title: ERCC1 and BRAC1 mRNA expression levels in the primary tumor could predict the effectiveness of the second-line cisplatin-based chemotherapy in pretreated patients with metastatic non-small cell lung cancer.
abstract: BACKGROUND
  The potential predictive role of BRCA1 and ERCC1 expression levels in patients with metastatic non-small cell lung cancer (NSCLC) receiving second-line platinum-based chemotherapy was investigated.
  
  
  METHODS
  Real-time quantitative polymerase chain reaction after reverse transcription was used to assess the expression levels of BRCA1 and ERCC1 in 100 microdissected primary tumors from platinum-naive NSCLC patients treated with platinum-based chemotherapy in the second-line setting.
  
  
  RESULTS
  Low ERCC1 mRNA levels were significantly associated with higher response rate (p = 0.011), longer median progression-free survival (PFS; p = 0.029), and median overall survival (mOS; p = 0.001) after the initiation of the second-line treatment. Similarly, low BRCA1 expression level was significantly correlated with higher response rate (p = 0.022), longer PFS (p = 0.041), and mOS (p = 0.005). In addition, patients with low ERCC1 and BRCA1 mRNA experienced increased median PFS (p = 0.021) and mOS (p < 0.001) in comparison with those who had both genes upregulated. A multivariate analysis revealed that low ERCC1 and low BRCA1 expression levels were significantly associated with increased PFS (hazard ratio [HR]: 0.6; 95% confidence interval [CI]: 0.4-0.8; p = 0.029 and HR: 0.7; 95% CI: 0.6-0.9; p = 0.043, respectively) and OS (HR: 0.5; 95% CI: 0.3-0.7; p = 0.003 and HR: 0.7; 95% CI: 0.6-0.9; p = 0.038, respectively).
  
  
  CONCLUSIONS
  These results suggest that the ERCC1 and BRCA1 mRNA expression levels in the primary tumor at the time of diagnosis could be used for the prediction of platinum sensitivity in the treatment of NSCLC in the second-line setting. Cross-validation studies are warranted.
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Chara
authors.initials: C
authors.lastname: Papadaki
authors.forename: Maria
authors.initials: M
authors.lastname: Sfakianaki
authors.forename: Georgios
authors.initials: G
authors.lastname: Ioannidis
authors.forename: Eleni
authors.initials: E
authors.lastname: Lagoudaki
authors.forename: Maria
authors.initials: M
authors.lastname: Trypaki
authors.forename: Kostas
authors.initials: K
authors.lastname: Tryfonidis
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.forename: Efstathios
authors.initials: E
authors.lastname: Stathopoulos
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: John
authors.initials: J
authors.lastname: Souglakos
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000032:analysis*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin