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Povzetek: Introduction: early initiation is essential for successful treatment of Fabry disease, but sensitive and noninvasive biomarkers of Fabry nephropathy are lacking. Urinary extracellular vesicles (uEVs) represent a promising source of biomarkers of kidney involvement. Among them, microRNAs (miRNAs) are important posttranscriptional regulators of gene expression that contribute to the development and progression of various kidney diseases. We aimed to identify uEV-derived miRNAs involved in the development and/or progression of Fabry nephropathy. Methods: patients with genetically confirmed Fabry disease and matched control subjects were included. EVs were isolated from the second morning urine by size exclusion chromatography, from which miRNAs were extracted. miRNA urine exosome PCR panels were used to characterize the miRNA signature in a discovery cohort. Individual qPCRs were performed on a validation cohort that included chronological samples. We identified the target genes of dysregulated miRNAs and searched for potential hub genes. Enrichment analyses were performed to identify their potential function. Results: the expression of miR-21-5p and miR-222-3p was significantly higher in patients with stable renal function and those with progressive nephropathy compared with the corresponding controls. In addition, the expression of miR30a-5p, miR-10b-5p, and miR-204-5p was significantly lower in patients with progressive nephropathy, however, in the chronological samples, this was only confirmed for miR-204-5p. Some of the identified hub genes controlled by the dysregulated miRNAs have been associated with kidney impairment in other kidney diseases. Conclusion: the miRNA cargo in uEVs changes with the development and progression of Fabry nephropathy and, therefore, represents a potential biomarker that may provide a new option to prevent or attenuate the progression of nephropathy. Furthermore, dysregulated miRNAs were shown to be potentially associated with pathophysiological pathways in the kidney.
Ključne besede: urinary miRnome profiling, microRNA, Fabry disease, nephropathy, urinary extracellular vesicles, biomarker, longitudinal study
Objavljeno v DiRROS: 01.09.2026; Ogledov: 75; Prenosov: 43
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Povzetek: Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases. Their treatment options are rather limited, and no neuroprotective or disease-modifying treatments are available. Anti-diabetic drugs, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonists, have been suggested as a potential therapeutic option. Aims: Assess GLP1R and GIPR genetic variability in relation to AD- and PD-related phenotypes. Methods: AD, PD patients and healthy control subjects were included in the study. Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease were measured in AD patients, while cognitive impairment was evaluated in PD. All participants were genotyped for three SNPs: GLP1R rs10305420, GLP1R rs6923761 and GIPR rs1800437. Results: GLP1R rs10305420 genotypes were associated with increased odds for AD and PD development. GLP1R rs10305420 and GLP1R rs6923761 genotypes were significantly associated with Aβ42/40 ratio (p = 0.041 and p = 0.050), while GLP1R rs6923761 was also associated with p-tau levels (p = 0.022). Finally, GIPR rs1800437 heterozygotes as well as carriers of at least one GIPR rs1800437 C allele presented with increased odds for the development of dementia in PD (OR = 1.92; 95 % CI = 1.05-3.51; p = 0.034 and OR = 1.95; 95 % CI = 1.08-3.52; p = 0.027, respectively). Conclusion: GLP1R and GIPR genetic variability may affect the occurrence of AD and PD and is also associated with AD CSF biomarkers for Alzheimer's disease and dementia in PD. The data on GLP1R and GIPR genetic variability may support the function of incretin receptors in neurodegeneration.
Ključne besede: Alzheimer's disease, biomarker, glucagon-like peptide 1 receptor, glucose-dependent insulinotropic polypeptide, Parkinson's disease, polymorphism
Objavljeno v DiRROS: 09.06.2026; Ogledov: 274; Prenosov: 253
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Povzetek: Background: Soluble immune checkpoints (sICs) are circulating forms of membrane-bound immune molecules, the latter being targets of immune checkpoint inhibitors, widely used in cancer treatment. Altered sIC levels have been reported in several malignancies and sICs are posited as promising diagnostic, prognostic and predictive biomarkers measurable in peripheral blood. However, data on their levels in endometrial cancer (EC) patients are scarce. This study aimed to evaluate plasma concentrations of multiple sICs in EC patients and assess their potential diagnostic, prognostic, and predictive value. Methods: In this prospective case-control study, plasma levels of 16 soluble immune checkpoints were measured in 50 patients with histologically confirmed EC prior to surgical staging and in 26 age- and BMI-matched controls undergoing benign gynecologic surgery. Fluorescence-based multiplex immunoassay (MagPix, Luminex) was used to quantify analyte concentrations. FIGO 2023 stage classification and risk grouping according to ESGO 2020 guidelines was performed based on clinicopathologic data and molecular characteristics (MMR and p53 status). Statistical analyses were performed using non-parametric tests and robust logistic regression. Results: EC and control groups did not differ in demographic, clinical, or lifestyle parameters. sIC levels were measurable in majority of patients. No significant differences in sIC levels were observed between EC patients and controls. Within the EC cohort, patients with MMR-deficient tumors exhibited significantly elevated levels of sPD-1, sPD-L1, sLAG-3, sICOS, sGITR, and sCD86 compared with MMR-proficient cases. Higher plasma concentrations of sTIM-3, sCD27, sHVEM, and sCD40 were associated with the presence of lymphovascular space invasion (LVSI). Levels of sCD27 and sCD40 were significantly higher in advanced or metastatic disease (stage IIIA or higher). Conclusions: Although soluble immune checkpoint levels did not differentiate EC patients from controls, several sICs correlated with key prognostic and predictive features, including LVSI, advanced stage, and MMR deficiency. These findings suggest that circulating immune checkpoint proteins may serve as non-invasive biomarkers for risk assessment and immunotherapy response prediction in endometrial cancer. Further validation in larger, independent cohorts is warranted.
