2, p=0.12; ATP1B1, p=0.66; TRIM14, p=0.57) did not reach significance, individually or in combination panels.ConclusionsZhu’s GEP could not be translated into an IHC panel predictive of benefit from adjuvant chemotherapy. Future predictive biomarker analysis in the adjuvant NSCLC setting may need to focus on novel therapies.</description><identifier>ISSN: 2059-7029</identifier><identifier>EISSN: 2059-7029</identifier><identifier>DOI: 10.1136/esmoopen-2020-000679</identifier><identifier>PMID: 32220948</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>adjuvant chemotherapy ; biomarker ; gene expression profile ; immunohistochemistry ; non-small-cell lung cancer ; Original Research ; predictive</subject><ispartof>ESMO open, 2020-03, Vol.5 (2), p.e000679, Article e000679</ispartof><rights>Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.</rights><rights>2020 © 2020 THE AUTHORS. Published by Elsevier Limited on behalf of European Society for Medical Oncology.</rights><rights>Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b569t-27575151ded8d2ecd8c8fb08a634df8c0287323e240d35266d83182341e9d2d93</citedby><cites>FETCH-LOGICAL-b569t-27575151ded8d2ecd8c8fb08a634df8c0287323e240d35266d83182341e9d2d93</cites><orcidid>0000-0002-2706-8764</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174014/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174014/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32220948$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Grieve, Stacy</creatorcontrib><creatorcontrib>Ding, Keyue</creatorcontrib><creatorcontrib>Moore, Jonathan</creatorcontrib><creatorcontrib>Finniss, Mathew</creatorcontrib><creatorcontrib>Ray, Ayush</creatorcontrib><creatorcontrib>Lees, Miranda</creatorcontrib><creatorcontrib>Hossain, Faisal</creatorcontrib><creatorcontrib>Murugesan, Alli</creatorcontrib><creatorcontrib>Agar, Jane</creatorcontrib><creatorcontrib>Acar, Cenk</creatorcontrib><creatorcontrib>Taylor, James</creatorcontrib><creatorcontrib>Shepherd, Frances A</creatorcontrib><creatorcontrib>Reiman, Tony</creatorcontrib><title>Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10</title><title>ESMO open</title><addtitle>ESMO Open</addtitle><description>ObjectiveThere are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, into a readily applicable immunohistochemistry (IHC) panel.MethodsFor seven of the genes in the gene expression profile (GEP) for which suitable commercial antibodies were available, we semiquantitatively assessed the IHC expression and prognostic significance for 173 patients treated at the Saint John Regional Hospital (SJRH). Cut-offs for high and low expression were defined for each marker and applied to IHC scores from 291 of the 482 patients in JBR.10, including patients on both the adjuvant chemotherapy and observation arms. The prognostic and predictive value of these markers on overall survival (OS) or recurrence-free survival (RFS) was assessed by Cox regression models.ResultsIn the SJRH cohort, in 62 patients with resected stage II–III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with Zhu’s GEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS, HR=0.14; p<0.0001) and high STMN2 (RFS, HR=2.501; p=0.0197) were adverse prognostic factors. Low ATP1B1 and low TRIM14 expression trended toward worse OS and RFS. Validation of these markers with JBR.10 patients failed to show prognostic significance either individually or in combined risk classifications. Additionally, the interaction between these markers and chemotherapy treatment in predicting OS (FOSL2, p=0.52; STMN2 p=0.14; ATP1B1, p=0.33; TRIM14, p=0.81) or RFS (FOSL2, p=0.63; STMN2, p=0.12; ATP1B1, p=0.66; TRIM14, p=0.57) did not reach significance, individually or in combination panels.ConclusionsZhu’s GEP could not be translated into an IHC panel predictive of benefit from adjuvant chemotherapy. Future predictive biomarker analysis in the adjuvant NSCLC setting may need to focus on novel therapies.</description><subject>adjuvant chemotherapy</subject><subject>biomarker</subject><subject>gene expression profile</subject><subject>immunohistochemistry</subject><subject>non-small-cell lung cancer</subject><subject>Original Research</subject><subject>predictive</subject><issn>2059-7029</issn><issn>2059-7029</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>ACMMV</sourceid><recordid>eNqNkc1u1DAUhS0EotXQN0DISzZp_ZNfFkhQFSiqhIRgbTn2zYwHxw62E2meiZfE0bSlXZWVLfvcc-89H0KvKTmnlNcXEEfvJ3AFI4wUhJC66Z6hU0aqrmgI654_uJ-gsxj3WUObMj_WL9EJZ4yRrmxP0Z_rcZyd35mYvNrBaJS0eJHWaJmMdzimWR-wHzCtii04wL3xowy_IOBJOrB4CqCNSmaBVdVnyWASHoIfsdT7eZEu4dXYpx0EOR2wcThABJVAY-ddEUdpbaHAWmxnt8VKOgXhHZZO2kM0cbX9-vH7OSWv0ItB2ghnt-cG_fx09ePyS3Hz7fP15Yeboq_qLhWsqZqKVlSDbjUDpVvVDj1pZc1LPbSKsLbhjAMrieYVq2vdctoyXlLoNNMd36D3R99p7kfQClwK0oopmLz5QXhpxOMfZ3Zi6xfR5IQJLbPB21uD4H_PEJMYTVw3zIn5OQrG25VElVFuUHmUquBjDDDct6FErKjFHWqxohZH1LnszcMR74vuwP7bAXJQi4EgojKQk9Um5OyF9uapDhdHg37c_99MfwGHKs8T</recordid><startdate>20200326</startdate><enddate>20200326</enddate><creator>Grieve, Stacy</creator><creator>Ding, Keyue</creator><creator>Moore, Jonathan</creator><creator>Finniss, Mathew</creator><creator>Ray, Ayush</creator><creator>Lees, Miranda</creator><creator>Hossain, Faisal</creator><creator>Murugesan, Alli</creator><creator>Agar, Jane</creator><creator>Acar, Cenk</creator><creator>Taylor, James</creator><creator>Shepherd, Frances