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.
Highlights
Lung cancer is the leading cause of cancer-related death in the world because of its high morbidity and mortality
Expressed Proteins in Lung SCC Tumors and Paired Normal Lung Tissues—To screen differentially expressed proteins, tumors and their adjacent normal tissues from lung SCC patients were analyzed by 2D-DIGE
The nine spots identified as known contaminants and the eight spots with multiple proteins identification were excluded from further analysis
Summary
Samples—All of the tissue and blood specimens were collected from patients in the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences with informed consent and agreement. None of these patients received antineoplastic therapy prior to surgery. For 2D-DIGE, 12 pairs of fresh primary lung SCC tumors and their corresponding adjacent normal tissues were obtained during 2007–2008 (Table I). The independent 15 pairs of lung SCC samples were collected for RT-PCR and Western blot. 137 paraffinembedded lung tumors and paired adjacent normal lung tissues were randomly obtained from patients during 1999 –2001.
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