Emad Rakha1, Maria J Pajares2, Marius Ilie3, Ruben Pio2, Jose Echeveste4, Elisha Hughes5, Irshad Soomro6, Elodie Long3, Miguel A Idoate4, Susanne Wagner5, Jerry S Lanchbury5, David R Baldwin7, Paul Hofman3, Luis M Montuenga2. 1. Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham NG7 2RD, UK; The Nottingham Health Science Biobank (NHSB), Nottingham University Hospitals NHS Trust, Nottingham NG7 2RD, UK. Electronic address: Emad.Rakha@nottingham.ac.uk. 2. Program in Solid Tumor and Biomarkers, Center for Applied Medical Research, University of Navarra, Pamplona 31008, Spain. 3. Centre Hospitalier Universitaire de Nice, Louis Pasteur Hospital, Laboratory of Clinical and Experimental Pathology, Hospital-Integrated Biobank, University of Nice Sophia Antipolis, Nice 06003, France. 4. Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain. 5. Myriad Genetics, Inc., Salt Lake City, UT 84108, USA. 6. Department of Pathology, Nottingham University Hospitals, Nottingham NG7 2RD, UK. 7. Department of Respiratory Medicine, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
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.
BACKGROUND: Mortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancerpatients 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.
Authors: Elena Martínez-Terroba; Carmen Behrens; Fernando J de Miguel; Jackeline Agorreta; Eduard Monsó; Laura Millares; Cristina Sainz; Miguel Mesa-Guzman; José Luis Pérez-Gracia; María Dolores Lozano; Javier J Zulueta; Ruben Pio; Ignacio I Wistuba; Luis M Montuenga; María J Pajares Journal: J Pathol Date: 2018-06-20 Impact factor: 7.996
Authors: Andre L Moreira; Paolo S S Ocampo; Yuhe Xia; Hua Zhong; Prudence A Russell; Yuko Minami; Wendy A Cooper; Akihiko Yoshida; Lukas Bubendorf; Mauro Papotti; Giuseppe Pelosi; Fernando Lopez-Rios; Keiko Kunitoki; Dana Ferrari-Light; Lynette M Sholl; Mary Beth Beasley; Alain Borczuk; Johan Botling; Elisabeth Brambilla; Gang Chen; Teh-Ying Chou; Jin-Haeng Chung; Sanja Dacic; Deepali Jain; Fred R Hirsch; David Hwang; Sylvie Lantuejoul; Dongmei Lin; John W Longshore; Noriko Motoi; Masayuki Noguchi; Claudia Poleri; Natasha Rekhtman; Ming-Sound Tsao; Erik Thunnissen; William D Travis; Yasushi Yatabe; Anja C Roden; Jillian B Daigneault; Ignacio I Wistuba; Keith M Kerr; Harvey Pass; Andrew G Nicholson; Mari Mino-Kenudson Journal: J Thorac Oncol Date: 2020-06-17 Impact factor: 15.609
Authors: Takashi Eguchi; Kyuichi Kadota; Jamie Chaft; Brent Evans; John Kidd; Kay See Tan; Joe Dycoco; Kathryn Kolquist; Thaylon Davis; Stephanie A Hamilton; Kraig Yager; Joshua T Jones; William D Travis; David R Jones; Anne-Renee Hartman; Prasad S Adusumilli Journal: Oncotarget Date: 2016-06-07