基于TCGA数据挖掘和分子对接技术探讨CCNB1高表达在肺腺癌中的意义及柴胡皂苷D的干预机制  

Exploring the significance of high expression of CCNB1 in lung adenocarcinoma and the intervention mechanism of Saikosaponin D based on TCGA data mining and molecular docking techniques

作　　者：黄瀚 吕晓东[1] 庞立健[2] HUANG Han;LYU Xiao-dong;PANG Li-jian(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China)

机构地区：[1]辽宁中医药大学,沈阳110847 [2]辽宁中医药大学附属医院,沈阳110032

出　　处：《中华中医药杂志》2022年第3期1714-1718,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81373579);辽宁省“兴辽英才计划”高水平创新团队项目(No.XLYC1808011);辽宁省科学技术计划项目(No.2019JH2/10300023)。

摘　　要：目的:基于TCGA数据挖掘及分子对接技术探究CCNB1高表达在肺腺癌中的意义及柴胡皂苷D的干预机制。方法:在TCGA数据库中获取肺腺癌相关数据,进行CCNB1基因的差异分析、配对差异分析、生存分析及其表达多重分析,发掘CCNB1基因表达与肺腺癌患者预后的相关性,并应用单因素、多因素COX回归分析CCNB1与肺腺癌患者的年龄、性别、临床分期、T分期、N分期等相关性,并判断其是否为独立预后因子;应用GSEA富集分析获取其发挥作用的机制及通路;采用分子对接技术将CCNB1与柴胡皂苷D进行对接,预测及判断其调控机制。结果:从TCGA数据库中获取肺腺癌组织535例、癌旁非癌样本59例。与癌旁非癌样本比较,肺腺癌组织中CCNB1基因表达显著升高(P<0.01),CCNB1基因低表达的生存率较高表达患者显著增加(P<0.01);男性肺腺癌患者CCNB1基因表达显著高于女性患者(P<0.01);Ⅱ、Ⅲ、Ⅳ期患者CCNB1基因表达显著高于Ⅰ期(P<0.01,P<0.05);T2期显著高于T1期(P<0.01);N1期、N2期显著高于N0期(P<0.01)。临床分期、T分期、N分期、CCNB1基因表达与总的生存期密切相关(P<0.01);临床分期和CCNB1基因表达可以作为独立的临床预后因子;CCNB1基因表达与细胞周期等密切相关。柴胡皂苷D与CCNB1存在结合靶点,最低结合能为-6.9 kcal/mol。结论:CCNB1基因是肺腺癌重要的临床预后因子,柴胡皂苷D可能通过调控CCNB1发挥抗肺腺癌的作用。Objective: To explore the significance of high expression of CCNB1 in lung adenocarcinoma and the intervention mechanism of Saikosaponin D based on TCGA data mining and molecular docking technology. Methods: The data of lung adenocarcinoma were collected from TCGA database, and CCNB1 gene expression was analyzed by differential analysis,paired difference analysis, survival analysis and expression multiple analysis. The correlation between CCNB1 gene expression and prognosis of lung adenocarcinoma patients was explored. The correlation between CCNB1 and lung adenocarcinoma patients’ age, gender, clinical stage, T stage, N stage was analyzed by univariate and multivariate COX regression analysis, and whether it was independent or not was analyzed. We used molecular docking technology to docking CCNB1 and Saikosaponin D to predict and judge its regulatory mechanism. Results: A total of 535 cases of lung adenocarcinoma and 59 cases of paracancerous non cancer samples were obtained from TCGA database. The CCNB1 gene expression in lung adenocarcinoma tissues was significantly higher(P<0.01) than that in non cancerous tissues, and the survival time of low expression of CCNB1 gene was significantly higher in high expression(P<0.01);expression of CCNB1 gene of male lung adenocarcinoma patients was significantly higher in female patients(P<0.01);CCNB1 gene expression in patients of stage Ⅱ, stage Ⅲ and stage Ⅳ was significantly higher than that in stage Ⅰ(P<0.01, P<0.05);T2 stage was higher than that in T1 stage(P<0.01). N1 stage was significantly higher than that in N0 stage(P<0.01);Clinical stage and CCNB1 gene expression were closely related to overall survival;multivariate COX regression analysis showed that clinical stage and CCNB1 gene expression could be used as independent clinical prognostic factors;CCNB1 gene expression was closely related to cell cycle. Saikosaponin D and CCNB1 had binding targets, and the lowest binding energy was-6.9 kcal/mol. Conclusion: CCNB1 gene is an important prognostic factor

关 键 词：肺腺癌 细胞周期蛋白B1 TCGA数据库 分子对接 柴胡皂苷D 

分 类 号：R273[医药卫生—中西医结合]