Integrated bioinformatics analysis to decipher molecular mechanism of compound Kushen injection for esophageal cancer by combining WGCNA with network pharmacology.

Abstract

Compound Kushen injection (CKI), a medicine in widespread clinical use in China, has proven therapeutic effects on cancer. However, few molecular mechanism analyses have been carried out. To address this problem, bioinformatics approaches combining weighted gene co-expression network analysis with network pharmacology methods were undertaken to elucidate the underlying molecular mechanisms of CKI in the treatment of esophageal cancer (ESCA). First, the key gene modules related to the clinical traits of ESCA were analysed by WCGNA. Based on the results, the hub genes related to CKI treatment for ESCA were explored through network pharmacology. Molecular docking simulation was performed to recognize the binding activity of hub genes with CKI compounds. The results showed that the potential hub targets, including EGFR, ErbB2, CCND1 and IGF1R, are therapeutic targets of CKI for the treatment of ESCA. Moreover, these targets were significantly enriched in many pathways related to cancer and signalling pathways, such as the PI3K-Akt signalling pathway and ErbB signalling pathway. In conclusion, this research partially highlighted the molecular mechanism of CKI in the treatment of ESCA, offering great potential in the identification of the effective compounds in CKI and biomarkers for ESCA treatment.

• Authors: Wei Zhou, Jiarui Wu, Jingyuan Zhang, Xinkui Liu, Siyu Guo, ShanShan Jia, Xiaomeng Zhang, Yingli Zhu, Miaomiao Wang
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 12745 (07 29 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32728182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• CCND1 protein, human
• Drugs, Chinese Herbal
• IGF1R protein, human
• Cyclin D1
• EGFR protein, human
• ERBB2 protein, human
• ErbB Receptors
• Receptor, ErbB-2
• Receptor, IGF Type 1
• kushen

Topics

• Algorithms
• Antineoplastic Agents (chemistry, pharmacology)
• Computational Biology (methods)
• Cyclin D1 (chemistry, metabolism)
• Databases, Genetic
• Drugs, Chinese Herbal (chemistry, pharmacology)
• ErbB Receptors (chemistry, metabolism)
• Esophageal Neoplasms (drug therapy, genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Regulatory Networks (drug effects)
• Humans
• Kaplan-Meier Estimate
• Models, Molecular
• Molecular Docking Simulation
• Receptor, ErbB-2 (chemistry, metabolism)
• Receptor, IGF Type 1 (chemistry, metabolism)
• Sequence Analysis, RNA