基质细胞评分的胃癌临床意义及胃复春胶囊干预机制

doi:10.3976/j.issn.1002-4026.2023.06.006

摘要/Abstract

摘要：

采用生物信息学方法分析基质细胞与胃癌的临床特征关联,预测胃复春胶囊的干预机制。从TCGA数据库下载胃癌活检数据,基于ESTIMATE计算基质细胞评分(stromal score,STRS)并以中位数为分组依据,分析STRS与患者临床信息关联并筛选DEGs(differentially expressed genes)作为潜在干预靶点。基于胃复春胶囊入血成分预测药物靶点,DEGs与药物靶点取交集并通过PPI网络及MCODE筛选核心子网络及基因,分析生存预后及不同分期表达。构建药味-入血成分-靶点网络筛选核心成分并进行ADMET预测及分子对接验证。交集靶点进行GO(gene ontology)、KEGG(Kyoto encyclopedia of genes and genomes)富集。结果表明:STRS与生存时间显著相关且随Stage及T分期显著升高,分析得DEGs 1 975个;胃复春胶囊入血成分75个,对应靶点663个,交集靶点107个;核心子网络4个,其中VCAM1、SERPINE1、TLR4、FGF1为核心靶点,SERPINE1、PDGFRB表达与生存时间相关极显著(P<0.01),VCAM1、NOX4、PDGFRB、ITGAL等在不同Stage分期表达差异极显著(P<0.01);异金雀花素B、香茶菜素O、蓝萼甲素等为核心成分,ADMET特性及核心靶点蛋白结合活性良好;GO富集于钙离子浓度调节、钙离子稳态等条目,KEGG富集于钙信号通路、神经活性配体-受体相互作用等通路。基质细胞与生存时间、分期密切相关,胃复春胶囊可能通过调控基质细胞发挥抑制肿瘤生长、转移及延缓耐药性等作用。

关键词: 基质细胞评分, 胃癌, 临床特征, 胃复春胶囊, 网络药理学

Abstract:

Bioinformatics methods were used to analyse the association between stromal cells and clinical characteristics of gastric cancer, and to predict the intervention mechanism of Weifuchun capsule. Gastric cancer biopsy data were downloaded from TCGA database, the stromal score (STRS) was calculated based on ESTIMATE, and the median was used as the basis for grouping, and the association between STRS and patients' clinical information was analysed, and the DEGs were screened as the potential intervention targets. Based on the blood components of Weifuchun capsule, we predicted the drug targets, intersected DEGs with drug targets, and screened the core sub-networks and genes through PPI network and MCODE, and analysed the expression of differentially expressed genes in terms of survival prognosis and different stages of the disease. The drug-taste-intake component-target network was constructed to screen the core components, and ADMET prediction and molecular docking validation were performed. The intersecting targets were enriched by GO and KEGG. The results showed that STRS was significantly correlated with survival time and increased significantly with Stage and T stage, and 1 975 DEGs were analysed; 75 components of Weifuchun capsule into the blood, corresponding to 663 targets, and 107 intersecting targets; and 4 core sub-networks, of which VCAM1, SERPINE1, TLR4, FGF1 were the core target, and SERPINE1, PDGFRB expression correlated with survival time was highly significant (P<0.01), and the differences in the expression of VCAM1, NOX4, PDGFRB, ITGAL, etc. in different Stage phases were highly significant (P<0.01); isocryptoxanthin B, geranylgeranyl O, and bluocalyx methylin were the core components, with good ADMET properties and core target protein binding activity. GO was enriched in calcium ion concentration regulation, calcium ion homeostasis and other entries. KEGG is enriched in calcium signalling pathway, neuroactive ligand-receptor interaction and other pathways. Stromal cells are closely related to survival time and stage, and Weifuchun capsule may inhibit tumour growth, metastasis and delay drug resistance by regulating stromal cells.

Key words: stromal cell score, gastric cancer, clinical features, Weifuchun capsules, network pharmacology

中图分类号:

R285

陈春, 祁大庆, 潘靖文. 基质细胞评分的胃癌临床意义及胃复春胶囊干预机制[J]. 山东科学, 2023, 36(6): 38-47.

CHEN Chun, QI Daqing, PAN Jingwen. Clinical significance of stromal cell score in gastric cancer and intervention with Weifuchun capsules[J]. Shandong Science, 2023, 36(6): 38-47.

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	脂水分配系数	极性表面积	溶解度		血脑屏障通透性		肠道吸收性	血浆蛋白结合率
	脂水分配系数	极性表面积	水溶性	水平	评分	水平	水平	评分	水平
Sudachinoid A	1.279	117.368	-4.408	2	—	4	0	-0.348	TRUE
橙桑黄酮F	2.801	58.931	-3.689	3	-0.221	2	0	-0.215	TRUE
熊果酸	5.397	60.832	-7.567	1	0.552	1	0	2.680	TRUE
槲皮素	0.927	126.793	-2.204	3	—	4	0	-5.093	FALSE
异橙黄酮	3.054	70.881	-4.282	2	-0.332	2	0	2.959	TRUE
去甲基川陈皮素	2.812	91.696	-4.002	2	-0.736	3	0	2.757	TRUE
橙皮素	2.357	97.607	-3.157	3	-0.970	3	0	-4.898	FALSE
香茶菜素U	1.136	120.323	-3.068	3	—	4	0	-3.715	FALSE
香茶菜素O	2.369	90.578	-4.243	2	-0.855	3	0	0.933	TRUE
异金雀花素B	3.894	67.861	-4.180	2	-0.024	2	0	1.098	TRUE
蓝萼甲素	1.914	76.232	-3.428	3	-0.769	3	0	-1.632	TRUE

靶点	核心入血成分	得分	靶点	核心入血成分	得分
SERPINE1 (1A7C)	香茶菜素U	127.490 0	FGF1 (1RGB)	香茶菜素O	84.677 2
	槲皮素	124.679 0		香茶菜素U	80.489 0
	香茶菜素O	123.846 0		去甲基川陈皮素	70.733 1
	橙皮素	116.495 0	TLR4 (2Z62)	香茶菜素U	109.480 0
	异橙黄酮	115.359 0		橙皮素	108.144 0
	异金雀花素B	115.265 0		香茶菜素O	100.347 0
	橙桑黄酮F	115.029 0		异金雀花素B	93.979 9
	蓝萼甲素	111.475 0		橙桑黄酮F	77.522 3
	去甲基川陈皮素	107.939 0		去甲基川陈皮素	76.464 3
FGF1 (1RGB)	熊果酸	91.647 7		异橙黄酮	72.309 3
	Sudachinoid A	70.469 2	VCAM1 (1VCA)	橙皮素	112.504 0
	橙皮素	108.080 0		香茶菜素O	105.116 0
	异橙黄酮	106.455 0		香茶菜素U	90.155 1
	异金雀花素B	88.554 2		异金雀花素B	84.955 7