Zeng Hua-Zong, Qu Yi-Qing, Zhang Wen-Jun, Xiu Bing, Deng An-Mei, Liang Ai-Bin
School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; E-Mail:
Int J Mol Sci. 2011;12(6):3489-99. doi: 10.3390/ijms12063489. Epub 2011 Jun 1.
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.
本研究的目的是鉴定非小细胞肺癌(NSCLC)中与顺铂耐药相关的生物标志物。我们使用二维电泳(2-DE)结合基质辅助激光解吸电离飞行时间质谱(MALDI-TOF)来比较肺癌细胞系A549与其顺铂耐药亚系A549/DDP之间的蛋白质组。鉴定出9种与顺铂耐药相关的蛋白质,并选择差异表达蛋白之一DJ-1进行进一步验证和评估。免疫组织化学结果表明,DJ-1的高表达水平与顺铂耐药相关,并且是67例局部晚期NSCLC患者预后不良的预测指标。此外,体外实验结果显示,沉默DJ-1可增强顺铂对A549/DDP细胞的增殖抑制作用。总之,DJ-1可能在顺铂耐药中起重要作用,并且还可作为预测NSCLC患者对基于顺铂化疗反应的新型候选生物标志物。