Expert Review of Proteomics ( IF 3.4 ) Pub Date : 2021-03-04 , DOI: 10.1080/14789450.2021.1890588 Nimisha Gupta 1 , Tahreem Sahar 1 , Sapna Khowal 1 , Ishfaq Ahmad Ganaie 1 , Mohd Mughees 1 , Dinesh Khullar 2 , S K Jain 3 , Saima Wajid 1
ABSTRACT
Objectives
Renal amyloidosis (RA) is a rare disease, typically manifested with proteinuria, nephrotic syndrome, and ultimately leads to renal failure. The present study aims to profile the proteomes of renal amyloidosis patient’s serum and healthy controls, along with relative quantification to find out robust markers for RA.
Methods
In this study, 12 RA patients and their corresponding age and gender-matched healthy controls were recruited from the Nephrology department of Max Super Specialty Hospital, New Delhi. We employed gel-based proteomic approach coupled with MALDI-TOF MS to compare protein expression patterns in RA patients and controls. Furthermore, validation of differential proteins (selected) was done using bio-layer interferometry.
Results
Eleven proteins showed remarkably altered expression levels. Moreover, expression modulation of three proteins (LLPH, SLC25A51, and CHMP2B) was validated which corroborated with two-dimensional gel electrophoresis (2-DE) results showing significant upregulation (p < 0.05) in RA patients followed by ROC analysis which demonstrated the diagnostic potential of these proteins. A protein-protein master network was generated implicating the above identified proteins along with their interactors, fishing out the routes leading to amyloidosis.
Conclusion
This study indicates that the identified serum proteomic signatures could improve early diagnosis and lead to possible therapeutic targets in RA.
中文翻译:
继发性肾淀粉样变性中 CHMP2B、LLPH 和 SLC25A51 蛋白的差异水平
摘要
目标
肾淀粉样变(RA)是一种罕见的疾病,通常表现为蛋白尿、肾病综合征,最终导致肾功能衰竭。本研究旨在分析肾淀粉样变性患者血清和健康对照的蛋白质组,并进行相对量化以找出 RA 的可靠标志物。
方法
在这项研究中,从新德里 Max Super Specialty Hospital 的肾脏科招募了 12 名 RA 患者及其相应年龄和性别匹配的健康对照。我们采用基于凝胶的蛋白质组学方法与 MALDI-TOF MS 相结合来比较 RA 患者和对照组的蛋白质表达模式。此外,使用生物层干涉仪对差异蛋白质(选定)进行验证。
结果
十一种蛋白质表现出显着改变的表达水平。此外,验证了三种蛋白质(LLPH、SLC25A51 和 CHMP2B)的表达调节,这证实了二维凝胶电泳 (2-DE) 结果显示在 RA 患者中显着上调 (p < 0.05),随后 ROC 分析证明了诊断这些蛋白质的潜力。生成了一个蛋白质-蛋白质主网络,涉及上述确定的蛋白质及其相互作用物,找出导致淀粉样变性的途径。
结论
该研究表明,确定的血清蛋白质组学特征可以改善早期诊断并导致 RA 可能的治疗靶点。