Karcinom prostaty je jedním z nejčastějších onkologických onemocnění mužů ve světě. Diagnostika a stratifikace pacientů jsou klíčové pro zajištění včasné a adekvátní terapie. Současné standardy se opírají převážně o PSA, jehož nádorová specificita je limitována. Tento přehled se zaměřuje na neinvazivní potenciální onkomarkery získané z moči včetně oxidačního stresu, metabolomiky a analýzy nukleových kyselin. V rámci některých studií se ukazuje, že zvýšené hladiny markerů jako F2-isoprostanáza, sarcosin a PCA3 mohou indikovat přítomnost a agresivitu karcinomu prostaty. Nové kombinované testy Prostarix, Mi-Prostate Score, SelectMDX nebo ExoDX nabízejí potenciál pro zlepšení stratifikace pacientů a snížení počtu negativních biopsií. Klinické využití těchto nových markerů je zatím omezené. Vzhledem k heterogenitě tohoto onemocnění je nezbytné pokračovat ve výzkumu, který usnadní personalizovaný přístup v léčbě.
Prostate cancer is one of the most common oncological diseases among men worldwide. Accurate diagnosis and patient stratification are crucial for ensuring timely and appropriate therapy. Current standards primarily rely on PSA, whose tumor specificity is limited. This review focuses on non-invasive potential oncological markers derived from urine, including oxidative stress, metabolomics and nucleic acid analysis. Some studies indicate that elevated levels of markers such as F2-isoprostane, sarcosine or PCA3 may signify the presence and aggressiveness of prostate cancer. New combined tests Prostarix, Mi-Prostate Score, SelectMDX and ExoDX offer potential for improved diagnosis and patient stratification, as well as a reduction in negative biopsies. However, the clinical application of these new markers remains limited. Considering the heterogeneity of this disease, ongoing research is essential to support a personalized approach to treatment.
- MeSH
- Amino Acids urine MeSH
- Biopsy methods MeSH
- Early Detection of Cancer methods MeSH
- Molecular Diagnostic Techniques MeSH
- Exosomes physiology MeSH
- Humans MeSH
- Metabolomics methods MeSH
- MicroRNAs urine MeSH
- Biomarkers, Tumor * urine MeSH
- Prostatic Neoplasms * diagnosis MeSH
- Oxidative Stress physiology MeSH
- Prostate-Specific Antigen blood MeSH
- Check Tag
- Humans MeSH
MicroRNAs (miRNAs) are endogenous noncoding RNAs, which regulate gene expression on the post-transcriptional level. Since miRNAs are involved in the regulation of apoptosis, cellular proliferation, differentiation, and other important cellular processes, their deregulation is important for the development of a wide range of diseases including cancer. Apart from tissue, specific disease-related miRNA signatures can be found in body fluids as well. Especially for urologic diseases or injuries, urine miRNAs represent a promising group of biomarkers. Despite a large number of studies describing the importance of urinary miRNAs, there is a lack of recommendations for urine management and subsequent miRNA analysis. Thus, in this chapter, we aim to describe the origin and functions of urinary miRNAs and discuss the technical aspects of their detection including the pre-analytical phase principles and new directions in quantification, which could forward urine miRNA into clinical practice.
- MeSH
- Urinalysis methods MeSH
- Biomarkers analysis urine MeSH
- Humans MeSH
- MicroRNAs analysis isolation & purification urine MeSH
- Polymerase Chain Reaction methods MeSH
- RNA Stability MeSH
- Urologic Diseases diagnosis urine MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Východiska: V současnosti nejsou klinicky využitelné tumorové markery založené na analýze moči, které by byly dostatečně citlivé a specifické, aby nahradily cystoskopii v detekci karcinomu močového měchýře (bladder cancer – BCA). Jednou z možností jsou močové mikroRNA (miRNA) představující novou skupinu biomarkerů pro časnou a neinvazivní diagnostiku urologických malignit. Soubor pacientů a metody: Do studie bylo zařazeno 155 pacientů s BCA a 83 zdravých kontrol. Expresní profily močových miRNA byly identifikovány za použití Affymetrix miRNA microarrays. Kandidátní miRNA byly dále validovány na nezávislé kohortě pacientů pomocí specifických TaqMan assays metodou kvantitativní real-time polymerázové řetězové reakce. Výsledky: Globální profilování genové exprese odhalilo panel miRNA, které byly významně rozdílně exprimovány u pacientů s BCA ve srovnání se zdravými kontrolami (p < 0,01). V rámci validační fáze byla u tří miRNA potvrzena významně vyšší koncentrace v moči pacientů s BCA v porovnání s kontrolními skupinami (p < 0,0001). Závěr: Identifikovali jsme miRNA, jejichž hladina je významně zvýšena v moči pacientů s BCA. Naše data ukazují, že močové miRNA mohou sloužit jako senzitivní a specifické biomarkery pro časnou a neinvazivní detekci BCA.
