基于泛癌Bulk RNA-Seq探索不同五运六气气化体质人群肿瘤的生物学特征
Exploration of cancer biological characteristics in people with different five movements and six climates constitution based on pan-cancer Bulk RNA-Seq
唐心浩 1储博文 2李辰天一 3王映菲 3夏仲卉 3李梓墨 4田心语 3王聪颖 5陈琪 5郝帅 6陶维 7王建明 8吴勉华 3郑晓红9
作者信息
- 1. 南京中医药大学 第一临床医学院,江苏 南京 210023;江苏省老龄事业发展研究会 老年康养与中医药研究专委会,江苏 南京 210024
- 2. 皖南医学院 微生物与免疫教研室,安徽 芜湖 241002;国家癌症中心 分子肿瘤学国家重点实验室,北京 100021
- 3. 南京中医药大学 第一临床医学院,江苏 南京 210023
- 4. 江汉大学 医学部 药学系,湖北武汉 430056
- 5. 南京中医药大学 中医药文献研究所,江苏 南京 210023
- 6. 南京大学 医学院附属金陵医院,江苏 南京 210000
- 7. 南京中医药大学 附属南京中医院,江苏 南京 210022
- 8. 南京中医药大学 太仓附属医院,江苏 太仓 215400
- 9. 江苏省老龄事业发展研究会 老年康养与中医药研究专委会,江苏 南京 210024;南京中医药大学 中医药文献研究所,江苏 南京 210023;南京中医药大学 中医学院,江苏 南京 210023
- 折叠
摘要
中医五运六气气化理论认为先天气化体质是决定后天疾病发病特征的关键因素.既往研究表明,五运六气气化体质(以下简称体质)特征与多种肿瘤的发生发展密切相关,基于中医五运六气气化理论的肿瘤分型可反映肿瘤人群的预后风险.五运六气气化理论具有较高的应用于指导肿瘤精准医疗策略构建的潜力,然而目前尚未有学者对五运六气气化理论指导肿瘤分子分型与精准医疗策略构建进行研究.为揭示不同体质肿瘤人群的生物学特征差异,筛选适用于各体质人群的潜在抗肿瘤药物,助力构建源自中医原创思维的肿瘤中西医协同精准医疗策略.该研究从UCSC Xena获得了泛癌Bulk RNA-Seq数据,从英国生物库获得了GWAS队列数据,从eQTLGen和GTEx V8 获得了cis-eQTLs数据.研究基于泛癌Bulk RNA-Seq,利用机器学习法筛选各体质人群的特征表达基因,利用生物信息学手段探索各体质人群的生物学特征差异,利用孟德尔随机化进行药物靶点筛选,通过分子对接筛选适用于各体质人群的潜在抗肿瘤中药单体,并预测中药单体成药性.结果显示,泛癌队列中不同体质人群在无进展间隔期、生物学功能、免疫细胞丰度、肿瘤药物敏感性、免疫疗法响应程度等方面存在显著差异,提示五运六气气化理论可应用于指导肿瘤分子分型与肿瘤精准医疗策略制定.泛癌队列中不同体质人群的生物学功能特征,一定程度上诠释了五运六气气化理论等中医理论的生物学内涵,并为中医肿瘤临床治疗提供新思路.DMKN等5 个特征基因被作为虚拟药物筛选受体,通过分子对接与类药性预测后筛选得到 17-beta-estradiol、serotonine、trans-resveratrol、leinoleic acid等潜在抗肿瘤药物.以转录组测序为代表的组学技术将是揭示中医理论科学内涵的有力工具.在各类肿瘤人群中阐释不同体质的多组学特征,是五运六气气化理论应用于肿瘤分子分型与肿瘤精准医疗策略制定的基础.
Abstract
According to the theory of five movements and six climates,the innate constitution plays a crucial role in determining the underlying pathological mechanisms of diseases later in life.Previous studies have demonstrated a close association between the constitution,as defined by the theory of five movements and six climates,and the development of various types of tumors.Furthermore,the tumor subtype determined by the constitution has prognostic implications.This highlights the potential of utilizing the five movements and six climates theory to guide the implementation of precision medicine strategies in the field of oncology.However,no research has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precision medicine strategies.The objective of this research is to uncover the biological characteristics of each constitution within a pan-cancer cohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types.By doing so,we aim to contribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chinese medicine(TCM).In this study,we obtained pan-cancer Bulk RNA-Seq data from UCSC Xena,GWAS cohort data from the UK Biobank,and cis-eQTLs data from eQTLGen and GTEx V8.We employed machine learning methods to screen for hub genes associated with each constitution.Subsequently,we utilized bioinformatics tools to explore the biological characteristics of each constitution defined by the theory of five movements and six climates.Further,potential anti-tumor drugs suitable for patients with different constitutional types were identified through mendelian randomization,molecular docking,and drug-like prediction techniques.Within the pan-cancer cohort,significant differences were observed among different constitutions in terms of progression-free interval,biological functions,immune cell abundance,tumor drug sensitivity,and immunotherapy response.These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies.Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicine theories,offering a fresh perspective towards clinical cancer treatment.Through molecular docking and drug-like prediction,several potential anti-tumor drugs such as 17-beta-estradiol,serotonin,trans-resveratrol,and linoleic acid were identified.Overall,the utilization of multi-omics approaches provides a powerful tool to unravel the scientific foundations of TCM theories.The elucidation of the multi-omics features associated with each constitution in tumors serves as the basis for applying the five movements and six climates theory to tumor molecular classification and the development of precision medicine strategies.
关键词
泛癌/五运六气/肿瘤分子分型/中西医结合/药物虚拟筛选Key words
pan-cancer/five movements and six climates/tumour molecular classification/integrated Chinese and western medi-cine/drug virtual screening引用本文复制引用
基金项目
国家社会科学基金重大项目(18ZDA322)
江苏省医学科研重点项目(ZD2022068)
江苏省中医药科技发展计划委托研究项目(2022WTZX02)
苏州市科技发展计划指导性项目(SKYD2023206)
国家级大学生创新训练项目(202210315128Z)
南京中医药大学"罗林秀杯"大学生创新培育项目()
南京中医药大学中医药人工智能"揭榜挂帅"项目()
出版年
2024
NETL
NSTL
万方数据