title: Identification of isocitrate dehydrogenase 1 as a potential diagnostic and prognostic biomarker for non-small cell lung cancer by proteomic analysis.
abstract: 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.
authors: Department of Thoracic Surgery, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors: Fengwei
authors: F
authors: Tan
authors: Ying
authors: Y
authors: Jiang
authors: Nan
authors: N
authors: Sun
authors: Zhaoli
authors: Z
authors: Chen
authors: Yongzhuang
authors: Y
authors: Lv
authors: Kang
authors: K
authors: Shao
authors: Ning
authors: N
authors: Li
authors: Bin
authors: B
authors: Qiu
authors: Yibo
authors: Y
authors: Gao
authors: Baozhong
authors: B
authors: Li
authors: Xiaogang
authors: X
authors: Tan
authors: Fang
authors: F
authors: Zhou
authors: Zhen
authors: Z
authors: Wang
authors: Dapeng
authors: D
authors: Ding
authors: Jiwen
authors: J
authors: Wang
authors: Jian
authors: J
authors: Sun
authors: Jie
authors: J
authors: Hang
authors: Susheng
authors: S
authors: Shi
authors: Xiaoli
authors: X
authors: Feng
authors: Fuchu
authors: F
authors: He
authors: Jie
authors: J
authors: He
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome; D012333:RNA, Messenger; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human