Abstract
Purpose
Esophageal squamous cell carcinoma (ESCC), is a frequent digestive tract malignant carcinoma with a high fatality rate. Daphne altaica (D. altaica), a medicinal plant that is frequently employed in Kazakh traditional medicine, and which has traditionally been used to cure cancer and respiratory conditions, but research on the mechanism is lacking. Therefore, we examined and verified the hub genes and mechanism of D. altaica treating ESCC.
Methods
Active compounds and targets of D. altaica were screened by databases such as TCMSP, and ESCC targets were screened by databases such as GeneCards and constructed the compound-target network and PPI network. Meantime, data sets between tissues and adjacent non-cancerous tissues from GEO database (GSE100942, GPL570) were analyzed to obtain DEGs using the limma package in R. Hub genes were validated using data from the Kaplan–Meier plotter database, TIMER2.0 and GEPIA2 databases. Finally, AutoDock software was used to predict the binding sites through molecular docking.
Results
In total, 830 compound targets were obtained from TCMSP and other databases. In addition, 17,710 disease targets were acquired based on GeneCards and other databases. In addition, we constructed the compound-target network and PPI network. Then, 127 DEGs were observed (82 up-regulated and 45 down-regulated genes). Hub genes were screened including TOP2A, NUF2, CDKN2A, BCHE, and NEK2, and had been validated with the help of several publicly available databases. Finally, molecular docking results showed more stable binding between five hub genes and active compounds.
Conclusions
In the present study, five hub genes were screened and validated, and potential mechanisms of action were predicted, which could provide a theoretical understanding of the treatment of ESCC with D. altaica.
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Data availability
The datasets (GSE100942, GPL570) analysed during the current study are available in the [The Gene Expression Omnibus (GEO) database] repository, [https://www.ncbi.nlm.nih.gov/geo/].
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Acknowledgements
We are grateful to all the researchers who provided the data we used.
Funding
The authors appreciate financial support from the funding of Tianshan Talents-Youth Science and Technology Innovation Talents Training Program of Xinjiang Autonomous Region (2022TSYCCX0035); National Natural Science Foundation of China (81660696); "Fourteenth Five-Year Plan" Key Discipline Construction Project of Xinjiang Autonomous Region (2021); The key Laboratory of Xinjiang Autonomous Region (XJDX1713).
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SH, ZT, and WZ designed the study. SH, KA, MH performed bioinformatic analysis. JS, DD, and NN contributed to the conception of the study and drafted the manuscript. MN, NK, and NM contributed to the writing of the manuscript. All authors contributed to the article and approved the submitted version.
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Hailati, S., Talihati, Z., Abudurousuli, K. et al. Exploring the hub genes and mechanisms of Daphne altaica treating esophageal squamous cell carcinoma based on network pharmacology and bioinformatics analysis. J Cancer Res Clin Oncol 149, 8467–8481 (2023). https://doi.org/10.1007/s00432-023-04797-w
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DOI: https://doi.org/10.1007/s00432-023-04797-w