利用药物重定位策略挖掘胃癌治疗药物  

Exploration of Therapeutic Drugs for Gastric Cancer Using Drug Repositioning Strategy

作　　者：齐鑫 荀德旭 冯舒琪 高娜 侯思宇 卢雨青 黄兰 陈佳佳 QI Xin;XUN Dexu;FENG Shuqi;GAO Na;HOU Siyu;LU Yuqing;HUANG Lan;CHEN Jiajia(School of Chemistry and Life Sciences,Suzhou University of Science and Technology Suzhou Jiangsu 215011)

机构地区：[1]苏州科技大学化学与生命科学学院,江苏苏州215011

出　　处：《电子科技大学学报》2023年第5期659-666,共8页Journal of University of Electronic Science and Technology of China

基　　金：国家自然科学基金面上项目(32270705)。

摘　　要：利用药物重定位和生物信息学的方法预测治疗胃癌的候选小分子药物及其潜在靶点,为胃癌的治疗提供新的思路。首先在胃癌数据集GSE54129、GSE26899和GSE65801中鉴定了203个差异表达基因,并利用关联图谱(connectivity map,CMap)分析筛选得到10种候选的小分子化合物。然后,通过对差异表达基因组成的蛋白质-蛋白质相互作用网络进行拓扑性质分析,鉴定TIMP1、PDGFRB、COL1A1等为枢纽基因。进一步,分子对接的结果显示,新鉴定的小分子药物左炔诺孕酮(levonorgestrel)与TIMP1具有较强的结合能力,结合能为-9.24 kcal/mol;已报道的胃癌药物西地尼布(cediranib)与靶点PDGFRB的结合能为-6.28 kcal/mol。另外,潜在靶点基因TIMP1和PDGFRB的表达模式、诊断和预后价值在胃癌数据集中得到了验证。This study aims to predict candidate small-molecule drugs for the treatment of Gastric Cancer(GC)and identify their potential targets by using drug repositioning and bioinformatics methods,providing new ideas for GC therapy.In this study,203 differentially expressed genes were first identified in GC datasets GSE54129,GSE26899 and GSE65801,and 10 candidate small-molecule compounds were screened by the Connectivity Map(CMap)analysis.Then,the topological properties of the protein-protein interaction network composed of differentially expressed genes were analyzed,and TIMP1,PDGFRB,COL1A1,etc.were identified as hub genes.Furthermore,molecular docking results showed that the newly identified small-molecule drug levonorgestrel had strong binding ability with TIMP1,and its binding energy was−9.24 kcal/mol;the binding energy of the reported GC drug Cediranib to the target PDGFRB was−6.28 kcal/mol.In addition,the expression patterns,diagnostic value and prognostic value of the potential target genes TIMP1 and PDGFRB were validated in the GC datasets.

关 键 词：关联图谱 药物重定位 胃癌 左炔诺孕酮 PDGFRB TIMP1 

分 类 号：TP391[自动化与计算机技术—计算机应用技术] R73[自动化与计算机技术—计算机科学与技术]