利用定量蛋白质组学分析鉴定醛固酮腺瘤中新型生物标志物和通路
Discovery of novel biomarkers and pathways in aldosterone-producing adenomas through label-free quantitative proteomics analysis
陈亮 1向婉 2代喆 3余方 4孟哲1
作者信息
- 1. 武汉大学中南医院泌尿外科(武汉,430071)
- 2. 武汉大学中南医院生物样本库
- 3. 武汉大学中南医院内分泌科
- 4. 武汉大学中南医院病理科
- 折叠
摘要
目的:本研究旨在通过对接受肾上腺切除术的患者采集的醛固酮腺瘤(aldosterone-producing ade-noma,APA)组织进行无标记定量蛋白质组学分析,筛选APA组织和正常肾上腺组织之间差异表达的蛋白.方法:利用无标记定量蛋白质组学技术对APA及正常肾上腺组织进行分析,筛选APA组织和正常肾上腺组织之间差异表达的蛋白.采用免疫组化染色对APA病人组织样本染色,验证差异表达蛋白的表达.结果:共鉴定了6 282种蛋白质.使用P＜0.05和|fold change|≥2的显著性截断值,鉴定出356种差异表达蛋白(differentially expressed proteins,DEPs).此外,通过整合蛋白质组和转录组数据,鉴定出一个新的生物标志物嗜铬蛋白B(chromogranin B,CHGB),在APA中显著表达下调,并进一步通过免疫组化染色得到了进一步验证.受试者工作特征(receiver operating characteristic,ROC)曲线分析显示,CHGB在区分正常组织和APA方面具有较高的特异性(AUC=0.856),显示其在APA发展中的潜在重要性.重要的是,CHGB和CYP11B2的联合提高了诊断APA的预测效能.结论:我们的研究确定了参与APA发生的关键蛋白质和通路,并发现了一种新的蛋白质生物标志物来区分APA,可能成为预测APA的潜在生物标记物.这些发现为未来APA的分子诊断研究提供了理论依据.
Abstract
Objective:To identify differentially expressed proteins between aldosterone-producing adenoma(APA)tissue and normal adrenal tissue through label-free quantitative proteomics analysis of APA tissue collected from patients undergoing adrenal resection.Methods:The APA and normal adrenal tissue were analyzed using la-bel-free quantitative proteomics analysis to identify differentially expressed proteins.Immunohistochemical stai-ning was used to validate the expression differences of the identified proteins between APA and normal tissue in patient samples.Results:A total of 6282 proteins were identified.Using a significance cutoff of P＜0.05 and|fold change|≥ 2 356 differentially expressed proteins were identified.Furthermore,through the integration of proteomics and transcriptomics data,a novel biomarker,chromogranin B(CHGB),was identified with significant-ly downregulated expression in APAs,which was further validated through immunohistochemical staining.ROC curve analysis showed that CHGB had high specificity in distinguishing normal tissues from APAs(AUC=0.856),indicating its potential importance in APA development.Importantly,the combination of CHGB and CYP11B2 improved the predictive efficiency for diagnosing APAs.Conclusion:Our study identified key proteins and pathways involved in APA development and discovered a novel protein biomarker for distinguishing APAs,which may serve as a potential biomarker for predicting APAs.These findings provide a theoretical basis for fu-ture molecular diagnostic research in APAs.
关键词
原发性高醛固酮症/醛固酮腺瘤/蛋白质组学分析/嗜铬蛋白B/PPAR信号通路Key words
primary aldosteronism/aldosterone-producing adenoma/proteomics analysis/chromogranin B/PPAR signaling pathway引用本文复制引用
基金项目
武汉大学中南医院青年交叉学科专项(ZNQNJC2023012)
出版年
2024
NETL
NSTL
万方数据