Proteomic analysis identified DJ-1 as a cisplatin resistant marker in non-small cell lung cancer

Int J Mol Sci. 2011;12(6):3489-99. doi: 10.3390/ijms12063489. Epub 2011 Jun 1.

Abstract

The aim of study is to identify cisplatin-resistance associated biomarkers for non-small cell lung cancers (NSCLC). We use two-dimensional electrophoresis (2-DE) combined with MALDI-TOF mass spectrometry to compare the proteome between lung cancer cell line A549 and its cisplatin-resistant subline A549/DDP. Nine cisplatin resistance-related proteins were identified, and DJ-1, one of the differently expressed proteins, was selected for further validation and evaluation. Immunohistochemical results demonstrated that high expression level of DJ-1 was associated with cisplatin resistance and a predictor for poor prognosis in 67 locally advanced NSCLC patients. Furthermore, in vitro results showed that silencing DJ-1 increased the proliferation inhibitory effect of cisplatin to A549/DDP cells. In conclusion, DJ-1 might play an important role in the resistibility to cisplatin, and it could also act as a novel candidate biomarker for predicting the response of NSCLC patients to cisplatin-based chemotherapy.

Keywords: DJ-1; cisplatin; non-small lung cancer; proteomics; resistance.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / drug effects
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Oncogene Proteins / analysis
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / metabolism*
  • Protein Deglycase DJ-1
  • Proteomics*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • RNA, Small Interfering
  • PARK7 protein, human
  • Protein Deglycase DJ-1
  • Cisplatin