Genetic alterations of driver genes as independent prognostic factors for disease-free survival in patients with resected non-small cell lung cancer
•Driver genes give a selective growth advantage to tumor cells, leading to uncontrolled cell growth and proliferation.•Gene alterations detected in 138 cancer-related genes listed in Vogelstein et al. were evaluated as driver gene alterations.•The driver gene alteration status may be an independent...
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| creator | Ono, Akira Isaka, Mitsuhiro Serizawa, Masakuni Omae, Katsuhiro Kojima, Hideaki Nakashima, Kazuhisa Omori, Shota Wakuda, Kazushige Kenmotsu, Hirotsugu Naito, Tateaki Murakami, Haruyasu Urakami, Kenichi Nagashima, Takeshi Sugino, Takashi Kusuhara, Masatoshi Takahashi, Toshiaki Yamaguchi, Ken Ohde, Yasuhisa |
| description | •Driver genes give a selective growth advantage to tumor cells, leading to uncontrolled cell growth and proliferation.•Gene alterations detected in 138 cancer-related genes listed in Vogelstein et al. were evaluated as driver gene alterations.•The driver gene alteration status may be an independent prognostic factor of postoperative relapse-free survival in NSCLC.
This study assessed the associations between the molecular signatures and clinical information in non-small cell lung cancer (NSCLC) patients with postoperative disease-free survival (p-dfs) to identify novel prognostic factors, focusing on associations with driver gene alterations.
Between February 2014 and September 2015, 242 patients with NSCLC, including 192 patients with adenocarcinoma (Ad) and 50 patients with squamous cell carcinoma (Sq), underwent surgery and were enrolled in this study. Surgically resected tissues were subjected to whole exome sequencing. Mt detected in 138 cancer-related genes were evaluated as driver mutations. A multivariate analysis using the multi-state model was used to establish the associations between co-variables and p-dfs.
Postoperative recurrence (p-rec) was observed in 49 (20.2%) and 19 (7.9%) patients with Ad and Sq, respectively. The median (range) follow-up period for all the censored cases was 2.5 (2.0–3.5) years. The characteristics of the patients with postoperative recurrence were as follows: median age (range), 71 (50–87) years; male, 38 (56%); smoker, 51 (75%); p-stage (I/II/III), 30 (44%)/19 (28%)/19 (28%); histological type (Ad/Sq), 49 (72%)/19 (28%); adjuvant chemotherapy (yes/no), 30 (44%)/38 (56%); and driver gene alteration (presence/absence), 65 (96%)/3 (4%). In univariate analyses, age ( |
| doi_str_mv | 10.1016/j.lungcan.2018.12.005 |
| format | Article |
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This study assessed the associations between the molecular signatures and clinical information in non-small cell lung cancer (NSCLC) patients with postoperative disease-free survival (p-dfs) to identify novel prognostic factors, focusing on associations with driver gene alterations.
Between February 2014 and September 2015, 242 patients with NSCLC, including 192 patients with adenocarcinoma (Ad) and 50 patients with squamous cell carcinoma (Sq), underwent surgery and were enrolled in this study. Surgically resected tissues were subjected to whole exome sequencing. Mt detected in 138 cancer-related genes were evaluated as driver mutations. A multivariate analysis using the multi-state model was used to establish the associations between co-variables and p-dfs.
