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基于网络药理学和生物信息学分析探讨葛根素治疗子宫内膜癌的作用机制及实验验证。

Exploring the mechanism and experimental verification of puerarin in the treatment of endometrial carcinoma based on network pharmacology and bioinformatics analysis.

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, 250014, Shandong, China.

Shandong University Cheeloo College of Medicine Laboratory of Basic Medical Sciences, Jinan, 250014, Shandong, China.

出版信息

BMC Complement Med Ther. 2022 Jun 7;22(1):150. doi: 10.1186/s12906-022-03623-z.

Abstract

Endometrial carcinoma is one of the two cancers with rising mortality and morbidity in recent years. In the light of many controversies about its treatment, it is urgent to construct a new prognostic model and to find out new therapeutic directions. As a small drug molecule widely used in clinical treatment and experimental research in China, puerarin has recently been proven to have obvious anti-cancer effects in multiple cancer cells. In this study, bioinformatics analysis and experimental validation were used to explore the potential mechanism of puerarin for endometrial carcinoma and construct a prognostic model. A total of 22 drug-related differential genes were found by constructing a database of drug targets and disease genes. The protein-protein interaction network was constructed for GO and KEGG enrichment analysis to initially explore the potential mechanism of its therapeutic effects. To construct the prognostic model, validation was performed by risk regression analysis and LASSO analysis. Finally, two prognostic genes-PIM1 and BIRC5 were determined to establish high and low risk groups. Kaplan-Meier analysis displayed a higher survival rate in the low-risk group than in the high-risk group. ROC curves indicated the stable and good effect in prediction (one-year AUC is 0.626; two-year AUC is 0.620; three-year AUC is 0.623). The interrelationship between immunity and its disease was explored by immune infiltration analysis. Finally, the potential effect of puerarin on endometrial carcinoma cells was further verified by experiments.

摘要

子宫内膜癌是近年来死亡率和发病率上升的两种癌症之一。鉴于其治疗存在诸多争议,迫切需要构建新的预后模型并寻找新的治疗方向。葛根素作为一种在中国临床治疗和实验研究中广泛应用的小分子药物,最近已被证明在多种癌细胞中具有明显的抗癌作用。在这项研究中,通过构建药物靶点和疾病基因数据库,运用生物信息学分析和实验验证来探讨葛根素治疗子宫内膜癌的潜在机制并构建预后模型。共发现 22 个与药物相关的差异基因。通过对 GO 和 KEGG 富集分析构建蛋白质-蛋白质相互作用网络,初步探讨其治疗效果的潜在机制。通过风险回归分析和 LASSO 分析进行验证,以构建预后模型。最后,确定两个预后基因 PIM1 和 BIRC5,建立高低风险组。Kaplan-Meier 分析显示低风险组的生存率高于高风险组。ROC 曲线表明其在预测中的稳定良好效果(一年 AUC 为 0.626;两年 AUC 为 0.620;三年 AUC 为 0.623)。通过免疫浸润分析探讨了免疫与其疾病之间的相互关系。最后,通过实验进一步验证了葛根素对子宫内膜癌细胞的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46ad/9175360/2b841ed051a2/12906_2022_3623_Fig1_HTML.jpg

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