文献类型：期刊文献

中文题名：构建P53介导的线粒体动力学失调预后模型及黄芪甲苷在乳腺癌中的抗肿瘤机制

英文题名：Constructionof a prognosis model of P53-mediated mitochondrial dynamics disorder and the anti-tumor mechanism of astragaloside in breast cancer

作者：张忠文[1];张浩令[4];赵瑞[2];齐雅茜[2];杨钰婷[3];白金霞[3];王薇[3];张稼悦[5];王芙蓉[6]

第一作者：张忠文

机构：[1]甘肃中医药大学公共卫生学院,甘肃兰州730000;[2]甘肃中医药大学中医临床学院,甘肃兰州730000;[3]甘肃中医药大学针灸推拿学院,甘肃兰州730000;[4]马来西亚理科大学高级医学与牙科研究所,马来西亚槟城13200;[5]华南农业大学林学与风景园林学院,广东广州510000;[6]兰州大学第二医院病理科,甘肃兰州730030

第一机构：甘肃中医药大学公共卫生学院

年份：2023

卷号：49

期号：12

起止页码：22

中文期刊名：兰州大学学报（医学版）

外文期刊名：Journal of Lanzhou University（Medical Sciences）

收录：CSTPCD

基金：甘肃省高等学校创新基金资助项目(2023A-088);甘肃省自然科学基金资助项目(22JR5RA582,21JR1RA267);甘肃省科技计划项目任务书(重点研究发展计划)资助项目(23YFWA0005);甘肃省中医药研究中心专项开放课题资助项目(zyzx-2020-zx10);甘肃省教育科技创新资助项目(2022A-067)。

语种：中文

中文关键词：乳腺癌;肿瘤蛋白53;线粒体动力学;黄芪甲苷;干预机制;富集分析

外文关键词：breast cancer;tumor protein 53;intervention mechanism;enrichment analysis

摘要：目的 旨在通过构建抗肿瘤蛋白53(P53)可介导线粒体动力学失调相关mRNA在乳腺癌(BC)中的预后模型,探索其在BC中的预后价值及黄芪甲苷(AS-IV)在BC预后治疗中的潜在意义。方法 通过NCBIGENE数据库获得P53介导线粒体动力学相关mRNA,从癌症基因组图谱数据集获得BC的RNAseq数据和相应的临床信息,并筛选数据。使用“survival”包通过单变量Cox回归和Log-rank检验P53介导线粒体动力学在癌症基因组图谱中的预后价值mRNA。使用“glmnet”包应用LASSO-Cox回归分析构建预后模型。通过使用“ggcorrplot”包,评估风险组与免疫浸润人群间Pearson相关性分析。风险组基因进行京都基因与基因组百科全书通路富集分析。通过分子对接评估AS-IV与预后模型mRNA的结合能力。结果 P53介导线粒体动力学相关的XIAP、VDAC1、UNG、SOCS3、SIRT4、SERPINB5、SERPINA1、S100B、RB1、NOS2、NFKBIA、NDRG1、IRF1、IGF1R、HDAC2、FOXO3、FLT3、CASP918个mRNA构建了BC的预后模型,其中8个为高风险基因,10个为低风险基因。与低风险组患者相比,高风险组患者的总生存期更短(P<0.001);对接结果推断高风险评分蛋白受体XIAP、VDAC1、SIRT4、RB1、NOS2、NFKBIA与配体小分子AS-IV具有强烈的结合活性,潜在生物活性较高。结论 构建了18个mRNA-P53介导线粒体动力学相关的BC预后模型,并且可以作为一个独立的预后因素。AS-IV是通过作用于XIAP、VDAC1、SIRT4、RB1、NOS2、NFKBIAmRNA治疗BC潜在药物。
Objective To explore the prognostic value of tumor protein 53(P53)in breast cancer(BC)and the potential significance of astragaloside IV(AS-IV)in the prognostic treatment of BC by contructing a prognos-tic model of mRNA associated with mitochondrial dynamic dysregulation in BC.Methods P53-mediated mitochondrial dynamics mRNA was obtained from the NCBI GENE database,RNAseq data of BC and corre-sponding clinical information were obtained from cancer genome Atlas dataset,and the data were screened.The survival package was used to examine the prognostic value of P53-mediated mitochondrial dynamics in cancer genome mapping mRNA by univariate Cox regression and Log-rank.A prognostic model was con-structed by LASSO-Cox regression analysis using the"glmnet"package.Pearson correlation analysis between the risk group and the immunoinfiltrated population was evaluated using the"ggcorrplot"package.Risk group genes were analyzed by the Kyoto Encyclopedia of Genes and Genomes pathway enrichment.The ability of AS-IV to bind to the prognostic model mRNA was evaluated by molecular docking.Result P53-mediated mitochondrial dynamics related XIAP,VDAC1,UNG,SOCS3,SIRT4,SERPINB5,SERPINA1,S100B,RB1,NOS2,NFKBIA,NDRG1,IRF1,IGF1R,HDAC2,FOXO3,FLT3 and CASP9.The prognostic model of BC was successfully constructed with 18 mRNAs,of which 8 were high-risk genes and 10 low-risk genes.The overall survival was significantly shorter in the high-risk than in the low-risk group(P<0.001).The docking results suggested that high-risk scoring protein receptors XIAP,VDAC1,SIRT4,RB1,NOS2 and NFKBIA dem-onstrated strong binding activity with the small ligand molecule AS-IV,and possessed high potential biologi-cal activity.Conclusion 18 mRNA-P53 mediated mitochondrial dynamics related BC prognostic models were constructed,which can be used as an independent prognostic factor.AS-IV is a potential drug for the treatment of BC by acting on XIAP,VDAC1,SIRT4,RB1,NOS2,NFKBIA and mRNA.