Screening candidate diagnostic biomarkers for diabetic kidney disease

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY Journal of Clinical Laboratory Analysis Pub Date : 2024-02-01 DOI:10.1002/jcla.25000

Xinying Huang, Hui Zhang, Jihong Liu, Xuejiao Yang, Zijie Liu

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Abstract

Background

There are big differences in treatments and prognosis between diabetic kidney disease (DKD) and non-diabetic renal disease (NDRD). However, DKD patients couldn't be diagnosed early due to lack of special biomarkers. Urine is an ideal non-invasive sample for screening DKD biomarkers. This study aims to explore DKD special biomarkers by urinary proteomics.

Materials and Methods

According to the result of renal biopsy, 142 type 2 diabetes mellitus (T2DM) patients were divided into 2 groups: DKD (n = 83) and NDRD (n = 59). Ten patients were selected from each group to define urinary protein profiles by label-free quantitative proteomics. The candidate proteins were further verifyied by parallel reaction monitoring (PRM) methods (n = 40). Proteins which perform the same trend both in PRM and proteomics were verified by enzyme-linked immunosorbent assays (ELISA) with expanding the sample size (n = 82). The area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of diagnostic biomarkers.

Results

We identified 417 peptides in urinary proteins showing significant difference between DKD and NDRD. PRM verification identified C7, SERPINA4, IGHG1, SEMG2, PGLS, GGT1, CDH2, CDH1 was consistent with the proteomic results and p < 0.05. Three potential biomarkers for DKD, C7, SERPINA4, and gGT1, were verified by ELISA. The combinatied SERPINA4/Ucr and gGT1/Ucr (AUC = 0.758, p = 0.001) displayed higher diagnostic efficiency than C7/Ucr (AUC = 0.632, p = 0.048), SERPINA4/Ucr (AUC = 0.661, p = 0.032), and gGT1/Ucr (AUC = 0.661, p = 0.029) respectively.

Conclusions

The combined index SERPINA4/Ucr and gGT1/Ucr can be considered as candidate biomarkers for diabetic nephropathy after adjusting by urine creatinine.

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筛选糖尿病肾病的候选诊断生物标志物。

背景：糖尿病肾病（DKD）和非糖尿病肾病（NDRD）在治疗和预后方面存在很大差异。然而，由于缺乏特殊的生物标志物，糖尿病肾病患者无法得到早期诊断。尿液是筛查 DKD 生物标志物的理想无创样本。本研究旨在通过尿液蛋白质组学探索DKD的特殊生物标志物：根据肾活检结果，将 142 名 2 型糖尿病（T2DM）患者分为 2 组：DKD（83 人）和 NDRD（59 人）。每组选取 10 名患者，通过无标记定量蛋白质组学确定尿液蛋白质谱。候选蛋白质通过平行反应监测（PRM）方法进一步验证（n = 40）。通过酶联免疫吸附试验（ELISA）对在平行反应监测（PRM）和蛋白质组学中表现出相同趋势的蛋白质进行验证，并扩大样本量（n = 82）。接受者操作特征曲线下面积（AUC）用于评估诊断生物标志物的准确性：结果：我们在尿蛋白中发现了 417 种肽，它们在 DKD 和 NDRD 之间存在显著差异。PRM验证确定的C7、SERPINA4、IGHG1、SEMG2、PGLS、GGT1、CDH2、CDH1与蛋白质组结果和P结论一致：经尿肌酐调整后，SERPINA4/Ucr 和 gGT1/Ucr 的组合指标可被视为糖尿病肾病的候选生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Laboratory Analysis 医学-医学实验技术

CiteScore

5.60

自引率

7.40%

发文量

584

审稿时长

6-12 weeks

期刊介绍： Journal of Clinical Laboratory Analysis publishes original articles on newly developing modes of technology and laboratory assays, with emphasis on their application in current and future clinical laboratory testing. This includes reports from the following fields: immunochemistry and toxicology, hematology and hematopathology, immunopathology, molecular diagnostics, microbiology, genetic testing, immunohematology, and clinical chemistry.