期刊
THORACIC CANCER
卷 10, 期 4, 页码 715-727出版社
WILEY
DOI: 10.1111/1759-7714.12989
关键词
Gene co-expression network; microarray data; nilotinib; non-small cell lung cancer; non-smoking female
资金
- National Natural Science Foundation of China [81373311, 81173093, 30970643, 31300674, J1103518]
- Youth Science Foundation of West China Hospital of Stomatology [2017-3]
BackgroundAlthough cigarette smoking is considered one of the key risk factors for lung cancer, 15% of male patients and 53% of female patients with lung cancer are non-smokers. Metabolic changes are critical features of cancer. Therapeutic target identification from a metabolic perspective in non-small cell lung cancer (NSCLC) tissue of female non-smokers has long been ignored. ResultsBased on microarray data retrieved from Affymetrix expression arrays E-GEOD-19804, we found that the downregulated genes in non-smoking female NSCLC patients tended to participate in protein/amino acid and lipid metabolism, while upregulated genes were more involved in protein/amino acid and carbohydrate metabolism. Combining nutrient metabolic co-expression, protein-protein interaction network construction and overall survival assessment, we identified NR4A1 and TIE1 as potential therapeutic targets for NSCLC in female non-smokers. To accelerate the drug development for non-smoking female NSCLC patients, we identified nilotinib as a potential agonist targeting NR4A1 encoded protein by molecular docking and molecular dynamic stimulation. We also show that nilotinib inhibited proliferation and induced senescence of cells in non-smoking female NSCLC patients in vitro. ConclusionsThese results not only uncover nutrient metabolic characteristics in non-smoking female NSCLC patients, but also provide a new paradigm for identifying new targets and drugs for novel therapy for such patients.
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