Picolo Bianca Uliana, Silva Nathália Rabello, Martins Mário Machado, Almeida-Souza Hebréia Oliveira, de Sousa Letícia Cristina Machado, Polveiro Richard Costa, Goulart Filho Luiz Ricardo, Sabino-Silva Robinson, Alonso-Goulart Vivian, Saraiva da Silva Luciana
Laboratory of Nanobiotechnology Prof. Dr. Luiz Ricardo Goulart Filho, Institute of Biotechnology, Federal University of Uberlândia, Uberlândia, Brazil.
Faculty of Medicine, Federal University of Uberlândia, Uberlândia, Brazil.
Front Med (Lausanne). 2025 Jan 17;11:1302637. doi: 10.3389/fmed.2024.1302637. eCollection 2024.
Chronic kidney disease (CKD) is a global public health problem, and the absence of reliable and accurate diagnostic and monitoring tools contributes to delayed treatment, impacting patients' quality of life and increasing treatment costs in public health. Proteomics using saliva is a key strategy for identifying potential disease biomarkers.
We analyzed the untargeted proteomic profiles of saliva samples from 20 individuals with end-stage kidney disease (ESKD) ( = 10) and healthy individuals ( = 10) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify potential biomarkers for CKD. A volcano plot was generated using a -value of ≤0.05 and a fold change (FC) ≥ 2.0. Multivariate analysis was performed to generate the orthogonal partial least squares discriminant analysis (OPLS-DA) model and the variable importance in projection (VIP) scores. The accuracy of candidate biomarker proteins was evaluated using receiver operating characteristic (ROC) curves.
In total, 431 proteins were identified in the salivary proteomic profile, and 3 proteins were significantly different between the groups: apoptosis inhibitor 5 (API5), phosphoinositide phospholipase C (PI-PLC), and small G protein signaling modulator 2 (Sgsm2). These proteins showed good accuracy based on the ROC curve and a VIP score of >2.0. During pathway enrichment, PI-PLC participates in the synthesis of IP3 and IP4 in the cytosol. Gene ontology (GO) analysis revealed data on molecular functions, biological processes, cellular components, and protein classes.
We can conclude that the salivary API5, PI-PLC, and Sgsm2 can be potential biomarker candidates for CKD detection. These proteins may participate in pathways related to renal fibrosis and other associated diseases, such as mineral and bone disorders.
慢性肾脏病(CKD)是一个全球性的公共卫生问题,缺乏可靠且准确的诊断和监测工具会导致治疗延误,影响患者生活质量,并增加公共卫生领域的治疗成本。利用唾液进行蛋白质组学分析是识别潜在疾病生物标志物的关键策略。
我们使用液相色谱-串联质谱(LC-MS/MS)分析了20名终末期肾病(ESKD)患者(n = 10)和健康个体(n = 10)唾液样本的非靶向蛋白质组图谱,以识别CKD的潜在生物标志物。使用p值≤0.05和倍数变化(FC)≥2.0生成火山图。进行多变量分析以生成正交偏最小二乘判别分析(OPLS-DA)模型和投影变量重要性(VIP)得分。使用受试者工作特征(ROC)曲线评估候选生物标志物蛋白的准确性。
在唾液蛋白质组图谱中总共鉴定出431种蛋白质,两组之间有3种蛋白质存在显著差异:凋亡抑制因子5(API5)、磷酸肌醇磷脂酶C(PI-PLC)和小G蛋白信号调节因子2(Sgsm2)。基于ROC曲线和VIP得分>2.0,这些蛋白质显示出良好的准确性。在通路富集过程中,PI-PLC参与细胞质中IP3和IP4的合成。基因本体(GO)分析揭示了有关分子功能、生物学过程、细胞成分和蛋白质类别的数据。
我们可以得出结论,唾液中的API5、PI-PLC和Sgsm2可能是用于CKD检测的潜在生物标志物候选物。这些蛋白质可能参与与肾纤维化和其他相关疾病(如矿物质和骨代谢紊乱)相关的通路。