摘要
目的通过对生信数据的挖掘来探究甲状腺功能亢进及甲状腺功能减退与老年骨质疏松之间的关联及治疗靶点。方法通过GEO数据库去挖掘老年骨质疏松症的差异表达基因,以及借助人类疾病数据库筛选骨质疏松、甲亢及甲减的靶基因。将上述基因整合映射后分别得出老年骨质疏松与甲亢、甲减的交集靶点基因。借助STRING数据库构建PPI网络,并且应用Cytoscape软件进行关键基因的筛选。通过R软件进行功能富集分析。结果老年骨质疏松分别与甲亢及甲减匹配映射得到67和126个交集靶点基因。PPI网络构建得出TNF、AKT1、ALB、CD4、IL2等关键基因可能与老年骨质疏松合并甲亢相关,并且受到Ⅰ型糖尿病、糖尿病并发症中的AGE-RAGE信号通路、人类T细胞白血病病毒Ⅰ型感染、移植物抗宿主病、EGFR酪氨酸激酶抑制剂耐药性等信号通路的调节;ALB、AKT1、TP53、TNF、CTNNB1等关键基因可能与老年骨质疏松合并甲减相关,并受到糖尿病并发症中的AGE-RAGE信号通路、T17细胞分化、人类T细胞白血病病毒Ⅰ型感染、癌症中的蛋白聚糖、人巨细胞病毒感染等信号通路调节。结论TNF、AKT1、ALB、CD4、IL2可能为老年骨质疏松和甲亢共病机制的基础,ALB、AKT1、TP53、TNF、CTNNB1可能为老年骨质疏松和甲减共病机制的基础。上述发现可能为进一步探究甲亢及甲减诱发老年骨质疏松发病机制和治疗机制提供新的思路。
Objective To explore the association and therapeutic targets among hyperthyroidism,hypothyroidism and senile osteoporosis based on bio-information data analysis.Methods The differentially expressed genes of senile osteoporosis were mined from the GEO database,and the target genes of osteoporosis,hyperthyroidism and hypothyroidism were screened from the human disease database.The intersection target genes of senile osteoporosis,hyperthyroidism and hypothyroidism in the elderly were obtained by integration mapping of the above genes.STRING database was used to construct PPI network,and Cytoscape software was used to screen hub genes.Functional enrichment analysis was carried out by R software.Results A total of 67and 126intersection target genes were obtained from the matched mapping of senile osteoporosis with hyperthyroidism and hypothyroidism,respectively.PPI network construction showed that TNF,AKT1,ALB,CD4,IL2may be hub genes related to senile osteoporosis combined with hyperthyroidism.They are regulated by Type I diabetes mellitus,AGE-RAGE signaling pathway in diabetic complications,Human T-cell leukemia virus 1infection,Graft-versus-host disease,EGFR tyrosine kinase inhibitor resistance,etc.ALB,AKT1,TP53,TNF,CTNNB1may be hub genes related to senile osteoporosis combined with hypothyroidism.They are regulated by AGE-RAGE signaling pathway in diabetic complications,Th17cell differentiation,Human T-cell leukemia virus 1infection,Proteoglycans in cancer,Human cytomegalovirus infection,etc.Conclusion TNF,AKT1,ALB,CD4 and IL2may be the basis for the comorbidity mechanism of senile osteoporosis and hyperthyroidism,and ALB,AKT1,TP53,TNF and CTNNB1may be the basis for the comorbidity mechanism of senile osteoporosis and hypothyroidism.The above findings may provide new ideas for further exploration of the pathogenesis and treatment mechanism of senile osteoporosis induced by hyperthyroidism and hypothyroidism.
作者
刘瑶
秦迪
刘东明
王岩
陈雷
黄丽红
LIU Yao;QIN Di;LIU Dongming;WANG Yan;CHEN Lei;HUANG Lihong(Department of Geriatrics,China-Japan Union Hospital of Jilin University,Changchun130033,China;Department of Endocrinology,Affiliated Hospital of Inner Mongolia University for Nationalities,Tongliao Inner Mongolia 028000,China;Science Research Center,China-Japan Union Hospital of Jilin University,Changchun 130033,China;Department of Emergency,Baicheng City Hospital,Baicheng Jilin 137000,China)
出处
《中国实验诊断学》
2024年第3期312-318,共7页
Chinese Journal of Laboratory Diagnosis