Dataset Information

Longitudinal landscape of urinary EV proteome reveals stable protein expression patterns within and between individuals

ABSTRACT: Urinary extracellular vesicles (EVs) are an attractive source for the detection of disease biomarkers. Mass spectrometry (MS) based proteomics is increasingly used for urinary EV proteome profiling and protein biomarker discovery. However, little is known about the consistency and stability of urinary EV proteins within individuals over time and between different individuals. In this study we profiled the urinary EV proteome of 8 healthy individuals over 6 months at 9 timepoints (total 72 samples) using DIA-MS. We identified a total of 1802 proteins with high correlation amongst all samples. While a minor fraction (10%) of the total urinary EV proteome was shown to play a role in determining personal expression patterns, most of the urinary EV proteins was found to be stable with >90% of the proteins detected in more than 1 person at all timepoints. The variability of urinary EV proteome between different individuals was shown to be significantly higher than personal variation as a result of a small subset (<20%) of proteins. The core interaction network of proteins identified in all individuals revealed EV proteins involved in signaling and localization and sub-clusters enriched for glycolytic activity, protein synthesis, and immune function. Gender-specific expression patterns were detected in the urinary EV proteome, mostly related to hormonal and reproduction pathways. In summary, our findings indicate that the urinary EV proteome is stable in longitudinal samples of healthy subjects, underscoring its potential as a reliable source for protein biomarkers.

INSTRUMENT(S): Q Exactive HF, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

SUBMITTER: Sander Piersma

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD022983 | Pride | 2021-09-09

REPOSITORIES: Pride

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Publications

Longitudinal stability of urinary extracellular vesicle protein patterns within and between individuals.

Erozenci Leyla A LA Piersma Sander R SR Pham Thang V TV Bijnsdorp Irene V IV Jimenez Connie R CR

Scientific reports 20210802 1

The protein content of urinary extracellular vesicles (EVs) is considered to be an attractive non-invasive biomarker source. However, little is known about the consistency and variability of urinary EV proteins within and between individuals over a longer time-period. Here, we evaluated the stability of the urinary EV proteomes of 8 healthy individuals at 9 timepoints over 6 months using data-independent-acquisition mass spectrometry. The 1802 identified proteins had a high correlation amongst a ...[more]

PMID: 34341426

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Project description:Cystinuria is the most frequent monogenic cause of renal calculi. We previously described a urinary inflammatory signature in 8 cystinuric patients through quantitative proteomic analysis. Our data suggested an association of abnormal renal function and an inflammatory protein profile. The objectives of the present study were to investigate: i) the urinary proteomic profile in cystinuric patients without chronic kidney disease (CKD), and in a control group of healthy volunteers; ii) the potential effect of urine alkalinization on the urinary proteomic profile in cystinuric patients as this is the cornerstone of the preventive medical treatment. Urinary inflammatory profile was evaluated at baseline in the control group and in cystinuric patients not yet treated or for whom the alkalizing treatment or the cysteine- binding thiols have been discontinuated for at least 3 months and with an eGFR (using the CKD-EPI formula) greater than 60 ml/min/1.73m2 (so without CKD G3-G5). In cystinuric patients, change from baseline urinary inflammatory profile was evaluated after 3 months of alkalizing treatment. Urine proteome was analyzed by Nano- liquid chromatography coupled to high resolution mass spectrometry. Twenty-one cystinuric patients (12 men, median age [IQR] 30.0 years [25.0 – 44.0]), and 7 healthy volunteers (2 men, median age 43.1 years [31.0 – 53.9]) were included. Median eGFR in these two groups was 95 ml/min/1.73m2 [87.5 – 111.5] and 116 ml/min/1.73m2 [91.0 – 120.0] respectively (p=0.38). Healthy volunteers had no inflammatory signature. The inflammatory signature was present in the cystinuric patients at different degrees. A hierarchical clustering of the cystinuric patients according to the intensity of the profile of core inflammation signature (11 proteins) was performed. The signature could clearly separate 5 cystinuric patients with a high inflammation from other cystinuric patients and healthy volunteers. The alkalizing treatment was associated with a decrease in the intensity of the urinary inflammatory profile in all 5 cystinuric patients compared to the initial high level of urinary inflammation. A panel of 11 proteins was found as elevated in some cystinuric patients without CKD G3- G5 and could work as an early inflammatory signature. The alkalizing treatment was associated with a reduction of this urinary inflammation signature, suggesting that this panel of proteins could also be a new tool to monitor the treatment of cystinuric patient.

Dataset Information

Longitudinal landscape of urinary EV proteome reveals stable protein expression patterns within and between individuals

Publications

Longitudinal stability of urinary extracellular vesicle protein patterns within and between individuals.

Similar Datasets

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