Association of EGFR mutant non-small cell lung cancer with TKI-related rash and prediction of potential traditional Chinese medicine based on network pharmacology
10.16781/j.CN31-2187/R.20230354
- VernacularTitle:基于网络药理学初探EGFR突变非小细胞肺癌与TKI相关皮疹的关联机制及潜在中药预测
- Author:
Lulu WU
1
;
Xiuwei LÜ
Author Information
1. 华中科技大学同济医学院附属武汉市中心医院中西医结合肿瘤科,武汉 430014
- Keywords:
non-small cell lung cancer;
epidermal growth factor receptor;
rash;
tyrosine kinase inhibitor;
traditional Chinese medicine
- From:
Academic Journal of Naval Medical University
2024;45(8):1005-1015
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the association of epidermal growth factor receptor(EGFR)mutant non-small cell lung cancer(NSCLC)with tyrosine kinase inhibitor(TKI)-related rash based on network pharmacology and to predict the potential traditional Chinese medicine.Methods Gene chip data of EGFR mutant NSCLC cell lines and normal fibroblasts before and after treatment with erlotinib,a TKI,were collected from Gene Expression Omnibus database.Differentially expressed genes were screened using limma package of R 4.3.2 software.Cross-over target genes were screened using venn package.The differentially expressed genes and cross-over target genes were analyzed using ClusterProfiler package.CoreMine Medical database was used to predict traditional Chinese medicine of the cross-over target genes,and the nature,flavour,and channel tropism were analyzed.The results were verified by molecular docking method.Results A total of 126 cross-over target genes were screened.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the differentially expressed genes and cross-over target genes were enriched in chromosome,spindle and other regions,and were involved in biological processes such as mitosis and DNA replication.These genes were also associated with signaling pathways including DNA replication,lysosomes,and cell cycle.Gene set enrichment analysis results showed that chemokine pathway and nucleotide-binding oligomerization domain-like receptor signaling pathway were activated in the NSCLC cells,and mammalian target of rapamycin signaling pathway and amino acid metabolic pathway were disturbed in the fibroblasts after treatment with erlotinib.CoreMine Medical database predicted that 354 kinds of traditional Chinese medicines were mainly classified as cold,warm and flat,bitter,pungent and sweet,belonging to stomach,lung and liver meridians.Taking Scutellaria baicalensis as an example,molecular docking analysis of experimentally validated target genes and their active components revealed strong binding interactions between the target genes and active components.Conclusion EGFR mutant NSCLC and TKI-related rash have homology in pathogenesis,both involving DNA replication and cell cycle,which provides traditional Chinese medicine medication instruction for patients with EGFR mutant NSCLC and TKI-related rash.
