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.
The work was supported by Chinese National Natural Science Foundation Grant 81101772; International Science and Technology Corporation and Exchange Project Grant 2010DFB30650 from the Chinese Ministry of Science and Technology; Key Technologies R & D Program Grant 2006BAI02A02; Chinese State Key Projects for Basic Research Grants 2011CB910601, 2011CB910700, 2010CB912700, and 2011CB505304; Chinese State Key Project Specialized for Infectious Diseases Grants 2008ZX10002-016 and 2009ZX10004-103; the National Key Technologies R & D Program for New Drugs Grant 2009ZX09301-002; International Scientific Collaboration Program Grants 2009DFB33070 and 2010DFA31260; and State Key Laboratory of Proteomics Grants SKLP-Y200901 and SKLP-O200901. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
