Abstract
Non-small cell lung cancer (NSCLC) is the most common type in lung cancer in the world, and it severely threatens the life of patients. Resveratrol has been reported to inhibit cancer. However, mechanisms of resveratrol inhibiting NSCLC were unclear. The aim of this study was to identify differentially expressed genes (DEGs) of NSCLC treated with resveratrol and reveal the potential targets of resveratrol in NSCLC. We obtained mRNA expression profiles of two datasets from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) and 271 DEGs were selected for further analysis. Data from STRING shown that 177 nodes and 342 edges were in the protein-protein interaction (PPI) network, and 10 hub genes (ANPEP, CD69, ITGAL, PECAM1, PTPRC, CD34, ITGA1, CCL2, SOX2, and EGFR) were identified by Cytoscape plus-in cytoHubba. Survival analysis revealed that NSCLC patients showing low expression of PECAM1, ANPEP, CD69, ITGAL, and PTPRC were associated with worse overall survival (OS) (P < 0.05), and high expression of SOX2 and EGFR was associated with worse OS for NSCLC patients (P < 0.05). Overall, we identified ANPEP, CD69, ITGAL, and PTPRC as potential candidate genes which were main effects of resveratrol on the treatment of NSCLC. ANPEP, ITGAL, CD69, and PTPRC are all clusters of differentiation (CD) antigens, might be the targets of resveratrol. The bioinformatic results suggested that the inhibitory effect of resveratrol on lung cancer may be related to the immune signaling pathway. Further studies are needed to validate these findings and to explore their functional mechanisms.
Highlights
Lung cancer has the second highest incidence and the highest mortality in the world [1]
47 genes were found down-regulated in Non-small-cell lung cancer (NSCLC), while decreased by resveratrol, too (Figure 1E). 56 genes were increased in NSCLC and the expressions were even higher after treatment with resveratrol (Figure 1F)
A total of 271 differentially expressed genes (DEGs) were identified, including 135 genes were increased by resveratrol treatment and down-regulated in NSCLC, 33 genes were reduced by resveratrol and up-regulated in NSCLC. 47 genes were found decreased by resveratrol and down-regulated in NSCLC, 56 genes were increased in NSCLC and the expressions were even higher after resveratrol treatment
Summary
Lung cancer has the second highest incidence and the highest mortality in the world (https://www.iarc.fr/faq/ latest-global-cancer-data-2020-qa/) [1]. It is imperative that searching for effective targets for the diagnostic of NSCLC. The potential of resveratrol on cancer treatment has been reported and a large number of studies have confirmed that resveratrol has a good inhibitory effect on various tumors including NSCLC [6]. Wang et al found that www.aging-us.com resveratrol might inhibit proliferation but induce apoptosis and autophagy via inhibiting Akt/mTOR pathway and activating p38-MAPK pathway in A549 and H1299 NSCLC cells [7]. Resveratrol inhibits proliferation, migration, invasion and promotes apoptosis via inhibiting the messenger RNA (mRNA) and protein expression of signal transducer and activator of transcription 3 (STAT3) in A549 cells [8]. Reports about new targets of resveratrol in NSCLC are still few and further investigations are urgently needed
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