Peptides as “better biomarkers”? Value, challenges, and potential solutions to facilitate implementation

Abstract

Peptides carry important functions in normal physiological and pathophysiological processes and can serve as clinically useful biomarkers. Given the ability to diffuse passively across endothelial barriers, endogenous peptides can be examined in several body fluids, including among others urine, blood, and cerebrospinal fluid. This review article provides an update on the recently published literature that reports on investigating native peptides in body fluids using mass spectrometry‐based platforms, specifically those studies that focus on the application of peptides as biomarkers to improve clinical management. We emphasize on the critical evaluation of their clinical value, how close they are to implementation, and the associated challenges and potential solutions to facilitate clinical implementation. During the last 5 years, numerous studies have been published, demonstrating the increased interest in mass spectrometry for the assessment of endogenous peptides as potential biomarkers. Importantly, the presence of few successful examples of implementation in patients' management and/or in the context of clinical trials indicates that the peptide biomarker field is evolving. Nevertheless, most studies still report evidence based on small sample size, while validation phases are frequently missing. Therefore, a gap between discovery and implementation still exists.

Application of Urinary Peptide-Biomarkers in Trauma Patients as a Predictive Tool for Prognostic Assessment, Treatment Interventions, and Intervention Timing: Prospective Nonrandomized Pilot Study

“…For the definition of urinary peptides significantly associated with trauma, the urinary peptide data of 14 polytraumatized patients and 14 age-and sex-matched healthy controls from the Human Urinary Peptide Database were used (32). This comparison revealed that 281 peptides were significantly affected (p<0.05, Wilcoxon test followed by adjustment for multiple comparisons by Benjamini and Hochberg).…”

Comparison of Peptidomes Extracted from Healthy Tissue, Tumour Tissue of the Parotid Glands and Saliva Samples

“…The peptidome -consisting of thousands of peptides: remnants of protein degradation; specific precursor-derived peptides such as hormones, cytokines, or growth factors; and translation products of small open reading frames (smORFs) [16] responds dynamically to changes in the body, providing a rich source of potential biomarkers. This results in the rapid expansion of peptidomics research observed in recent years [17,18], demonstrating characteristic peptidomic patterns of many diseases, including various types of cancer [19][20][21]. Furthermore, it has been shown that peptidomic analyses can detect statistically significant differences observed in bottom-up proteomics [22].…”

Impact of Renal Denervation on Urinary Peptide-Based Biomarkers in Hypertension

“…In that context, naturally occurring peptides might be highly relevant, having the capacity to diffuse passively across endothelial barriers and, as such, sharing important functions in different physiological and pathophysiological processes. 6 Urinary peptides, which are stable as degradation is essentially completed by the time of urination, 6 have been associated with CKD and heart disease, including coronary artery disease (CAD) and HF, and provide prognostic information. 6,7 In CKD, for example, in a multicenter, prospective, observational study with embedded randomized controlled trial (Proteomic Prediction and Renin Angiotensin Aldosterone System Inhibition Prevention Of Early Diabetic nephropathy In Type 2 Diabetic Patients With Normoalbuminuria [PRORITY] trial), urinary peptides were used to identify high-risk patients who may benefit from early interventions.…”

“…6,7 In CKD, for example, in a multicenter, prospective, observational study with embedded randomized controlled trial (Proteomic Prediction and Renin Angiotensin Aldosterone System Inhibition Prevention Of Early Diabetic nephropathy In Type 2 Diabetic Patients With Normoalbuminuria [PRORITY] trial), urinary peptides were used to identify high-risk patients who may benefit from early interventions. 6…”

“…This study investigated the impact of RDN on validated peptide-based classifiers associated with CKD (CKD273) 6,8 and heart diseases (CAD238 9 and HF1 10 ). Moreover, we aimed to identify urinary peptides affected by RDN.…”