title: XPG mRNA expression levels modulate prognosis in resected non-small-cell lung cancer in conjunction with BRCA1 and ERCC1 expression.
abstract: BACKGROUND
  Molecular markers can help identify patients with early-stage non-small-cell lung cancer (NSCLC) with a high risk of relapse. Excision repair cross-complementing 1 (ERCC1), Xeroderma pigmentosum group G (XPG), and breast cancer 1 (BRCA1) are involved in DNA damage repair, whereas ribonucleotide reductase M1 (RRM1) is implicated in DNA synthesis. Expression levels of these molecules might therefore have a prognostic role in lung cancer.
  
  
  METHODS
  We examined ERCC1, RRM1, XPG, and BRCA1 mRNA levels by real-time quantitative polymerase chain reaction in 54 patients with stage IB-IIB resected NSCLC. A strong correlation was observed between the 4 genes.
  
  
  RESULTS
  For patients with low BRCA1, regardless of XPG mRNA expression levels, disease-free survival (DFS) was not reached. For patients with intermediate/high BRCA1 and high XPG, DFS was 50.7 months. However, for patients with intermediate/high BRCA1 and low/intermediate XPG, DFS decreased to 16.3 months (P = .002). Similar differences were observed in overall survival, with median survival not reached for patients with low BRCA1, regardless of XPG levels, or for patients with intermediate/high BRCA1 and high XPG. Conversely, for patients with intermediate/high BRCA1 levels and low/intermediate XPG levels, median survival dropped to 25.5 months (P = .007).
  
  
  CONCLUSIONS
  BRCA1 and XPG were identified as independent prognostic factors for both median survival and DFS. High BRCA1 mRNA expression confers poor prognosis in early NSCLC, and the combination of high BRCA1 and low XPG expression still further increases the risk of shorter survival. These findings can help optimize the customization of adjuvant chemotherapy.
authors.affiliation: Azienda Ospedaliera Santa Maria, Terni, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bartolucci
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.forename: Jose Javier
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: Laia
authors.initials: L
authors.lastname: Perez-Roca
authors.forename: Imane
authors.initials: I
authors.lastname: Chaib
authors.forename: Francesco
authors.initials: F
authors.lastname: Puma
authors.forename: Raffaele
authors.initials: R
authors.lastname: Farabi
authors.forename: Pedro
authors.initials: P
authors.lastname: Mendez
authors.forename: Fausto
authors.initials: F
authors.lastname: Roila
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Okamoto
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C071447:ERCC1 protein, human