title: Correlation of BRCA1, TXR1 and TSP1 mRNA expression with treatment outcome to docetaxel-based first-line chemotherapy in patients with advanced/metastatic non-small-cell lung cancer.
abstract: BACKGROUND
  We explored the predictive significance of BRCA1, TXR1 and TSP1 expression in non-small-cell lung cancer (NSCLC) patients treated with docetaxel in association with cisplatin or gemcitabine.
  
  
  METHODS
  To analyse BRCA1, TXR1 and TSP1 mRNA expression from microdissected primary tumours of 131 patients with stage IIIB (wet) and IV NSCLC, RT-qPCR was used.
  
  
  RESULTS
  The mRNA levels of TXR1/TSP1 were inversely correlated (Spearman's test: -0.37; P=0.001). Low TXR1 mRNA levels were associated with higher response rate (RR; P=0.018), longer median progression-free survival (PFS; P=0.029) and median overall survival (mOS P=0.003), whereas high TSP1 expression was correlated with higher RR (P=0.035), longer PFS (P<0.001) and mOS (P<0.001). Higher BRCA1 mRNA expression was associated with higher RR (P=0.028) and increased PFS (P=0.021), but not mOS (P=0.4). Multivariate analysis demonstrated that low TXR1/high TSP1 expression was an independent factor for increased PFS (HR 0.49; 95% CI 0.32-0.76; P<0.001) and mOS (HR 0.37; 95% CI 0.2-0.58; P<0.001), whereas high BRCA1 expression was correlated with increased PFS (HR 0.53; 95% CI 0.37-0.78; P=0.001).
  
  
  CONCLUSIONS
  These data indicate that TXR1/TSP1 and BRCA1 expression could be used for the prediction of taxanes' resistance in the treatment of NSCLC.
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Papadaki
authors.forename: E
authors.initials: E
authors.lastname: Tsaroucha
authors.forename: L
authors.initials: L
authors.lastname: Kaklamanis
authors.forename: E
authors.initials: E
authors.lastname: Lagoudaki
authors.forename: M
authors.initials: M
authors.lastname: Trypaki
authors.forename: K
authors.initials: K
authors.lastname: Tryfonidis
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.forename: E
authors.initials: E
authors.lastname: Stathopoulos
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: J
authors.initials: J
authors.lastname: Souglakos
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D000077143:Docetaxel; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C513606:PRR13 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; C481348:SPZ1 protein, human; D043823:Taxoids; D000077143:Docetaxel