Ključne besede: diagnosticbiomarker, endometrial cancer, immune checkpoint inhibitor, lymphovascular spaceinvasion, mismatch repair deficiency, predictive biomarker, prognostic biomarker, soluble immune checkpoint
Objavljeno v DiRROS: 18.05.2026; Ogledov: 289; Prenosov: 263
Celotno besedilo (3,08 MB)
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Povzetek: Background/Objectives: In recent years, interest in studying changes in cancer metabolites has resulted in significant advances in the metabolomics field. Glioblastoma remains the most aggressive and lethal brain malignancy, which presents with notable metabolic reprogramming. Methods: We performed literature research from the PubMed database and considered research articles focused on the key metabolic pathways altered in glioblastoma (e.g., glycolysis, lipid metabolism, TCA cycle), the role of oncometabolites and metabolic plasticity, and the differential expression of metabolites in glioblastoma. Currently used metabolomics approaches can be either targeted, focusing on specific metabolites and pathways, or untargeted, which involves data-driven exploration of the metabolome and also results in the identification of new metabolites. Data processing and analysis is of great importance and can be improved with the integration of machine learning approaches for metabolite identification. Results: Changes in α/β-glucose, lactate, choline, and 2-hydroxyglutarate were detected in glioblastoma compared with non-tumor tissues. Different metabolites such as fumarate, tyrosine, and leucine, as well as citric acid, isocitric acid, shikimate, and GABA were detected in blood and CSF, respectively. Conclusions: Although promising new technological and bioinformatic approaches help us understand glioblastoma better, challenges associated with biomarker availability, tumor heterogeneity, interpatient variability, standardization, and reproducibility still remain. Metabolomics research, either alone or combined with genomics or proteomics (i.e., multiomics) in glioblastoma, can lead to biomarker identification, tracking of metabolic therapy response, discovery of novel metabolites and pathways, and identification of potential therapeutic targets.
Ključne besede: Omics, metabolome, multiomic integration, tumor metabolic reprogramming, biomarker, diagnosis, therapy, precision oncology
Objavljeno v DiRROS: 22.04.2026; Ogledov: 313; Prenosov: 294
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Povzetek: Growth arrest-specific protein 6 (GAS6) has an important role in regulating the immune system. Recent studies have revealed its association with the pathophysiology of endometriosis and identified GAS6 as one of the hub genes and a biomarker candidate. Endometriosis is a common chronic inflammatory gynaecological disease of women of childbearing age. Due to surgical diagnosis, non-invasive biomarkers are urgently needed. We investigated GAS6 as a candidate biomarker for the diagnosis of endometriosis. Our case-control study included 284 patients and showed that plasma levels of GAS6 are significantly higher in patients with endometriosis compared to control patients. We calculated logistic regression models using GAS6, CA-125, and GAS6 together with CA-125, and added a series of clinical and lifestyle data collected before surgical diagnosis. A CA-125 model and a model including GAS6 and CA-125 showed the highest AUC values of 0.745 ± 0.04, while the model including CA-125, data on sport/recreation before surgery, and dysmenorrhea score reached an AUC of 0.767 ± 0.04. Our results indicate that GAS6 is increased in patients with endometriosis, but it cannot serve as a biomarker candidate.
Ključne besede: CA-125, GAS6, biomarker discovery, endometriosis, logistic regression
Objavljeno v DiRROS: 14.04.2026; Ogledov: 336; Prenosov: 247
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