Postoperative recurrence (p-rec) was observed in 49 (20.2%) and 19 (7.9%) patients with Ad and Sq, respectively. The median (range) follow-up period for all the censored cases was 2.5 (2.0–3.5) years. The characteristics of the patients with postoperative recurrence were as follows: median age (range), 71 (50–87) years; male, 38 (56%); smoker, 51 (75%); p-stage (I/II/III), 30 (44%)/19 (28%)/19 (28%); histological type (Ad/Sq), 49 (72%)/19 (28%); adjuvant chemotherapy (yes/no), 30 (44%)/38 (56%); and driver gene alteration (presence/absence), 65 (96%)/3 (4%). In univariate analyses, age (<70/≧70 years), smoking history (yes/no), p-stage (I, II/III), histological type (Ad/Sq), and driver mutation (presence/absence) were favorable prognostic factors (P = .017, P = .048, P = .0002, P = .006, P = .029, respectively). A multivariate analysis also revealed a significant association between the driver mutation status and p-dfs (P = .046; odds ratio [OR], 2.86; 95% confidence interval [CI], 1.02–8.08), when adjusted according to histological type (P = .10), smoking status (P = .09), gender (P = .51), age (P = .008) and p-stage (P = .00003).
The driver mutation status may be an independent prognostic factor of p-dfs in NSCLC.</description><identifier>ISSN: 0169-5002</identifier><identifier>EISSN: 1872-8332</identifier><identifier>DOI: 10.1016/j.lungcan.2018.12.005</identifier><identifier>PMID: 30553548</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - pathology ; Carcinoma, Non-Small-Cell Lung - therapy ; Disease-Free Survival ; Driver gene alterations ; Female ; Genetic Variation ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms - genetics ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Lung Neoplasms - therapy ; Male ; Middle Aged ; Neoplasm Staging ; NSCLC ; Oncogenes ; Pneumonectomy ; Prognosis ; Prognostic factor ; Treatment Outcome ; Whole Exome Sequencing</subject><ispartof>Lung cancer (Amsterdam, Netherlands), 2019-02, Vol.128, p.152-157</ispartof><rights>2018 The Authors</rights><rights>Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-3c3362bbd40d5033b989a6939e04739a58ab6e5173d565e95119dad235ee43173</citedby><cites>FETCH-LOGICAL-c412t-3c3362bbd40d5033b989a6939e04739a58ab6e5173d565e95119dad235ee43173</cites><orcidid>0000-0002-6762-8455 ; 0000-0003-2416-546X ; 0000-0001-5705-9423 ; 0000-0003-0590-9259 ; 0000-0003-4047-2929</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0169500218306913$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30553548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ono, Akira</creatorcontrib><creatorcontrib>Isaka, Mitsuhiro</creatorcontrib><creatorcontrib>Serizawa, Masakuni</creatorcontrib><creatorcontrib>Omae, Katsuhiro</creatorcontrib><creatorcontrib>Kojima, Hideaki</creatorcontrib><creatorcontrib>Nakashima, Kazuhisa</creatorcontrib><creatorcontrib>Omori, Shota</creatorcontrib><creatorcontrib>Wakuda, Kazushige</creatorcontrib><creatorcontrib>Kenmotsu, Hirotsugu</creatorcontrib><creatorcontrib>Naito, Tateaki</creatorcontrib><creatorcontrib>Murakami, Haruyasu</creatorcontrib><creatorcontrib>Urakami, Kenichi</creatorcontrib><creatorcontrib>Nagashima, Takeshi</creatorcontrib><creatorcontrib>Sugino, Takashi</creatorcontrib><creatorcontrib>Kusuhara, Masatoshi</creatorcontrib><creatorcontrib>Takahashi, Toshiaki</creatorcontrib><creatorcontrib>Yamaguchi, Ken</creatorcontrib><creatorcontrib>Ohde, Yasuhisa</creatorcontrib><title>Genetic alterations of driver genes as independent prognostic factors for disease-free survival in patients with resected non-small cell lung cancer</title><title>Lung cancer (Amsterdam, Netherlands)</title><addtitle>Lung Cancer</addtitle><description>•Driver genes give a selective growth advantage to tumor cells, leading to uncontrolled cell growth and proliferation.•Gene alterations detected in 138 cancer-related genes listed in Vogelstein et al. were evaluated as driver gene alterations.•The driver gene alteration status may be an independent prognostic factor of postoperative relapse-free survival in NSCLC.
