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Abstract
Objective Zao-Jiao-Ci (ZJC), a traditional Chinese medicine, is considered as a promising candidate to treat laryngeal squamous cell carcinoma (LSCC). However, the underlying molecular mechanism remains unclear. Methods Gene expression profiles of GSE36668 were available from the GEO database, and differentially expressed genes (DEGs) of LSCC were obtained by R package; subsequently, enrichment analysis on KEGG and GO of DEGs was performed. The active ingredients of ZJC were screened from the TCMSP database, and the matched candidate targets were obtained by PharmMapper. Furthermore, we constructed protein-protein interaction (PPI) networks of DEGs and candidate targets, respectively, and we screened the core network from the merged network through combining the two PPI networks using Cytoscape 3.7.2. The key targets derived from the core network were analyzed to find out the associated KEGG signal enrichment pathway. By the GEPIA online website, Kaplan–Meier analysis was used to complete the overall survival and disease-free survival of the selected genes in the core module. Results We identified 96 candidate targets of ZJC and 86 DEGs of LSCC, the latter including 50 upregulated genes and 36 downregulated genes. DEGs were obviously enriched in the following biological functions: extracellular structure organization, the extracellular matrix organization, and endodermal cell differentiation. The 60 key targets from the core network were enriched in the signal pathways including transcriptional misregulation cancer, cell cycle, and so on. We found that LSCC patients with high expression of HIST1H3J, HIST1H3F, and ITGA4 had worse overall survival, while higher expression of NTRK1, COPS5, HIST1H3A, and HIST1H3G had significantly worse disease-free survival. Conclusion It suggested that the interaction between ZJC and LSCC was related to the signal pathways of transcriptional misregulation cancer and cell cycle, revealing that it may be the mechanism of ZJC in the treatment of LSCC.
Highlights
Laryngeal squamous cell carcinoma (LSCC) is the most common malignancy of the larynx, and its clinical manifestations are hoarseness, stridor, dyspnea, and even dysphagia [1, 2]
An increasing number of studies confirmed that traditional Chinese medicine (TCM) including multiple ingredients and targets play a critical role in the treatment of cancer
PharmMapper server is the first webserver for potential drug targets identification through large-scale reverse pharmacophore mapping strategy [12]. e MOL structure of active ingredients provided by TCMSP was input into PharmMapper server to get the targets of the pharmacophore model. e first 15 targets sorted by the fit score were seemed as candidate targets of ZJC
Summary
Zao-Jiao-Ci (ZJC), a traditional Chinese medicine, is considered as a promising candidate to treat laryngeal squamous cell carcinoma (LSCC). Gene expression profiles of GSE36668 were available from the GEO database, and differentially expressed genes (DEGs) of LSCC were obtained by R package; subsequently, enrichment analysis on KEGG and GO of DEGs was performed. E key targets derived from the core network were analyzed to find out the associated KEGG signal enrichment pathway. We identified 96 candidate targets of ZJC and 86 DEGs of LSCC, the latter including 50 upregulated genes and 36 downregulated genes. E 60 key targets from the core network were enriched in the signal pathways including transcriptional misregulation cancer, cell cycle, and so on. It suggested that the interaction between ZJC and LSCC was related to the signal pathways of transcriptional misregulation cancer and cell cycle, revealing that it may be the mechanism of ZJC in the treatment of LSCC
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