mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients

Journal of Translational Medicine

Research

Enric Carcereny¹  Maria Sanchez-Ronco²  Amaya Gasco³  Santiago Viteri³  Ana Gimenez-Capitan³  Jordi Bertran-Alamillo³  Nuria Mederos³  Miguel Angel Molina-Vila³  Ignacio Magri³  Clara Mayo³  Carlota Costa³  Susana Benlloch³  Rafael Rosell⁴  Miquel Taron⁴  Mariacarmela Santarpia⁵ 

[1] Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916, Badalona, Spain;Department of Health and Sociomedical Sciences, School of Medicine, University of Alcala de Henares, Crtra. Madrid-Barcelona, km. 33,600, 28801, Madrid, Spain;Pangaea Biotech, USP Dexeus University Institute, Sabino Arana 5- 19, 08028, Barcelona, Spain;Pangaea Biotech, USP Dexeus University Institute, Sabino Arana 5- 19, 08028, Barcelona, Spain;Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916, Badalona, Spain;Pangaea Biotech, USP Dexeus University Institute, Sabino Arana 5- 19, 08028, Barcelona, Spain;Medical Oncology Department, University of Messina, Via Consolare Valeria, 98125, Messina, Italy;

关键词: Epidermal Growth Factor Receptor;    Erlotinib;    Epidermal Growth Factor Receptor Mutation;    Epidermal Growth Factor Receptor Pathway;    Thiazolyl Blue Tetrazolium Bromide;   

DOI  :  10.1186/1479-5876-9-163

 received in 2011-05-06, accepted in 2011-09-27,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundMetastatic non-small-cell lung cancer (NSCLC) has a dismal prognosis. EGFR is overexpressed or mutated in a large proportion of cases. Downstream components of the EGFR pathway and crosstalk with the NF-κB pathway have not been examined at the clinical level. We explored the prognostic significance of the mRNA expression of nine genes in the EGFR and NF-κB pathways and of BRCA1 and RAP80 in patients in whom EGFR and K-ras gene status had previously been determined. In addition, NFKBIA and DUSP22 gene status was also determined.MethodsmRNA expression of the eleven genes was determined by QPCR in 60 metastatic NSCLC patients and in nine lung cancer cell lines. Exon 3 of NFKBIA and exon 6 of DUSP22 were analyzed by direct sequencing. Results were correlated with outcome to platinum-based chemotherapy in patients with wild-type EGFR and to erlotinib in those with EGFR mutations.ResultsBRCA1 mRNA expression was correlated with EZH2, AEG-1, Musashi-2, CYLD and TRAF6 expression. In patients with low levels of both BRCA1 and AEG-1, PFS was 13.02 months, compared to 5.4 months in those with high levels of both genes and 7.7 months for those with other combinations (P = 0.025). The multivariate analysis for PFS confirmed the prognostic role of high BRCA1/AEG-1 expression (HR, 3.1; P = 0.01). Neither NFKBIA nor DUSP22 mutations were found in any of the tumour samples or cell lines.ConclusionsThe present study provides a better understanding of the behaviour of metastatic NSCLC and identifies the combination of BRCA1 and AEG-1 expression as a potential prognostic model.

【 授权许可】

Unknown   
© Santarpia et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.