This study assessed the associations between the molecular signatures and clinical information in non-small cell lung cancer (NSCLC) patients with postoperative disease-free survival (p-dfs) to identify novel prognostic factors, focusing on associations with driver gene alterations.
Between February 2014 and September 2015, 242 patients with NSCLC, including 192 patients with adenocarcinoma (Ad) and 50 patients with squamous cell carcinoma (Sq), underwent surgery and were enrolled in this study. Surgically resected tissues were subjected to whole exome sequencing. Mt detected in 138 cancer-related genes were evaluated as driver mutations. A multivariate analysis using the multi-state model was used to establish the associations between co-variables and p-dfs.
Postoperative recurrence (p-rec) was observed in 49 (20.2%) and 19 (7.9%) patients with Ad and Sq, respectively. The median (range) follow-up period for all the censored cases was 2.5 (2.0–3.5) years. The characteristics of the patients with postoperative recurrence were as follows: median age (range), 71 (50–87) years; male, 38 (56%); smoker, 51 (75%); p-stage (I/II/III), 30 (44%)/19 (28%)/19 (28%); histological type (Ad/Sq), 49 (72%)/19 (28%); adjuvant chemotherapy (yes/no), 30 (44%)/38 (56%); and driver gene alteration (presence/absence), 65 (96%)/3 (4%). In univariate analyses, age (<70/≧70 years), smoking history (yes/no), p-stage (I, II/III), histological type (Ad/Sq), and driver mutation (presence/absence) were favorable prognostic factors (P = .017, P = .048, P = .0002, P = .006, P = .029, respectively). A multivariate analysis also revealed a significant association between the driver mutation status and p-dfs (P = .046; odds ratio [OR], 2.86; 95% confidence interval [CI], 1.02–8.08), when adjusted according to histological type (P = .10), smoking status (P = .09), gender (P = .51), age (P = .008) and p-stage (P = .00003).
The driver mutation status may be an independent prognostic factor of p-dfs in NSCLC.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Disease-Free Survival</subject><subject>Driver gene alterations</subject><subject>Female</subject><subject>Genetic Variation</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>NSCLC</subject><subject>Oncogenes</subject><subject>Pneumonectomy</subject><subject>Prognosis</subject><subject>Prognostic factor</subject><subject>Treatment Outcome</subject><subject>Whole Exome Sequencing</subject><issn>0169-5002</issn><issn>1872-8332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2O1DAQhS0EYpqBI4C8ZJPgnziJVwiNhgFpJDawthy70riVthuX04h7cGAcdcOWTVmy31flV4-Q15y1nPH-3aFd1rh3NraC8bHlomVMPSE7Pg6iGaUUT8mu6nSjGBM35AXigTE-cKafkxvJlJKqG3fk9wNEKMFRuxTItoQUkaaZ-hzOkOm-viK1SEP0cIJaYqGnnPYx4UbN1pWUkc4pUx8QLEIzZwCKaz6Hs10qSE-1beWQ_gzlO82A4Ap4GlNs8GiXhTqoZbNDqx8H-SV5NtsF4dX1vCXfPt5_vfvUPH55-Hz34bFxHRelkU7KXkyT75hXTMpJj9r2Wmpg3SC1VaOdelB8kF71CrTiXHvrhVQAnazXt-TtpW919GMFLOYYcPuMjZBWNIKroVe9FH2VqovU5YSYYTanHI42_zKcmS0QczDXQMwWiOHC1EAq9-Y6Yp2O4P9RfxOogvcXAVSj5wDZoKvbcuBDrnsyPoX_jPgDCQyhpQ</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Ono, Akira</creator><creator>Isaka, Mitsuhiro</creator><creator>Serizawa, Masakuni</creator><creator>Omae, Katsuhiro</creator><creator>Kojima, Hideaki</creator><creator>Nakashima, Kazuhisa</creator><creator>Omori, Shota</creator><creator>Wakuda, Kazushige</creator><creator>Kenmotsu, Hirotsugu</creator><creator>Naito, Tateaki</creator><creator>Murakami, Haruyasu</creator><creator>Urakami, Kenichi</creator><creator>Nagashima, Takeshi</creator><creator>Sugino, Takashi</creator><creator>Kusuhara, Masatoshi</creator><creator>Takahashi, Toshiaki</creator><creator>Yamaguchi, Ken</creator><creator>Ohde, Yasuhisa</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><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><orcidid>https://orcid.org/0000-0002-6762-8455</orcidid><orcidid>https://orcid.org/0000-0003-2416-546X</orcidid><orcidid>https://orcid.org/0000-0001-5705-9423</orcidid><orcidid>https://orcid.org/0000-0003-0590-9259</orcidid><orcidid>https://orcid.org/0000-0003-4047-2929</orcidid></search><sort><creationdate>201902</creationdate><title>Genetic