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.
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.
authors.affiliation: Pangaea Biotech, USP Dexeus University Institute, Sabino Arana 5- 19, Barcelona, 08028, Spain.
authors.forename: Mariacarmela
authors.initials: M
authors.lastname: Santarpia
authors.forename: Ignacio
authors.initials: I
authors.lastname: Magri
authors.forename: Maria
authors.initials: M
authors.lastname: Sanchez-Ronco
authors.forename: Carlota
authors.initials: C
authors.lastname: Costa
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Molina-Vila
authors.forename: Ana
authors.initials: A
authors.lastname: Gimenez-Capitan
authors.forename: Jordi
authors.initials: J
authors.lastname: Bertran-Alamillo
authors.forename: Clara
authors.initials: C
authors.lastname: Mayo
authors.forename: Susana
authors.initials: S
authors.lastname: Benlloch
authors.forename: Santiago
authors.initials: S
authors.lastname: Viteri
authors.forename: Amaya
authors.initials: A
authors.lastname: Gasco
authors.forename: Nuria
authors.initials: N
authors.lastname: Mederos
authors.forename: Enric
authors.initials: E
authors.lastname: Carcereny
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D066246:ErbB Receptors