Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy

Lung Cancer. 2010 Jul;69(1):116-22. doi: 10.1016/j.lungcan.2009.09.013. Epub 2009 Oct 28.

Abstract

Purpose: The aim of this study was to investigate prognostic value of multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP) and excision repair cross-complementing 1 (ERCC1) in patients with locally advanced non-small cell lung cancer (NSCLC) who received neoadjuvant cisplatin-based chemotherapy.

Methods: Transbronchial biopsy (TBB) specimens from 46 patients with stage IIIA (N(2)) NSCLC were collected to determine the expression level of MRP1, BCRP, LRP and ERCC1 mRNA by semiquantitative RT-PCR. The expression level of each gene was analyzed in relation to histopathologic response to chemotherapy, and tumor-free survival (TFS) and overall survival.

Results: Patients with MRP1 or LRP low expression had a significantly better histopathologic response (P=0.032 and 0.006), and a significantly longer TFS (P=0.043 and 0.025) and overall survival (P=0.019 and 0.013) than those with MRP1 or LRP high expression. Patients with ERCC1 low expression had a significantly longer overall survival (P=0.007), but not TFS (P=0.094) than those with ERCC1 high expression. In multivariate analysis, LRP low expression was a significantly favorable factor for TFS (P=0.027), and LRP and ERCC1 were significantly favorable factors for overall survival (P=0.012 and 0.032).

Conclusion: Assessment of MRP1 and LRP mRNA expression in TBB specimens may predict histopathologic response and survival in locally advanced NSCLC patients who received neoadjuvant cisplatin-based chemotherapy. ERCC1 expression was predictive for overall survival.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease-Free Survival
  • Endonucleases / genetics
  • Endonucleases / metabolism*
  • Female
  • Humans
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Neoadjuvant Therapy
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Treatment Outcome
  • Vault Ribonucleoprotein Particles / genetics
  • Vault Ribonucleoprotein Particles / metabolism*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • DNA-Binding Proteins
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin
  • multidrug resistance-associated protein 1