alterations of driver genes as independent prognostic factors for disease-free survival in patients with resected non-small cell lung cancer</title><author>Ono, Akira ; Isaka, Mitsuhiro ; Serizawa, Masakuni ; Omae, Katsuhiro ; Kojima, Hideaki ; Nakashima, Kazuhisa ; Omori, Shota ; Wakuda, Kazushige ; Kenmotsu, Hirotsugu ; Naito, Tateaki ; Murakami, Haruyasu ; Urakami, Kenichi ; Nagashima, Takeshi ; Sugino, Takashi ; Kusuhara, Masatoshi ; Takahashi, Toshiaki ; Yamaguchi, Ken ; Ohde, Yasuhisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-3c3362bbd40d5033b989a6939e04739a58ab6e5173d565e95119dad235ee43173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>Disease-Free Survival</topic><topic>Driver gene alterations</topic><topic>Female</topic><topic>Genetic Variation</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>NSCLC</topic><topic>Oncogenes</topic><topic>Pneumonectomy</topic><topic>Prognosis</topic><topic>Prognostic factor</topic><topic>Treatment Outcome</topic><topic>Whole Exome Sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ono, Akira</creatorcontrib><creatorcontrib>Isaka, Mitsuhiro</creatorcontrib><creatorcontrib>Serizawa, Masakuni</creatorcontrib><creatorcontrib>Omae, Katsuhiro</creatorcontrib><creatorcontrib>Kojima, Hideaki</creatorcontrib><creatorcontrib>Nakashima, Kazuhisa</creatorcontrib><creatorcontrib>Omori, Shota</creatorcontrib><creatorcontrib>Wakuda, Kazushige</creatorcontrib><creatorcontrib>Kenmotsu, Hirotsugu</creatorcontrib><creatorcontrib>Naito, Tateaki</creatorcontrib><creatorcontrib>Murakami, Haruyasu</creatorcontrib><creatorcontrib>Urakami, Kenichi</creatorcontrib><creatorcontrib>Nagashima, Takeshi</creatorcontrib><creatorcontrib>Sugino, Takashi</creatorcontrib><creatorcontrib>Kusuhara, Masatoshi</creatorcontrib><creatorcontrib>Takahashi, Toshiaki</creatorcontrib><creatorcontrib>Yamaguchi, Ken</creatorcontrib><creatorcontrib>Ohde, Yasuhisa</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Lung cancer (Amsterdam, Netherlands)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ono, Akira</au><au>Isaka, Mitsuhiro</au><au>Serizawa, Masakuni</au><au>Omae, Katsuhiro</au><au>Kojima, Hideaki</au><au>Nakashima, Kazuhisa</au><au>Omori, Shota</au><au>Wakuda, Kazushige</au><au>Kenmotsu, Hirotsugu</au><au>Naito, Tateaki</au><au>Murakami, Haruyasu</au><au>Urakami, Kenichi</au><au>Nagashima, Takeshi</au><au>Sugino, Takashi</au><au>Kusuhara, Masatoshi</au><au>Takahashi, Toshiaki</au><au>Yamaguchi, Ken</au><au>Ohde, Yasuhisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic alterations of driver genes as independent prognostic factors for disease-free survival in patients with resected non-small cell lung cancer</atitle><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle><addtitle>Lung Cancer</addtitle><date>2019-02</date><risdate>2019</risdate><volume>128</volume><spage>152</spage><epage>157</epage><pages>152-157</pages><issn>0169-5002</issn><eissn>1872-8332</eissn><abstract>•Driver genes give a selective growth advantage to tumor cells, leading to uncontrolled cell growth and proliferation.•Gene alterations detected in 138 cancer-related genes listed in Vogelstein et al. were evaluated as driver gene alterations.•The driver gene alteration status may be an independent prognostic factor of postoperative relapse-free survival in NSCLC.
