Metabolic gene NR4A1 as a potential therapeutic target for non‐smoking female non‐small cell lung cancer patients

Abstract

Background Although 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. Results Based 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. Conclusions These 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.

Keywords

• Gene co‐expression network
• microarray data
• nilotinib
• non‐small cell lung cancer
• non‐smoking female