Background: Currently, there are no urinary-based tumour markers with sufficient sensitivity and specificity to replace cystoscopy in the detection of bladder cancer (BCA). Urinary microRNAs are emerging as clinically useful class of biomarkers for early and non-invasive detection of urologic malignancies. Patients and Methods: In this study, 155 patients with BCA and 83 healthy controls were enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix miRNA microarrays and candidate miRNAs further validated in independent cohort using specific TaqMan assays and quantitative real-time polymerase chain reaction method. Results: Whole-genome profiling identified miRNA signature with significantly different concentrations in urine of BCA compared to controls (p < 0.01). In the independent validation phase of the study, three miRNAs were confirmed to have significantly higher levels in urine of patients with BCA in comparison with control groups (p < 0.0001). In addition, we observed significant decrease in two miRNAs (p < 0.01) concentrations in the urinary samples collected 3 months after surgery compared to pre-operative samples. Conclusion: We identified and validated miRNAs to have significantly higher concentrations in urine of patients with BCA in comparison with controls. Our data have shown that urinary miRNAs could serve as sensitive and specific biomarkers enabling non-invasive detection of BCA.
- MeSH
- Cohort Studies MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Humans MeSH
- MicroRNAs * urine MeSH
- Biomarkers, Tumor * genetics urine MeSH
- Urinary Bladder Neoplasms * diagnosis genetics urine MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
INTRODUCTION: Currently, there is no accurate diagnostic molecular biomarker for renal cell carcinoma (RCC). The aim of this study was to assess the expression of microRNA-15a (miR-15a) in urine of patients with RCC and to evaluate its potential as a diagnostic molecular biomarker. MATERIALS AND METHODS: In total, 67 patients with solid renal tumors were enrolled: clear-cell RCC (ccRCC, n = 22), papillary RCC (pRCC, n = 16), chromophobe RCC (chRCC, n = 14), oncocytoma (n = 8), papillary adenoma (n = 2) and angiomyolipoma (n = 5). MiRNA-15a expression levels measurement in urine were performed using qPCR. Urine of 15 healthy volunteers without kidney pathology was used as control. RESULTS: We observed a difference in mean miR-15a expression values in groups of pre-operative patients with RCC, benign renal tumors and healthy persons (2.50E-01 ± 2.72E-01 vs 1.32E-03 ± 3.90E-03 vs 3.36E-07 ± 1.04E-07 RFU, respectively, p < 0.01). There was no difference in miR-15a expression between ccRCC, pRCC and chRCC (p > 0.05). Direct association between RCC size and miR-15a expression values was obtained (Pearson correlation coefficient-0.873). On the 8th day after nephrectomy, mean expression value in patients with RCC decreased by 99.53% (p < 0.01). MiR-15a expression differentiated RCC from benign renal tumors with 98.1% specificity, 100% sensitivity at a cut-off value of 5.00E-06 RFU, with AUC-0.955. CONCLUSIONS: MiR-15a expression measured in urine may be used as diagnostic molecular biomarker for RCC.
- MeSH
- Adenoma urine MeSH
- Angiomyolipoma urine MeSH
- Carcinoma, Renal Cell diagnosis pathology surgery urine MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs urine MeSH
- Biomarkers, Tumor urine MeSH
- Kidney Neoplasms diagnosis pathology surgery urine MeSH
- Nephrectomy MeSH
- Adenoma, Oxyphilic urine MeSH
- Polymerase Chain Reaction MeSH
- Aged MeSH
- Sensitivity and Specificity MeSH
- Neoplasm Staging MeSH
- Case-Control Studies MeSH
- Tumor Burden MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Urinary microRNAs (miRNAs) are emerging as clinically useful tool for early and non-invasive detection of various types of cancer including bladder cancer (BCA). In this study, 205 patients with BCA and 99 healthy controls were prospectively enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix miRNA microarrays (2578 miRNAs) and candidate miRNAs further validated in independent cohorts using qRT-PCR. Whole-genome profiling identified 76 miRNAs with significantly different concentrations in urine of BCA compared to controls (P < 0.01). In the training and independent validation phase of the study, miR-31-5p, miR-93-5p and miR-191-5p were confirmed to have significantly higher levels in urine of patients with BCA in comparison with controls (P < 0.01). We further established 2-miRNA-based urinary DxScore (miR-93-5p, miR-31-5p) enabling sensitive BCA detection with AUC being 0.84 and 0.81 in the training and validation phase, respectively. Moreover, DxScore significantly differed in the various histopathological subgroups of BCA and decreased post-operatively. In conclusion, we identified and independently validated cell-free urinary miRNAs as promising biomarkers enabling non-invasive detection of BCA.
