Prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 in early stage of non-small cell lung cancer

Clin Transl Oncol. 2016 Aug;18(8):798-804. doi: 10.1007/s12094-015-1440-6. Epub 2015 Nov 5.

Abstract

Introduction: 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.

Patients and 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.

Conclusion: 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.

Keywords: BRCA1; ERCC1; Gene expression; Lung cancer; Prognosis; RRM1; SETDB1.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / analysis
  • BRCA1 Protein / biosynthesis
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / biosynthesis
  • Disease-Free Survival
  • Endonucleases / analysis
  • Endonucleases / biosynthesis
  • Female
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology*
  • Prognosis
  • Proportional Hazards Models
  • Protein Methyltransferases / analysis
  • Protein Methyltransferases / biosynthesis
  • Real-Time Polymerase Chain Reaction
  • Ribonucleoside Diphosphate Reductase
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / biosynthesis

Substances

  • BRCA1 Protein
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • SETDB1 protein, human
  • ERCC1 protein, human
  • Endonucleases