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Int J Exp Pathol. 2017 Apr;98(2):67-74. doi: 10.1111/iep.12221. Epub 2017 Jun 5.

Identification of DJ-1 as a contributor to multidrug resistance in human small-cell lung cancer using proteomic analysis.

Gao H1,2, Niu Y1,3, Li M1, Fang S1, Guo L1.

Author information

1
Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
2
Department of Pathology, Guangdong Women and Children Hospital, Guangzhou, China.
3
Department of Oncology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.

Abstract

Proteomic approaches have been proven to provide an important tool in identifying drug resistance-associated proteins. The aim of this study was to investigate the protein profiling of drug resistance-related proteins in small-cell lung cancer (SCLC) by proteomic analysis. The proteomic profiling was performed by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with MALDI-TOF-TOF of SCLC in the multidrug-resistant cell line H69AR and its parental cell line H69. A total of 11 proteins were identified to be >2-fold up-or downregulated between the two cell lines. DJ-1, one of the differently expressed proteins identified by proteomics, was further examined by immunohistochemistry staining in 116 cases of SCLC tissues. Immunohistochemical results demonstrated that DJ-1 was expressed in 51.7% (60/116) of SCLC. DJ-1 expression was correlated significantly with survival time of SCLC patients (P < 0.05), but not with other clinical parameters such as gender, age and clinical stage (P > 0.05). Downregulation of DJ-1 using DJ-1-siRNA in H69AR cells sensitized cancer cells to chemotherapeutic drugs through increasing drug-induced cell apoptosis accompanied with G0-G1 phase arrest. These findings suggest DJ-1 may serve as a potential biomarker for chemoresistance and prognostic factor for patients with SCLC.

KEYWORDS:

DJ-1; chemoresistance; proteomics; small-cell lung cancer

PMID:
28580701
PMCID:
PMC5485358
DOI:
10.1111/iep.12221
[Indexed for MEDLINE]
Free PMC Article

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