This study assessed the associations between the molecular signatures and clinical information in non-small cell lung cancer (NSCLC) patients with postoperative disease-free survival (p-dfs) to identify novel prognostic factors, focusing on associations with driver gene alterations.
Between February 2014 and September 2015, 242 patients with NSCLC, including 192 patients with adenocarcinoma (Ad) and 50 patients with squamous cell carcinoma (Sq), underwent surgery and were enrolled in this study. Surgically resected tissues were subjected to whole exome sequencing. Mt detected in 138 cancer-related genes were evaluated as driver mutations. A multivariate analysis using the multi-state model was used to establish the associations between co-variables and p-dfs.
Postoperative recurrence (p-rec) was observed in 49 (20.2%) and 19 (7.9%) patients with Ad and Sq, respectively. The median (range) follow-up period for all the censored cases was 2.5 (2.0–3.5) years. The characteristics of the patients with postoperative recurrence were as follows: median age (range), 71 (50–87) years; male, 38 (56%); smoker, 51 (75%); p-stage (I/II/III), 30 (44%)/19 (28%)/19 (28%); histological type (Ad/Sq), 49 (72%)/19 (28%); adjuvant chemotherapy (yes/no), 30 (44%)/38 (56%); and driver gene alteration (presence/absence), 65 (96%)/3 (4%). In univariate analyses, age (<70/≧70 years), smoking history (yes/no), p-stage (I, II/III), histological type (Ad/Sq), and driver mutation (presence/absence) were favorable prognostic factors (P = .017, P = .048, P = .0002, P = .006, P = .029, respectively). A multivariate analysis also revealed a significant association between the driver mutation status and p-dfs (P = .046; odds ratio [OR], 2.86; 95% confidence interval [CI], 1.02–8.08), when adjusted according to histological type (P = .10), smoking status (P = .09), gender (P = .51), age (P = .008) and p-stage (P = .00003).
The driver mutation status may be an independent prognostic factor of p-dfs in NSCLC.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>30553548</pmid><doi>10.1016/j.lungcan.2018.12.005</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-6762-8455</orcidid><orcidid>https://orcid.org/0000-0003-2416-546X</orcidid><orcidid>https://orcid.org/0000-0001-5705-9423</orcidid><orcidid>https://orcid.org/0000-0003-0590-9259</orcidid><orcidid>https://orcid.org/0000-0003-4047-2929</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Lung cancer (Amsterdam, Netherlands), 2019-02, Vol.128, p.152-157 |
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| subjects | Adult Aged Aged, 80 and over Biomarkers, Tumor Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - mortality Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Non-Small-Cell Lung - therapy Disease-Free Survival Driver gene alterations Female Genetic Variation Humans Kaplan-Meier Estimate Lung Neoplasms - genetics Lung Neoplasms - mortality Lung Neoplasms - pathology Lung Neoplasms - therapy Male Middle Aged Neoplasm Staging NSCLC Oncogenes Pneumonectomy Prognosis Prognostic factor Treatment Outcome Whole Exome Sequencing |
| title | Genetic alterations of driver genes as independent prognostic factors for disease-free survival in patients with resected non-small cell lung cancer |
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