基于Apriori和MIE算法分析真实世界乳腺癌术后巩固期用药规律及核心药物潜在作用机制

Analysis the real-world pattern of drug use and the potential mechanism of core drugs during the consolidation period after breast cancer surgery based on Apriori and MIE algorithm

目的通过Apriori和MIE算法,总结乳腺癌术后巩固期的用药规律及核心药物的潜在作用机制。方法筛选河南中医药大学第一附属医院乳腺病科2018年6月至2023年6月乳腺癌术后巩固期患者的中药方药构建数据库,运用Apriori、MIE算法及关联方法总结用药规律,选取置信度和支持度相对较高的核心药物,进行网络药理学分析。结果共收集609个处方,涉及中药203味,依频次排序前6位的中药为黄芪、附子、白术、淫羊藿、巴戟天及茯苓;中药功效类别以补虚药、清热解毒药、利水渗湿药为主;归经以肾经和脾经为主,四气以温为主,五味以甘为主;关联规则分析得到“巴戟天-淫羊藿”“黄芪-淫羊藿”“巴戟天-淫羊藿-黄芪”等配伍最常见。MIE分析得到“附子-白术”“淫羊藿-巴戟天”等强相关潜在药对。聚类分析得到类方,其基本的治疗原则为扶正益气,温补脾肾,兼以养心安神、疏肝健脾等。核心药物为“巴戟天-淫羊藿-黄芪”,对其进行网络药理分析,得到其主要活性成分为华良姜素、白桦脂酸、金圣草黄素等,核心靶点为TP53、SRC、HSP90AA1、PIK3CA、Akt1等,KEGG通路主要涉及癌症相关通路、PI3K-Akt信号通路等。结论乳腺癌术后巩固期的中医药治疗,以温补脾肾、扶正祛邪为主,辅以舒肝养心、化痰散结,临床用药多使用温阳益气之品,核心药物“巴戟天-淫羊藿-黄芪”的活性成分能够通过多种途径作用于多靶点从而抑制乳腺癌的复发及转移,研究结果为乳腺癌术后中医药治疗提供了临床指导和理论依据。

Objective To summarize the regularity of drug use in the consolidation period after breast cancer surgery through Apriori and MIE algorithm,and to discuss the potential mechanism of core drugs.Methods The traditional Chinese medicine prescriptions for breast cancer patients in the consolidation phase after surgery,from June 2018 to June 2023 at the Department of Breast Disease,the First Affiliated Hospital of Henan University of Chinese Medicine were screened and the database was constructed.The Apriori,MIE algorithm,and correlation method were employed to summarize the rule of medication.Core drugs with relatively high confidence and support were selected for network pharmacology analysis.Results A total of 609 prescriptions were collected,involving 203 Chinese herbs,with Astragali Radix,Aconiti Lateralis Radix Praeparata Atractylodis Macrocephalae Rhizoma,Epimedii Folium,Morindae Officinalis Radix,and Poria ranking among the top six in terms of frequency.The efficacy categories of the Chinese herbs mainly included tonifying deficiency drugs,clearing heat and removing toxicity drugs,and eliminating dampness and diuresis drugs.The meridians primarily targeted were the kidney channel and the spleen channel,with the nature mainly being warm,and the flavors predominantly sweet.Association rule analysis revealed that the most common combinations included“Morindae Officinalis Radix-Epimedii Folium”,“Astragali Radix-Epimedii Folium”,and“Morindae Officinalis Radix-Epimedii Folium-Astragali Radix”.MIE analysis yielded strong correlation potential drug pairs such as“Aconiti Lateralis Radix Praeparata-Atractylodis Macrocephalae Rhizoma”and“Morindae Officinalis Radix-Epimedii Folium-Astragali Radix”.Cluster analysis resulted in the identification of similar prescriptions,with the basic therapeutic principles being to reinforce the body and qi,warm and tonify the spleen and kidney,and also to nourish the heart and calm the mind,as well as to soothe the liver and strengthen the spleen.The core drug identified was“Morindae Officinalis Radix-Epimedii Folium-Astragali Radix”.Network pharmacological analysis of this core drug revealed that its main active components included paeoniflorin,betulinic acid,Jin Sheng Cao Huang Su,and so on.The key targets were TP53,SRC,HSP90AA1,PIK3CA,Akt1,and others.The KEGG pathway mainly involved cancer-related pathways,the PI3K-Akt signaling pathway,and others.Conclusion The traditional Chinese medicine treatment during the consolidation period after breast cancer surgery focuses on warming and tonifying the spleen and kidney,strengthening Uital qi to eliminate pathogenic factor.It is supplemented with the treatment of soothing the liver,nourishing the heart,dissipating phlegm and resolving masses.Clinical medication often utilizes herbs that warm the yang and vitalize qi.The active components of the core drug combination“Morindae Officinalis Radix-Epimedii Folium-Astragali Radix”can act on multiple targets through various pathways,thereby inhibiting the recurrence and metastasis of breast cancer.The research findings provide clinical guidance and a theoretical basis for traditional Chinese medicine treatment after breast cancer surgery.