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六君子汤对一线化疗后晚期非小细胞肺癌患者的作用机制。

Mechanism underlying the effect of Liujunzi decoction on advanced-stage non-small cell lung cancer in patients after first-line chemotherapy.

机构信息

Department of Oncology, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Department of Orthopedics, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 20032, China.

出版信息

J Tradit Chin Med. 2022 Feb;42(1):108-115. doi: 10.19852/j.cnki.jtcm.2022.01.007.

Abstract

OBJECTIVE

To further clarify the anticancer mechanisms of Liujunzi decoction and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer (NSCLC) by re-analyzing differential gene expression profile of peripheral blood mononuclear cells (PBMCs) from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy.

METHODS

The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database. Differentially expressed genes (DEGs) were screened by paired sample t-test and the multiple ratio method. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed using the DAVID database. The protein-protein interaction (PPI) network was constructed using interaction gene library retrieval tools and Cytoscape software.

RESULTS

A total of 162 DEGs were identified, with 67 upregulated genes and 95 downregulated genes. The functional distribution of Gene Oncology (GO) genes showed that DEGs were mostly concentrated in extracellular regions, calcium ion binding, and transcriptase activity. KEGG pathway analysis showed that cytokine-cytokine receptor interactions were significantly enriched. PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree: IL2, PIWIL4, DICER1, PIWIL2, SAA1, XCL1, IL22RA1, ARHGAP11A, DCP1A, and GDNF. Among them, the central protein-coding gene with the highest node degree was IL2. In addition, the central protein-coding genes with high node degrees and high molecular complex detection (MCODE) scores were PIWIL4, DICER1, PIWIL2, and DCP1A, all of which are related to tumor development.

CONCLUSIONS

One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data. IL2, PIWIL4, DICER1, PIWIL2, and DCP1A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC. Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.

摘要

目的

通过重新分析接受一线化疗的 LiuJunZi 汤治疗的非小细胞肺癌(NSCLC)患者外周血单个核细胞(PBMC)的差异基因表达谱,进一步阐明 LiuJunZi 汤的抗癌机制,并为晚期 NSCLC 的治疗提供可能的靶点。

方法

从高通量基因表达数据库中检索到 PBMC 基因表达微阵列数据集 GSE61926。通过配对样本 t 检验和多重比法筛选差异表达基因(DEGs)。使用 DAVID 数据库进行基因本体论和京都基因与基因组百科全书(KEGG)通路分析。使用互作基因库检索工具和 Cytoscape 软件构建蛋白质-蛋白质相互作用(PPI)网络。

结果

共鉴定出 162 个 DEGs,其中 67 个上调基因和 95 个下调基因。GO 基因的功能分布表明,DEGs 主要集中在细胞外区域、钙离子结合和转录酶活性。KEGG 通路分析表明,细胞因子-细胞因子受体相互作用显著富集。PPI 网络分析筛选出具有最高节点度的前 10 个中央蛋白编码基因:IL2、PIWIL4、DICER1、PIWIL2、SAA1、XCL1、IL22RA1、ARHGAP11A、DCP1A 和 GDNF。其中,节点度最高的中央蛋白编码基因是 IL2。此外,节点度和高分子复合物检测(MCODE)评分高的中央蛋白编码基因有 PIWIL4、DICER1、PIWIL2 和 DCP1A,它们都与肿瘤的发生发展有关。

结论

通过重新分析 GSE61926 数据,筛选出一条与抗癌机制相关的信号通路和 10 个中央蛋白编码基因。IL2、PIWIL4、DICER1、PIWIL2 和 DCP1A 可能在 LiuJunZi 汤治疗 NSCLC 的机制中发挥重要作用。我们的研究结果表明,LiuJunZi 汤的抗癌机制可能与 RNA 基因沉默以及 piwi 相互作用 RNA 等小 RNA 的生物学过程有关。

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