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

Mariacarmela Santarpia, 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

Research output: Contribution to journalArticlepeer-review

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-B 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-B 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.

Original languageEnglish
Pages (from-to)163
Number of pages1
JournalJournal of Translational Medicine
DOIs
Publication statusAccepted/In press - Sep 27 2011

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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