Expression of MRP1, BCRP, LRP and ERCC1 as prognostic factors in non-small cell lung cancer patients receiving postoperative cisplatin-based chemotherapy

Int J Biol Markers. 2009 Oct-Dec;24(4):230-7. doi: 10.1177/172460080902400403.

Abstract

The development of resistance to chemotherapy is one of the major obstacles in the treatment of non-small cell lung cancer (NSCLC). The purpose of this study was to investigate the 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 NSCLC patients receiving cisplatin-based adjuvant chemotherapy (cisplatin plus vinorelbine or gemcitabine) after tumor resection. We used semiquantitative reverse-transcription polymerase chain reaction to detect the expression of MRP1, BCRP, LRP and ERCC1 mRNA in surgical resection specimens of 60 patients with stage IB through IIIA NSCLC. The expression level of each gene was analyzed in relation to clinicopathological factors, tumor-free survival (TFS), and overall survival. The results showed that stage IIIA (p=0.011), N1 and N2 status (p=0.008), high expression of MRP1 (p=0.034) and LRP (p=0.018) were associated with shorter TFS. Stage IIIA (p=0.0105), N1 and N2 status (p=0.009), high expression of MRP1 (p=0.021) and ERCC1 (p=0.012) were related to a shorter overall survival. Cox multivariate analyses revealed that early stage (p=0.013 and p=0.024), negative lymph node status (p=0.006 and p=0.011), and low MRP1 expression (p=0.022 and p=0.035) were independent predictors of favorable TFS and overall survival, respectively. Additionally, ERCC1 (p=0.019) was an independent predictor of favorable overall survival.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics*
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / analysis
  • Vault Ribonucleoprotein Particles / genetics*

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
  • RNA, Messenger
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin
  • multidrug resistance-associated protein 1