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. 2011 Sep 27:9:163.
doi: 10.1186/1479-5876-9-163.

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

Mariacarmela Santarpia  1 , Ignacio Magri, Maria Sanchez-Ronco, Carlota Costa, Miguel Angel Molina-Vila, Ana Gimenez-Capitan, Jordi Bertran-Alamillo, Clara Mayo, Susana Benlloch, Santiago Viteri, Amaya Gasco, Nuria Mederos, Enric Carcereny, Miquel Taron, Rafael Rosell
Affiliations

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

Mariacarmela Santarpia et al. J Transl Med. .

Abstract

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.

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Figures

Figure 1
Figure 1
Inter-relationship and crosstalk among genes. The eleven genes analyzed in the present study are shown in pink. Red stars indicate mutations that were examined as part of routine clinical practice. Black stars indicate potential mutations that were examined as part of the present study.
Figure 2
Figure 2
PFS according to expression levels of BRCA1 and AEG-1. 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).
See this image and copyright information in PMC

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