异柠檬酸脱氢酶
肺癌
生物标志物
癌症研究
腺癌
生物
IDH1
癌症
病理
医学
内科学
酶
基因
生物化学
突变
作者
Fengwei Tan,Ying Jiang,Nan Sun,Zhaoli Chen,Yongzhuang Lv,Kang Shao,Ning Li,Bin Qiu,Yibo Gao,Baozhong Li,Xiaogang Tan,Fang Jian Zhou,Zhen Wang,Da-Peng Ding,Jing Wang,Jian Sun,Jie Hang,Susheng Shi,Xiaoli Feng,Fuchu He,Jie He
标识
DOI:10.1074/mcp.m111.008821
摘要
Lung cancer is the leading cause of cancer-related death in the world. To explore tumor biomarkers for clinical application, two-dimensional fluorescence difference gel electrophoresis and subsequent MALDI-TOF/TOF mass spectrometry were performed to identify proteins differentially expressed in 12 pairs of lung squamous cell tumors and their corresponding normal tissues. A total of 28 nonredundant proteins were identified with significant alteration in lung tumors. The up-regulation of isocitrate dehydrogenase 1 (IDH1), superoxide dismutase 2, 14-3-3ε, and receptor of activated protein kinase C1 and the down-regulation of peroxiredoxin 2 in tumors were validated by RT-PCR and Western blot analysis in independent 15 pairs of samples. Increased IDH1 expression was further verified by the immunohistochemical study in extended 73 squamous cell carcinoma and 64 adenocarcinoma clinical samples. A correlation between IDH1 expression and poor overall survival of non-small cell lung cancer (NSCLC) patients was observed. Furthermore, ELISA analysis showed that the plasma level of IDH1 was significantly elevated in NSCLC patients compared with benign lung disease patients and healthy individuals. In addition, knockdown of IDH1 by RNA interference suppressed the proliferation of NSCLC cell line and decreased the growth of xenograft tumors in vivo. These observations suggested that IDH1, as a protein promoting tumor growth, could be used as a plasma biomarker for diagnosis and a histochemical biomarker for prognosis prediction of NSCLC.
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