Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.

<h4>Background</h4>Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome to gemcitabine plus doceta...

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Autores principales:	Ioannis Boukovinas, Chara Papadaki, Pedro Mendez, Miquel Taron, Dimitris Mavroudis, Anastasios Koutsopoulos, Maria Sanchez-Ronco, Jose Javier Sanchez, Maria Trypaki, Eustathios Staphopoulos, Vassilis Georgoulias, Rafael Rosell, John Souglakos
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2d8e5149519d416eb3ee0b6442ee0a97
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spelling	oai:doaj.org-article:2d8e5149519d416eb3ee0b6442ee0a972021-11-25T06:18:34ZTumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.1932-620310.1371/journal.pone.0003695https://doaj.org/article/2d8e5149519d416eb3ee0b6442ee0a972008-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19002265/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer (NSCLC) patients.<h4>Methodology and principal findings</h4>Tumor samples were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a randomized trial. RRM1, RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response, time to progression and survival. As BRCA1 levels increased, the probability of response increased (Odds Ratio [OR], 1.09: p = 0.01) and the risk of progression decreased (hazard ratio [HR], 0.99; p = 0.36). As RRM1 and RRM2 levels increased, the probability of response decreased (RRM1: OR, 0.97; p = 0.82; RRM2: OR, 0.94; p<0.0001) and the risk of progression increased (RRM1: HR, 1.02; p = 0.001; RRM2: HR, 1.005; p = 0.01). An interaction observed between BRCA1 and RRM1 allowed patients to be classified in three risk groups according to combinations of gene expression levels, with times to progression of 10.13, 4.17 and 2.30 months (p = 0.001). Low BRCA1 expression was the only factor significantly associated with longer time to progression in 31 patients receiving cisplatin-based second-line therapy.<h4>Conclusions</h4>The mRNA expression of BRCA1, RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospective studies.Ioannis BoukovinasChara PapadakiPedro MendezMiquel TaronDimitris MavroudisAnastasios KoutsopoulosMaria Sanchez-RoncoJose Javier SanchezMaria TrypakiEustathios StaphopoulosVassilis GeorgouliasRafael RosellJohn SouglakosPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 11, p e3695 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ioannis Boukovinas Chara Papadaki Pedro Mendez Miquel Taron Dimitris Mavroudis Anastasios Koutsopoulos Maria Sanchez-Ronco Jose Javier Sanchez Maria Trypaki Eustathios Staphopoulos Vassilis Georgoulias Rafael Rosell John Souglakos Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.
description	<h4>Background</h4>Overexpression of RRM1 and RRM2 has been associated with gemcitabine resistance. BRCA1 overexpression increases sensitivity to paclitaxel and docetaxel. We have retrospectively examined the effect of RRM1, RRM2 and BRCA1 expression on outcome to gemcitabine plus docetaxel in advanced non-small-cell lung cancer (NSCLC) patients.<h4>Methodology and principal findings</h4>Tumor samples were collected from 102 chemotherapy-naïve advanced NSCLC patients treated with gemcitabine plus docetaxel as part of a randomized trial. RRM1, RRM2 and BRCA1 mRNA levels were assessed by quantitative PCR and correlated with response, time to progression and survival. As BRCA1 levels increased, the probability of response increased (Odds Ratio [OR], 1.09: p = 0.01) and the risk of progression decreased (hazard ratio [HR], 0.99; p = 0.36). As RRM1 and RRM2 levels increased, the probability of response decreased (RRM1: OR, 0.97; p = 0.82; RRM2: OR, 0.94; p<0.0001) and the risk of progression increased (RRM1: HR, 1.02; p = 0.001; RRM2: HR, 1.005; p = 0.01). An interaction observed between BRCA1 and RRM1 allowed patients to be classified in three risk groups according to combinations of gene expression levels, with times to progression of 10.13, 4.17 and 2.30 months (p = 0.001). Low BRCA1 expression was the only factor significantly associated with longer time to progression in 31 patients receiving cisplatin-based second-line therapy.<h4>Conclusions</h4>The mRNA expression of BRCA1, RRM1 and RRM2 is potentially a useful tool for selecting NSCLC patients for individualized chemotherapy and warrants further investigation in prospective studies.
format	article
author	Ioannis Boukovinas Chara Papadaki Pedro Mendez Miquel Taron Dimitris Mavroudis Anastasios Koutsopoulos Maria Sanchez-Ronco Jose Javier Sanchez Maria Trypaki Eustathios Staphopoulos Vassilis Georgoulias Rafael Rosell John Souglakos
author_facet	Ioannis Boukovinas Chara Papadaki Pedro Mendez Miquel Taron Dimitris Mavroudis Anastasios Koutsopoulos Maria Sanchez-Ronco Jose Javier Sanchez Maria Trypaki Eustathios Staphopoulos Vassilis Georgoulias Rafael Rosell John Souglakos
author_sort	Ioannis Boukovinas
title	Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.
title_short	Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.
title_full	Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.
title_fullStr	Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.
title_full_unstemmed	Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.
title_sort	tumor brca1, rrm1 and rrm2 mrna expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/2d8e5149519d416eb3ee0b6442ee0a97
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Tumor BRCA1, RRM1 and RRM2 mRNA expression levels and clinical response to first-line gemcitabine plus docetaxel in non-small-cell lung cancer patients.

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