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mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients
BACKGROUND: Metastatic 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 s...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203857/ https://www.ncbi.nlm.nih.gov/pubmed/21951562 http://dx.doi.org/10.1186/1479-5876-9-163 |
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author | Santarpia, Mariacarmela Magri, Ignacio Sanchez-Ronco, Maria Costa, Carlota Molina-Vila, Miguel Angel Gimenez-Capitan, Ana Bertran-Alamillo, Jordi Mayo, Clara Benlloch, Susana Viteri, Santiago Gasco, Amaya Mederos, Nuria Carcereny, Enric Taron, Miquel Rosell, Rafael |
author_facet | Santarpia, Mariacarmela Magri, Ignacio Sanchez-Ronco, Maria Costa, Carlota Molina-Vila, Miguel Angel Gimenez-Capitan, Ana Bertran-Alamillo, Jordi Mayo, Clara Benlloch, Susana Viteri, Santiago Gasco, Amaya Mederos, Nuria Carcereny, Enric Taron, Miquel Rosell, Rafael |
author_sort | Santarpia, Mariacarmela |
collection | PubMed |
description | BACKGROUND: Metastatic 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. METHODS: mRNA 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. RESULTS: BRCA1 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. CONCLUSIONS: The 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. |
format | Online Article Text |
id | pubmed-3203857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32038572011-10-29 mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients Santarpia, Mariacarmela Magri, Ignacio Sanchez-Ronco, Maria Costa, Carlota Molina-Vila, Miguel Angel Gimenez-Capitan, Ana Bertran-Alamillo, Jordi Mayo, Clara Benlloch, Susana Viteri, Santiago Gasco, Amaya Mederos, Nuria Carcereny, Enric Taron, Miquel Rosell, Rafael J Transl Med Research BACKGROUND: Metastatic 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. METHODS: mRNA 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. RESULTS: BRCA1 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. CONCLUSIONS: The 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. BioMed Central 2011-09-27 /pmc/articles/PMC3203857/ /pubmed/21951562 http://dx.doi.org/10.1186/1479-5876-9-163 Text en Copyright ©2011 Santarpia et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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. |
spellingShingle | Research Santarpia, Mariacarmela Magri, Ignacio Sanchez-Ronco, Maria Costa, Carlota Molina-Vila, Miguel Angel Gimenez-Capitan, Ana Bertran-Alamillo, Jordi Mayo, Clara Benlloch, Susana Viteri, Santiago Gasco, Amaya Mederos, Nuria Carcereny, Enric Taron, Miquel Rosell, Rafael mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients |
title | mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients |
title_full | mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients |
title_fullStr | mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients |
title_full_unstemmed | mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients |
title_short | mRNA expression levels and genetic status of genes involved in the EGFR and NF-κB pathways in metastatic non-small-cell lung cancer patients |
title_sort | mrna expression levels and genetic status of genes involved in the egfr and nf-κb pathways in metastatic non-small-cell lung cancer patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203857/ https://www.ncbi.nlm.nih.gov/pubmed/21951562 http://dx.doi.org/10.1186/1479-5876-9-163 |
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