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Association between altered levels of urinary extracellular vesicles pre- and post-surgery and prognosis in patients with breast cancer: A pilot study

ABSTRACT: Urinary extracellular vesicles (uEVs) have shown potential as non-invasive biomarkers for various cancers. However, research on the relationship between uEVs levels and cargo changes after breast cancer surgery remains limited. Therefore, we investigated changes in uEVs levels and proteomes in patients with breast cancer (BC) pre- and post-surgery.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Raphatphorn Navakanitworakul

PROVIDER: PXD061107 | JPOST Repository | Tue Feb 24 00:00:00 GMT 2026

REPOSITORIES: jPOST

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			Action	DRS
	uEV_N60_RE8_01_28057.mzXML	Mzxml
	uEV_N60_RE8_01_28058.mzXML	Mzxml
	uEV_N60_RE8_01_28059.mzXML	Mzxml
	uEV_N61_GB1_01_28060.mzXML	Mzxml
	uEV_N61_GB1_01_28061.mzXML	Mzxml

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Project description:Objectives: Secretion of extracellular vesicles (EV) and associated micro-RNAs (miR) is altered during cellular stress and may serve as biomarkers of organ injury. We hypothesized that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. Design: Predictive accuracy biomarker study performed in the cohort of the REVAKI-2 trial Setting: Single center ICU between September 2015 and September 2018 Interventions: Intravenous sildenafil citrate 12.5 mg kg-1 over 150 min or dextrose 5% at the commencement of surgery. Measurements and main results: Urine samples were collected before and 24 hours after the procedure from 93 cardiac surgery patients. Urine EV concentrations and size distribution were assessed using NanoSight. EV derivation and levels were measured using flow cytometry. Samples from 10 selected patients were sequenced to detect differentially expressed miR. Verification was performed with advanced TaqMan assays in samples from all patients. Urine EV concentrations significantly increased in patients with AKI after surgery, with the percentage of EV positive for aquaporin-2 and β1-integrin also increasing. Pre surgery podocalyxin-positive EV were significantly lower, and β1-integrin EV werehigher in patients with AKI. The levels of the former correlated with the severity of theinjury. miR-125a-5p was expressed at higher levels in urine from patients with AKI stage 2/3. Levels of miR-10a-5p decreased after surgery in AKI patients; its levels correlated with the severity of the injury. Preoperative levels of podocalyxin EVs and miR-125a-5p had moderate AKI predictive value and, in a logistic model together with ICU lactate levels, offered good (AUC = 80.9%) AKI prediction. Conclusions: Lower levels of podocalyxin-positive EV at baseline predict the severity of post-surgery AKI. Urine EV concentrations and miR expression offer excellent predictive accuracy when combined with commonly measured biomarkers.

Project description:Weight loss induced by bariatric surgery (BS) is recognized for having a profound impact on several biological systems. This study aimed to characterize the urinary proteomic profile in individuals with obesity before and after BS, to identify urinary proteins that reflect the kidney and systemic adaptations to weight loss. Urine samples from individuals with obesity (n=16) undergoing BS were collected before and two-years after surgery. Untargeted high-resolution liquid chromatography–mass spectrometry (LC-MS) with label-free quantification (LFQ) was used to assess changes in the urinary proteome. A total of 2347 proteins were identified in the urine. Among these, 1016 depicted a significantly different expression post-surgery (p<0.05). In particular, 54 proteins were identified with at least 50% change (≥1.5-fold), either upregulated (n=42) or downregulated (n=12). Functional classification of these top altered proteins revealed an association with immune function (n=17; e.g., protein S100-A9, alpha-1-acid glycoproteins 1 and 2); cytoskeleton/cell adhesion (n=11; e.g., supervillin, ezrin, periplakin) and kidney adaptation (n=11; e.g., elongation factor 1-alpha 1, cystatin-B, megalin, cubilin). A decrease in inflammation protein markers (alpha-1-acid glycoproteins), alongside an increase in proteins associated with immune modulation and oxidative stress protection (dipeptidase 1 and heat shock cognate 71 kDa protein) were also observed post-surgery. Additionally, changes in cytoskeletal and extracellular matrix proteins were identified, as well as proteins present in specific kidney cell components and tubular processes. The most significant modifications found in the urinary proteome following BS were proteins primarily associated with decreased inflammation and oxidative stress, as well as cytoskeletal and extracellular matrix proteins. Overall, our results reveal potential novel pathways contributing to systemic modifications and nephroprotective effects of BS induced weight loss.

Dataset Information

Association between altered levels of urinary extracellular vesicles pre- and post-surgery and prognosis in patients with breast cancer: A pilot study

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