title: Prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 in early stage of non-small cell lung cancer.
abstract: BACKGROUND
  Nowadays, 40 % of early-stage NSCLC patients relapse in the 2 years following resection, suggesting a mis-staging in this group of patients who are not receiving adjuvant chemotherapy. Although different biomarkers, such as ERCC1, RRM1 and BRCA1 have been found to present prognostic value in advanced NSCLC patients, in early-stage NSCLC patients its relevance remains unclear. Moreover, SETDB1 has been recently proposed as a bona fide oncogene in lung tumourigenesis and related with metastasis. The aim of the present study was to analyze the prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 expression levels in NSCLC patients at stage I.
  
  
  METHODS
  ERCC1, RRM1, BRCA1 and SETDB1 expression at mRNA level was analyzed by real-time quantitative RT-PCR in fresh-frozen tumor and normal adjacent lung tissue samples from 64 stage I NSCLC patients. Later, significant association between gene expression levels, clinicopathological characteristics and patient's disease-free survival was assessed.
  
  
  RESULTS
  We did not find any statistically significant correlation between gene expression and gender, age, histological type or smoking status. Univariate followed by multivariate Cox analysis showed that higher levels of BRCA1 and SETDB1 expression were significantly associated with shorter disease-free survival in stage I NSCLC patients.
  
  
  CONCLUSIONS
  Our study finds that ERCC1 and RRM1 are not independent prognostic factors of recurrence in stage I NSCLC patients. By contrast, BRCA1 and SETDB1 stand out as the most significant prognostic markers in this group of patients, appearing as promising tools to predict tumor recurrence in early-stage NSCLC patients.
authors.affiliation: Servicio de Genética-Biología Molecular, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain. alafuente@hospital-ribera.com.
authors.forename: A
authors.initials: A
authors.lastname: Lafuente-Sanchis
authors.affiliation: Servicio de Genética-Biología Molecular, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain.
authors.forename: Á
authors.initials: Á
authors.lastname: Zúñiga
authors.affiliation: Servicio de Cirugía Torácica, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Galbis
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cremades
authors.affiliation: Servicio de Cirugía Torácica, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Estors
authors.affiliation: Servicio de Cirugía Torácica, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain.
authors.forename: N J
authors.initials: NJ
authors.lastname: Martínez-Hernández
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de València, Avda. Vicent Andrés Estellés, s/n, 46100, Burjassot, Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Carretero
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D018572:Disease-Free Survival; D004720:Endonucleases / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D011496:Protein Methyltransferases / Q000032:analysis / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C454062:SETDB1 protein, human; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: BRCA1; ERCC1; Gene expression; Lung cancer; Prognosis; RRM1; SETDB1