Salivary proteomics profiling reveals potential biomarkers for chronic kidney disease: a pilot study

• Published in: Frontiers in medicine 2025-01, Vol.11
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: biomarker; chronic kidney disease; LC–MS/MS; PI-PLC; salivary proteomic; Sgsm2
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2024.1302637

IntroductionChronic 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.MethodsWe analyzed the untargeted proteomic profiles of saliva samples from 20 individuals with end-stage kidney disease (ESKD) (n = 10) and healthy individuals (n = 10) using liquid chromatography–tandem mass spectrometry (LC–MS/MS) to identify potential biomarkers for CKD. A volcano plot was generated using a p-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.ResultsIn 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.ConclusionWe 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.