Gene Expression of ERCC1 as a Novel Prognostic Marker in Advanced Bladder Cancer Patients Receiving Cisplatin-Based Chemotherapy

Ann Oncol. 2007 Mar;18(3):522-8. doi: 10.1093/annonc/mdl435. Epub 2007 Jan 17.

Abstract

Background: Customizing chemotherapy on the basis of chemosentitivity prediction may improve outcome in advanced bladder cancer patients. Since DNA damaging agents are the cornerstones of therapy, we hypothesized that levels of DNA repair genes could predict survival.

Patients and methods: Messenger RNA expression levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT-PCR in tumor DNA from 57 advanced and metastatic bladder cancer patients treated with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol). Levels were correlated with survival, time to disease progression and chemotherapy response.

Results: Median survival was significantly higher in patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow-up 19 months). A trend towards longer time to progression was observed in patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1 and caveolin-1, however, failed to predict the survival and a clear link with chemotherapy response could not be established. On multivariate analysis with pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for survival.

Conclusion: The results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • BRCA1 Protein / analysis
  • BRCA1 Protein / genetics
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Caveolin 1 / analysis
  • Caveolin 1 / genetics
  • Cisplatin / administration & dosage
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / genetics
  • Databases as Topic
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Endonucleases / analysis*
  • Endonucleases / genetics
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / analysis
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / genetics
  • Urinary Bladder Neoplasms / chemistry
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor
  • Caveolin 1
  • DNA-Binding Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Deoxycytidine
  • gemcitabine
  • RRM1 protein, human
  • ERCC1 protein, human
  • Endonucleases
  • Paclitaxel
  • Cisplatin