- MeSH
- Genome-Wide Association Study MeSH
- Adult MeSH
- Genome, Human MeSH
- Carcinoma diagnosis genetics pathology urine MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics urine MeSH
- Biomarkers, Tumor genetics urine MeSH
- Urinary Bladder Neoplasms diagnosis genetics pathology urine MeSH
- Prospective Studies MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Neoplasm Grading MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
INTRODUCTION: Urinary microRNAs (miRNAs) are emerging as a clinically useful tool for early and non-invasive detection of various types of cancer. The aim of this study was to evaluate whether let-7 family miRNAs differ in their urinary concentrations between renal cell carcinoma (RCC) cases and healthy controls. MATERIALS AND METHODS: In the case-control study, 69 non-metastatic clear-cell RCC patients and 36 gender/age-matched healthy controls were prospectively enrolled. Total RNA was purified from cell-free supernatant of the 105 first morning urine specimens. Let-7 family miRNAs were determined in cell-free supernatant using quantitative miRNA real-time reverse-transcription PCR and absolute quantification approach. RESULTS: Concentrations of all let-7 miRNAs (let-7a, let-7b, let-7c, let-7d, let-7e and let-7g) were significantly higher in urine samples obtained from RCC patients compared to healthy controls (P < 0.001; P < 0.001; P = 0.005; P = 0.006; P = 0.015 and P = 0.002, respectively). Subsequent ROC analysis has shown that let-7a concentration possesses good ability to differentiate between cases and controls with area under curve being 0.8307 (sensitivity 71%, specificity 81%). CONCLUSIONS: We have shown that let-7 miRNAs are abundant in the urine samples of patients with clear-cell RCC, and out of six let-7 family members, let-7a outperforms the others and presents promising non-invasive biomarker for the detection of RCC.
- MeSH
- Adult MeSH
- Carcinoma, Renal Cell diagnosis genetics urine MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics urine MeSH
- Biomarkers, Tumor genetics MeSH
- Kidney Neoplasms diagnosis genetics urine MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- ROC Curve MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
MicroRNAs (miRNAs) in urine are examined as potential biomarkers. We examined the urine samples from 70 individuals (45 males, 25 females, mean age 65 years, range 20-84 years). Of the urine donors, 15 were healthy volunteers, 5 were patients with non-cancer diseases, 50 were patients with different stages of bladder cancer. To examine the spectrum of miRNAs in the cell-free fraction of urine, TaqMan Human miRNA Array Card A v.2.1 was used. A set of 30 miRNAs were found that are constantly present in urine supernatants independently of sex, age and health status of the subjects. We compared this set with miRNAs found in plasma, expressed in kidney and genito-urinary tract. Our results indicate that some miRNA could be transferred from the circulation into urine.
- MeSH
- Adult MeSH
- Kidney metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs blood genetics urine MeSH
- Young Adult MeSH
- Biomarkers, Tumor blood genetics urine MeSH
- Urinary Bladder Neoplasms diagnosis genetics MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Keywords
- qPCR, neinvazivní markery, supernatant,
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs * classification urine MeSH
- Biomarkers, Tumor * urine MeSH
- Urinary Bladder Neoplasms * diagnosis MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Research MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: In this study, we aimed to identify microRNA from urine of multiple myeloma patients that could serve as a biomarker for the disease. RESULTS: Analysis of urine samples was performed using Serum/Plasma Focus PCR MicroRNA Panel (Exiqon) and verified using individual TaqMan miRNA assays for qPCR. We found 20 deregulated microRNA (p < 0.05); for further validation, we chose 8 of them. Nevertheless, only differences in expression levels of miR-22-3p remained close to statistical significance. CONCLUSIONS: Our preliminary results did not confirm urine microRNA as a potential biomarker for multiple myeloma.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs genetics urine MeSH
- Multiple Myeloma diagnosis genetics urine MeSH
- Biomarkers, Tumor urine MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Gene Expression Profiling methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
MicroRNAs (miRNAs) are small noncoding RNAs that posttranscriptionally regulate gene expression. In the last decade, number of evidences showing miRNAs contribution to the regulation of apoptosis, cellular proliferation, differentiation, and other important cellular processes is constantly growing. Specific miRNA expression signatures have been identified in variety of human cancers as well as pathologies of cardiovascular and urinary systems. Our chapter focuses on the potential of urinary miRNAs to serve as biomarkers in uro-oncology, nephrology, and cardiology. We discuss in detail recent knowledge about the origin of urinary miRNAs, their stability, quality control, and their utility as a potential new class of biomarkers in medicine. Finally, we summarize the studies focusing on detection and characterization of urinary miRNAs as potential biomarkers in urologic cancers, nephrology, and cardiology.
- MeSH
- Biomarkers urine MeSH
- Humans MeSH
- MicroRNAs genetics urine MeSH
- Neoplasms diagnosis genetics pathology urine MeSH
- Heart Diseases diagnosis genetics pathology urine MeSH
- RNA Stability MeSH
- Urologic Diseases diagnosis genetics pathology urine MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
