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
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / metabolism*
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Line, Tumor
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Cisplatin / pharmacology
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Cisplatin / therapeutic use
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Drug Resistance, Neoplasm / drug effects
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Electrophoresis, Gel, Two-Dimensional
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Female
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Humans
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Intracellular Signaling Peptides and Proteins / analysis
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Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
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Intracellular Signaling Peptides and Proteins / metabolism*
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Kaplan-Meier Estimate
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Lung Neoplasms / drug therapy
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Lung Neoplasms / metabolism*
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Lung Neoplasms / pathology
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Male
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Middle Aged
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Oncogene Proteins / analysis
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Oncogene Proteins / antagonists & inhibitors
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Oncogene Proteins / metabolism*
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Protein Deglycase DJ-1
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Proteomics*
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RNA Interference
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RNA, Small Interfering / metabolism
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Up-Regulation
Substances
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Antineoplastic Agents
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Intracellular Signaling Peptides and Proteins
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Oncogene Proteins
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RNA, Small Interfering
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PARK7 protein, human
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Protein Deglycase DJ-1
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Cisplatin