A</creator><creator>Reiman, Tony</creator><general>Elsevier Ltd</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</scope><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2706-8764</orcidid></search><sort><creationdate>20200326</creationdate><title>Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10</title><author>Grieve, Stacy ; Ding, Keyue ; Moore, Jonathan ; Finniss, Mathew ; Ray, Ayush ; Lees, Miranda ; Hossain, Faisal ; Murugesan, Alli ; Agar, Jane ; Acar, Cenk ; Taylor, James ; Shepherd, Frances A ; Reiman, Tony</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b569t-27575151ded8d2ecd8c8fb08a634df8c0287323e240d35266d83182341e9d2d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>adjuvant chemotherapy</topic><topic>biomarker</topic><topic>gene expression profile</topic><topic>immunohistochemistry</topic><topic>non-small-cell lung cancer</topic><topic>Original Research</topic><topic>predictive</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grieve, Stacy</creatorcontrib><creatorcontrib>Ding, Keyue</creatorcontrib><creatorcontrib>Moore, Jonathan</creatorcontrib><creatorcontrib>Finniss, Mathew</creatorcontrib><creatorcontrib>Ray, Ayush</creatorcontrib><creatorcontrib>Lees, Miranda</creatorcontrib><creatorcontrib>Hossain, Faisal</creatorcontrib><creatorcontrib>Murugesan, Alli</creatorcontrib><creatorcontrib>Agar, Jane</creatorcontrib><creatorcontrib>Acar, Cenk</creatorcontrib><creatorcontrib>Taylor, James</creatorcontrib><creatorcontrib>Shepherd, Frances A</creatorcontrib><creatorcontrib>Reiman, Tony</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>ESMO open</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grieve, Stacy</au><au>Ding, Keyue</au><au>Moore, Jonathan</au><au>Finniss, Mathew</au><au>Ray, Ayush</au><au>Lees, Miranda</au><au>Hossain, Faisal</au><au>Murugesan, Alli</au><au>Agar, Jane</au><au>Acar, Cenk</au><au>Taylor, James</au><au>Shepherd, Frances A</au><au>Reiman, Tony</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10</atitle><jtitle>ESMO open</jtitle><addtitle>ESMO Open</addtitle><date>2020-03-26</date><risdate>2020</risdate><volume>5</volume><issue>2</issue><spage>e000679</spage><pages>e000679-</pages><artnum>e000679</artnum><issn>2059-7029</issn><eissn>2059-7029</eissn><abstract>ObjectiveThere are no validated approaches to predict benefit from adjuvant chemotherapy for resected patients with non-small-cell lung cancer (NSCLC). The aim of this study was to translate a 15-gene mRNA expression profile published by Zhu et al, shown to be prognostic and predictive of benefit, into a readily applicable immunohistochemistry (IHC) panel.MethodsFor seven of the genes in the gene expression profile (GEP) for which suitable commercial antibodies were available, we semiquantitatively assessed the IHC expression and prognostic significance for 173 patients treated at the Saint John Regional Hospital (SJRH). Cut-offs for high and low expression were defined for each marker and applied to IHC scores from 291 of the 482 patients in JBR.10, including patients on both the adjuvant chemotherapy and observation arms. The prognostic and predictive value of these markers on overall survival (OS) or recurrence-free survival (RFS) was assessed by Cox regression models.ResultsIn the SJRH cohort, in 62 patients with resected stage II–III NSCLC, the prognostic significance of IHC assays for four proteins were concordant with Zhu’s GEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS, HR=0.14; p<0.0001) and high STMN2 (RFS, HR=2.501; p=0.0197) were adverse prognostic factors. Low ATP1B1 and low TRIM14 expression trended toward worse OS and RFS. Validation of these markers with JBR.10 patients failed to show prognostic significance either individually or in combined risk classifications. Additionally, the interaction between these markers and chemotherapy treatment in predicting OS (FOSL2, p=0.52; STMN2 p=0.14; ATP1B1, p=0.33; TRIM14, p=0.81) or RFS (FOSL2, p=0.63; STMN2, p=0.12; ATP1B1, p=0.66; TRIM14, p=0.57) did not reach significance, individually or in combination panels.ConclusionsZhu’s GEP could not be translated into an IHC panel predictive of benefit from adjuvant chemotherapy. Future predictive biomarker analysis in the adjuvant NSCLC setting may need to focus on novel therapies.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32220948</pmid><doi>10.1136/esmoopen-2020-000679</doi><orcidid>https://orcid.org/0000-0002-2706-8764</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | adjuvant chemotherapy biomarker gene expression profile immunohistochemistry non-small-cell lung cancer Original Research predictive |
| title | Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10 |
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