M Teresa Agulló-Ortuño1,2,3, Inmaculada García-Ruiz4, C Vanesa Díaz-García4, Ana B Enguita5, Virginia Pardo-Marqués4, Elena Prieto-García4, Santiago Ponce6,7, Lara Iglesias6,7, Jon Zugazagoitia6,7, José A López-Martín4,6,7, Luis Paz-Ares4,6,8,7,9, Juan A Nuñez7. 1. Laboratory of Clinical and Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12), Avda de Córdoba s/n, 28041, Madrid, Spain. agullo@h12o.es. 2. Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fernández Almagro, 3, 28029, Madrid, Spain. agullo@h12o.es. 3. Biomedical Research Networking Centre: Oncology (CIBERONC), Instituto de Salud Carlos III, C. Monforte de Lemos, 3, 28029, Madrid, Spain. agullo@h12o.es. 4. Laboratory of Clinical and Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12), Avda de Córdoba s/n, 28041, Madrid, Spain. 5. Pathology Department, Hospital Universitario 12 de Octubre, Avda de Córdoba s/n, 28041, Madrid, Spain. 6. Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fernández Almagro, 3, 28029, Madrid, Spain. 7. Medical Oncology Department, Hospital Universitario 12 de Octubre, Avda de Córdoba s/n, 28041, Madrid, Spain. 8. Biomedical Research Networking Centre: Oncology (CIBERONC), Instituto de Salud Carlos III, C. Monforte de Lemos, 3, 28029, Madrid, Spain. 9. Medicine Department, Facultad de Medicina y Cirugía, Universidad Complutense de Madrid (UCM), Avda de Séneca, 2, 28040, Madrid, Spain.
Abstract
PURPOSE: Therapeutic options for cancer patients have increased in the last years, although drugs resistance problem remains unresolved. Genetic background in individual susceptibility to cancer treatment could influence the therapy responses. The aim of this study was to explore the feasibility of using blood 4 genes (AEG-1, BRCA-1, REV3L and TYMS) expression levels as a predictor of the efficacy of pemetrexed therapy in patients with advanced non-small cell lung cancer. METHODS: Sixteen patients from the Medical Oncology Department at "12 de Octubre" Hospital, were included in the study. Total mRNA was isolated from blood samples, and gene expression was analyzed by RT-qPCR. A panel of lung tumor cell lines were used in cell proliferation tests and siRNA-mediated silencing assays. RESULTS: Similarity between blood gene expression levels and protein expression in matched tumor tissue was observed in 54.54% (REV3L) and 81.81% (TYMS) of cases. Gene expression of REV3L and TYMS in blood correlated directly and inversely, respectively, with progression-free survival and overall survival in the patients from our cohort. In tumor cell lines, the knockdown of REV3L conferred resistance to pemetrexed treatment, and the TYMS silencing increased the pemetrexed sensitivity of tumor cells. CONCLUSIONS: The use of peripheral blood samples for expression quantification of interest genes is an affordable method with promising results in the evaluation of response to pemetrexed treatment. Therefore, expression levels of REV3L and TYMS genes might be used as predictive biomarkers in advanced NSCLC patients.
PURPOSE: Therapeutic options for cancerpatients have increased in the last years, although drugs resistance problem remains unresolved. Genetic background in individual susceptibility to cancer treatment could influence the therapy responses. The aim of this study was to explore the feasibility of using blood 4 genes (AEG-1, BRCA-1, REV3L and TYMS) expression levels as a predictor of the efficacy of pemetrexed therapy in patients with advanced non-small cell lung cancer. METHODS: Sixteen patients from the Medical Oncology Department at "12 de Octubre" Hospital, were included in the study. Total mRNA was isolated from blood samples, and gene expression was analyzed by RT-qPCR. A panel of lung tumor cell lines were used in cell proliferation tests and siRNA-mediated silencing assays. RESULTS: Similarity between blood gene expression levels and protein expression in matched tumor tissue was observed in 54.54% (REV3L) and 81.81% (TYMS) of cases. Gene expression of REV3L and TYMS in blood correlated directly and inversely, respectively, with progression-free survival and overall survival in the patients from our cohort. In tumor cell lines, the knockdown of REV3L conferred resistance to pemetrexed treatment, and the TYMS silencing increased the pemetrexed sensitivity of tumor cells. CONCLUSIONS: The use of peripheral blood samples for expression quantification of interest genes is an affordable method with promising results in the evaluation of response to pemetrexed treatment. Therefore, expression levels of REV3L and TYMS genes might be used as predictive biomarkers in advanced NSCLCpatients.
Entities:
Keywords:
Non-small cell lung cancer; Pemetrexed; Predictive biomarkers; Protein reversion less 3-like; Thymidylate synthase
Authors: S Novello; F Barlesi; R Califano; T Cufer; S Ekman; M Giaj Levra; K Kerr; S Popat; M Reck; S Senan; G V Simo; J Vansteenkiste; S Peters Journal: Ann Oncol Date: 2016-09 Impact factor: 32.976
Authors: K Nakagawa; E B Garon; L Paz-Ares; S Ponce; J Corral Jaime; O Juan Vidal; E Nadal; K Kiura; S He; J Treat; R Dalal; P Lee; M Reck; S Novello Journal: Ann Oncol Date: 2017-10 Impact factor: 32.976
Authors: Martin Reck; Delvys Rodríguez-Abreu; Andrew G Robinson; Rina Hui; Tibor Csőszi; Andrea Fülöp; Maya Gottfried; Nir Peled; Ali Tafreshi; Sinead Cuffe; Mary O'Brien; Suman Rao; Katsuyuki Hotta; Melanie A Leiby; Gregory M Lubiniecki; Yue Shentu; Reshma Rangwala; Julie R Brahmer Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: M Hata; I Koike; H Wada; E Miyagi; T Kasuya; H Kaizu; T Matsui; Y Mukai; E Ito; T Inoue Journal: Ann Oncol Date: 2013-12-03 Impact factor: 32.976
Authors: James Chih-Hsin Yang; Vera Hirsh; Martin Schuler; Nobuyuki Yamamoto; Kenneth J O'Byrne; Tony S K Mok; Victoria Zazulina; Mehdi Shahidi; Juliane Lungershausen; Dan Massey; Michael Palmer; Lecia V Sequist Journal: J Clin Oncol Date: 2013-07-01 Impact factor: 44.544
Authors: Kimberly D Miller; Rebecca L Siegel; Chun Chieh Lin; Angela B Mariotto; Joan L Kramer; Julia H Rowland; Kevin D Stein; Rick Alteri; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2016-06-02 Impact factor: 508.702
Authors: Sha Yao; Luogen Peng; Omar Elakad; Stefan Küffer; Marc Hinterthaner; Bernhard C Danner; Alexander von Hammerstein-Equord; Philipp Ströbel; Hanibal Bohnenberger Journal: Transl Lung Cancer Res Date: 2021-06