[复方利格列嗪治疗胃癌的网络药理学研究]。

Q3 Medicine

四川大学学报(医学版) Pub Date : 2024-09-20 DOI:10.12182/20240960503

Wei Xu, Zhaomin Deng, Xin Wang, Hao Jiang

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引用次数: 0

摘要

目的通过网络药理学分析，结合基因功能注释和临床数据分析，探讨复方四甲基吡嗪在胃癌治疗中的潜在作用和机制：方法：利用SwissTargetPrediction数据库筛选四甲基吡嗪的潜在药物作用位点，并结合OMIM和Genecard数据库获得胃癌相关靶点。通过交叉分析确定潜在的治疗靶点。随后，使用 ClusterProfiler 方法对交叉的下游靶点进行功能注释。此外，还利用癌症基因组图谱（TCGA）数据库获得了胃癌患者的原始数据，并进行了免疫浸润分析、miRNA分析、关键基因的转录调控分析、基因组富集分析（GSEA）、基因组变异分析（GSVA）、提名图模型构建和全基因组关联研究（GWAS）：结果：通过网络药理学筛选，我们发现了四甲基吡嗪作用于胃癌的 14 个潜在治疗靶点。功能注释显示，这些靶点主要参与激素代谢、药物代谢和信号转导通路。根据对数秩检验，在胃癌生存曲线的比较中，关键基因 ELANE 和 MPO 的表达有显著差异（PELANE 和 MPO 可能通过多种信号通路影响胃癌的发展）：本研究通过综合运用多种分析方法，发现利格列汀可通过调控ELANE和MPO的潜在靶点及相关信号通路对胃癌产生治疗作用。

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[Network Pharmacology Study of Compound Ligustrazine in Gastric Cancer Therapy].

Objective: To explore the potential role and mechanism of compound tetramethylpyrazine in gastric cancer therapy by using network pharmacology analysis combined with gene function annotation and clinical data analysis.

Methods: SwissTargetPrediction database was used to screen the potential drug action sites of compound tetramethylpyrazine, and the OMIM and Genecard databases were used in combination to obtain gastric cancer-related targets. Intersection analysis was performed to identify potential therapeutic targets. Subsequently, the method of ClusterProfiler was used to perform functional annotation of the downstream targets of intersection. In addition, The Cancer Genome Atlas (TCGA) database was used to obtain the original data of gastric cancer patients, and the immune infiltration analysis, miRNA analysis, transcriptional regulation analysis of key genes, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), nomogram model construction, and genome-wide association studies (GWAS) were performed.

Results: Through network pharmacological screening, we found 14 potential therapeutic targets through which tetramethylpyrazine acted on gastric cancer. Functional annotation showed that these targets were mainly involved in the pathways for hormone metabolism, drug metabolism, and signal transduction. Based on log rank test, the expression of the key genes, ELANE and MPO, showed significant difference in the comparison of gastric cancer survival curves (P<0.05), and were closely associated with immune cell infiltration. In addition, GSEA and GSVA results suggested that ELANE and MPO might influence the development of gastric cancer through multiple signaling pathways.

Conclusion: In this study, by using multiple analysis methods in an integrated way, we found that ligustrazine may have therapeutic effects on gastric cancer by regulating the potential targets of ELANE and MPO, as well as the relevant signaling pathways.

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来源期刊

四川大学学报(医学版) Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

0.70

自引率

0.00%

发文量

8695

期刊介绍： "Journal of Sichuan University (Medical Edition)" is a comprehensive medical academic journal sponsored by Sichuan University, a higher education institution directly under the Ministry of Education of the People's Republic of China. It was founded in 1959 and was originally named "Journal of Sichuan Medical College". In 1986, it was renamed "Journal of West China University of Medical Sciences". In 2003, it was renamed "Journal of Sichuan University (Medical Edition)" (bimonthly). "Journal of Sichuan University (Medical Edition)" is a Chinese core journal and a Chinese authoritative academic journal (RCCSE). It is included in the retrieval systems such as China Science and Technology Papers and Citation Database (CSTPCD), China Science Citation Database (CSCD) (core version), Peking University Library's "Overview of Chinese Core Journals", the U.S. "Index Medica" (IM/Medline), the U.S. "PubMed Central" (PMC), the U.S. "Biological Abstracts" (BA), the U.S. "Chemical Abstracts" (CA), the U.S. EBSCO, the Netherlands "Abstracts and Citation Database" (Scopus), the Japan Science and Technology Agency Database (JST), the Russian "Abstract Magazine", the Chinese Biomedical Literature CD-ROM Database (CBMdisc), the Chinese Biomedical Periodical Literature Database (CMCC), the China Academic Journal Network Full-text Database (CNKI), the Chinese Academic Journal (CD-ROM Edition), and the Wanfang Data-Digital Journal Group.