BRCA1 mRNA expression as a predictive and prognostic marker in advanced esophageal squamous cell carcinoma treated with cisplatin- or docetaxel-based chemotherapy/chemoradiotherapy

PLoS One. 2013;8(1):e52589. doi: 10.1371/journal.pone.0052589. Epub 2013 Jan 9.

Abstract

Background: The molecular backgrounds that determine therapeutic effectiveness in esophageal cancer remain largely unknown. Breast cancer susceptibility gene 1 (BRCA1) expression has been found to switch the response to cisplatin- or paclitaxel-based chemotherapy. It remains unclear how variations in BRCA1 expression influence clinical outcomes in esophageal cancer.

Patients and methods: Quantitative real-time polymerase chain reaction (qPCR) was performed to examine BRCA1 mRNA expressions in paraffin-embedded specimens from 144 patients with advanced or metastatic esophageal squamous cell carcinoma who received cisplatin- or docetaxel-based first-line treatments.

Results: Low BRCA1 mRNA expression correlated with increased response rate (RR; P = 0.025 and 0.017, respectively) and median overall survival (mOS; P = 0.002 and P<0.001, respectively) in cisplatin-based chemotherapy or chemoradiotherapy group and also correlated with decreased RR (P = 0.017 and 0.024, respectively) and mOS (both P<0.001) in docetaxel-based chemotherapy or chemoradiotherapy group. Multivariate analysis revealed that low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29; 95%CI 0.12-0.71; P = 0.007) or chemoradiotherapy (HR 0.12; 95%CI 0.04-0.37; P<0.001) group and higher risk for mortality in docetaxel-based chemotherapy (HR 5.02; 95%CI 2.05-12.28; P<0.001) or chemoradiotherapy (HR 7.02; 95%CI 2.37-27.77; P<0.001) group.

Conclusions: BRCA1 mRNA expression could be used as a predictive and prognostic marker in esophageal cancer who underwent first-line cisplatin- or docetaxel-based treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • BRCA1 Protein / genetics*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy
  • Cisplatin / administration & dosage
  • Docetaxel
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Outcome Assessment, Health Care / statistics & numerical data
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Taxoids / administration & dosage

Substances

  • BRCA1 Protein
  • Biomarkers, Tumor
  • RNA, Messenger
  • Taxoids
  • Docetaxel
  • Cisplatin

Grants and funding

This work was supported in part by Science Developing Foundation of Nanjing Medical University (09NJMUM063 to Y.G.) and Science Developing Foundation of Huaian Government (HAS2011028 to X.F.C.). The funders had no role in study design, data collection and analysis.