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辣椒素对子宫内膜癌作用机制的研究及实验验证

Mechanism investigation and experiment validation of capsaicin on uterine corpus endometrial carcinoma.

作者信息

Lin Zhiheng, Sui Xiaohui, Jiao Wenjian, Chen Chong, Zhang Xiaodan, Zhao Junde

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, China.

Obstetrics Department of Affiliated Hospital of Weifang Medical College, Weifang, China.

出版信息

Front Pharmacol. 2022 Sep 21;13:953874. doi: 10.3389/fphar.2022.953874. eCollection 2022.

Abstract

Using bioinformatics analysis and experimental operations, we intend to analyze the potential mechanism of action of capsaicin target gene GATA1 in the treatment of uterine corpus endometrial carcinoma (UCEC) and develop a prognostic model for the disease to validate this model. By obtaining capsaicin and UCEC-related DR-DEGs, the prognosis-related gene GATA1 was screened. The survival analysis was conducted via establishing high and low expression groups of GATA1. Whether the GATA1 could be an independent prognostic factor for UCEC, it was also validated. The therapeutic mechanism of capsaicin-related genes in UCEC was further investigated using enrichment analysis and immune methods as well as in combination with single-cell sequencing data. Finally, it was validated by cell experiments. GATA1, a high-risk gene associated with prognosis, was obtained by screening. Kaplan-Meier analysis showed that the survival of the high expression group was lower than that of low expression group. ROC curves showed that the prediction effect of the model was good and stable (1-year area under curve (AUC): 0.601; 2-years AUC: 0.575; 3-years AUC: 0.610). Independent prognosis analysis showed that the GATA1 can serve as an independent prognostic factor for UCEC. Enrichment analysis showed that "neuroactive Ligand - receptor interaction and TYPE I DIABETES MELLITUS" had a significant enrichment effect. Single-cell sequencing showed that the GATA1 was significantly expressed in mast cells. Cell experiments showed that the capsaicin significantly reduced the UCEC cell activity and migration ability, as well as inhibited the expression of GATA1. This study suggests that the capsaicin has potential value and application prospect in the treatment of UCEC. It provides new genetic markers for the prognosis of UCEC patients.

摘要

通过生物信息学分析和实验操作,我们旨在分析辣椒素靶基因GATA1在子宫内膜癌(UCEC)治疗中的潜在作用机制,并建立该疾病的预后模型以验证此模型。通过获取辣椒素和UCEC相关的差异表达基因(DR-DEGs),筛选出与预后相关的基因GATA1。通过建立GATA1的高表达组和低表达组进行生存分析。还验证了GATA1是否可以作为UCEC的独立预后因素。使用富集分析和免疫方法,并结合单细胞测序数据,进一步研究了辣椒素相关基因在UCEC中的治疗机制。最后,通过细胞实验进行验证。通过筛选获得了与预后相关的高风险基因GATA1。Kaplan-Meier分析表明,高表达组的生存率低于低表达组。ROC曲线显示该模型的预测效果良好且稳定(1年曲线下面积(AUC):0.601;2年AUC:0.575;3年AUC:0.610)。独立预后分析表明,GATA1可作为UCEC的独立预后因素。富集分析表明,“神经活性配体-受体相互作用和I型糖尿病”具有显著的富集效应。单细胞测序显示,GATA1在肥大细胞中显著表达。细胞实验表明,辣椒素显著降低了UCEC细胞的活性和迁移能力,并抑制了GATA1的表达。本研究表明,辣椒素在UCEC治疗中具有潜在价值和应用前景。它为UCEC患者的预后提供了新的遗传标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85b8/9532580/1b19c433f3c1/fphar-13-953874-g001.jpg

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