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Abstract: Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune necrotizing small vessel vasculitis, frequently resulting in severe renal manifestations such as rapidly progressive glomerulonephritis (AAV-GN). Monitoring disease activity and determining ongoing renal involvement remain significant clinical challenges due to the limitations associated with traditional biomarkers. This study focused on the potential of circulating microRNA (miRNA) as supplementary noninvasive biomarkers for disease activity in AAV-GN. Methods: This prospective follow-up study involved serum samples from 60 patients with biopsy-proven AAV-GN, collected at renal biopsy and at 3-, 6-, 12-, and 24-month intervals post-biopsy. Nine miRNAs (miR-21-3p, miR-30b/d/e-5p, miR-142-5p, miR-150-5p, miR-181a-5p, miR-181b-5p, and let-7a-5p) were selected based on the differential expressions in renal tissue and corresponding serum samples identified in the previous research phases. Expression analysis was performed using quantitative real-time polymerase chain reaction and correlated with disease activity based on the Birmingham Vasculitis Activity Score and other clinical parameters. Results: A significant correlation was identified between disease activity and the expression levels of the miR-30 family members and let-7a. Specifically, these miRNAs demonstrated consistent correlation patterns across follow-up samples independent of the time elapsed post-biopsy, with down-regulation correlating with the presence of active disease. Notably, the miRNA expression profile in partial remission appeared analogous to that of complete remission, suggesting that many patients categorized as having partial remission may, in fact, be considered in true clinical remission. Conclusion: This study supports serum miRNA profiling as an adjunct noninvasive biomarker for assessing disease activity in AAV-GN. Such an approach could provide complementary information alongside traditional biomarkers and refine the future management of AAV-GN. However, it is important to acknowledge that our actual study cohort was small due to challenging technical aspects of miRNA expression analysis in the serum. Therefore, further research with larger cohorts is required to validate these results and assess their clinical applicability.
Keywords: ANCA, vasculitis, glomerulonephritis, microRNA, biomarker, BVAS, epigenetics, follow-up
Published in DiRROS: 26.11.2025; Views: 625; Downloads: 407
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Abstract: Background. Glioblastoma (GBM) is the most common and the most malignant glioma subtype. Among numerous genetic alterations, miRNAs contribute to pathogenesis of GBM and it is suggested that also to GBM recurrence and resistance to therapy. Based on publications, we have selected 11 miRNAs and analyzed their expression in GBM. We hypothesized that selected miRNAs are differentially expressed and involved in primary as well as in recurrent GBM, that show significant expressional differences when different treatment options are in question, and that are related to certain patients and tumor characteristics. Patients and methods. Paraffin embedded tissues, obtained from primary and corresponding recurrent tumor from 83 patients with primary GBM were used. Eleven miRNAs ( miR-7, miR-9, miR-15b, miR-21, miR-26b, miR-124a, miR-199a, let-7a, let-7b, let-7d, and let-7f ) were selected for qPCR expression analysis. For patients who received temozolamide (TMZ) as chemotherapeutic drug, O6-methylguanine-DNA methyltransferase (MGMT) methylation status was defined using the methyl-specific PCR. Results. There was a significant change in expression of miR-7, miR-9, miR-21, miR-26b, mirR-124a, miR-199a and let- 7f in recurrent tumor compared to the primary. In recurrent tumor, miR-15b, let-7d and let-7f significantly changed comparing both treatment options. We also observed difference in progression free survival between patients that received radiotherapy and patients that received radiotherapy and chemotherapy, and longer survival for patients who received chemotherapy after second surgery compared to not treated patients. miR-26b showed correlation to progression free survival and let-7f to overall survival. We did not find any expression difference between the tumors with and without methylated MGMT. Conclusions. Our data suggest that analyzed miRNAs may not only contribute to pathogenesis of primary GBM, but also to tumor progression and its recurrence. Moreover, expression of certain miRNAs appears to be therapy- dependent and as such they might serve as additional biomarker for recurrence prediction and potentially predict a therapy-resistance.
Keywords: glioblastoma, radiotherapy, chemotherapy
Published in DiRROS: 02.07.2024; Views: 1422; Downloads: 905
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Abstract: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months. Control group were 40 patients with shorter survival and matched to the long-term survivor group according to the clinical prognostic factors. All patients underwent multimodality treatment with surgery, postoperative conformal radiotherapy and temozolomide during and after radiotherapy. Biopsy samples were tested for the methylation of MGMT promoter (with methylation specific polymerase chain reaction), IDH1 (with immunohistochemistry), IDH2, CDKN2A and CDKN2B (with multiplex ligation-dependent probe amplification), and 1p and 19q mutations (with fluorescent in situ hybridization). Methylation of MGMT promoter was found in 95% and in 36% in the long-term survivor and control groups, respectively (p < 0.001). IDH1 R132H mutated patients had a non-significant lower risk of dying from glioblastoma (p= 0.437), in comparison to patients without this mutation. Other mutations were rare, with no significant difference between the two groups. Molecular and genetic testing offers additional prognostic and predictive information for patients with glioblastoma. The most important finding of our analysis is that in the absence of MGMT promoter methylation, longterm survival is very rare. For patients without this mutation, alternative treatments should be explored.
Keywords: glioblastoma, long-term survival, methyl guanine methyl transferase, MGMT, prognostic factor
Published in DiRROS: 30.04.2024; Views: 1435; Downloads: 1084
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