Most cited article - PubMed ID 24035473
Urine microRNAs as potential noninvasive biomarkers in urologic cancers
Current routine screening methods for the diagnosis of prostate cancer (PCa) have significantly increased early detection of the disease but often show unsatisfactory analytical parameters. A class of promising markers represents urinary microRNAs (miRNAs). In the last five years, there has been an extensive increase in the number of studies on this topic. Thus, this review aims to update knowledge and point out technical aspects affecting urinary miRNA analysis. The review of relevant literature was carried out by searching the PubMed database for the keywords: microRNA, miRNA, urine, urinary, prostate cancer, and diagnosis. Papers discussed in this review were retrieved using PubMed, and the search strategy was as follows: (urine OR urinary) WITH (microRNA OR miRNA) AND prostate cancer. The search was limited to the last 5 years, January 2017 to December 2021. Based on the defined search strategy, 31 original publications corresponding to the research topic were identified, read and reviewed to present the latest findings and to assess possible translation of urinary miRNAs into clinical practice. Reviews or older publications were read and cited if they valuably extended the context and contributed to a better understanding. Urinary miRNAs are potentially valuable markers for the diagnosis of prostate cancer. Despite promising results, there is still a need for independent validation of exploratory data, which follows a strict widely accepted methodology taking into account the shortcomings and factors influencing the analysis.
- Keywords
- diagnosis, extracellular vesicles, microRNA, prostate cancer, urine,
- Publication type
- Journal Article MeSH
- Review 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.
- Keywords
- biomarker, bladder cancer, cell-free miRNAs, non-invasive diagnosis, urine,
- 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
- Names of Substances
- MicroRNAs MeSH
- MIRN191 microRNA, human MeSH Browser
- MIRN31 microRNA, human MeSH Browser
- MIRN93 microRNA, human MeSH Browser
- Biomarkers, Tumor 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.
- Keywords
- diagnostic biomarker, let-7, renal cell carcinoma, urine microRNAs,
- 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
- Names of Substances
- MicroRNAs MeSH
- mirnlet7 microRNA, human MeSH Browser
- Biomarkers, Tumor 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
- Names of Substances
- MicroRNAs MeSH
- Biomarkers, Tumor MeSH
Background. Sunitinib is a tyrosine kinase inhibitor used in the treatment of metastatic renal cell carcinoma. The main difficulty related to the treatment is the development of drug resistance followed by rapid progression of the disease. We analyzed tumor tissue of sunitinib treated patients in order to find miRNAs associated with therapeutic response. Methods. A total of 79 patients with metastatic renal cell carcinoma were included in our study. miRNA profiling in tumor tissue samples was performed by TaqMan Low Density Arrays and a group of selected miRNAs (miR-155, miR-374-5p, miR-324-3p, miR-484, miR-302c, and miR-888) was further validated by qRT-PCR. Normalized data were subjected to ROC and Kaplan-Meier analysis. Results. We reported decreased tissue levels of miR-155 and miR-484 as significantly associated with increased time to progression (miR-155: median TTP 5.8 versus 12.8 months, miR-484: median TTP 5.8 versus 8.9 months). Conclusion. miR-155 and miR-484 are potentially connected with sunitinib resistance and failure of the therapy. miR-155 is a known oncogene with direct influence on neovascularization. Biological role of miR-484 has to be clarified. Stratification of patients based on miRNA analysis would allow more personalized approach in therapy of metastatic renal cell carcinoma.
- MeSH
- Adult MeSH
- Indoles administration & dosage MeSH
- Kaplan-Meier Estimate MeSH
- Carcinoma, Renal Cell drug therapy genetics pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- MicroRNAs biosynthesis genetics MeSH
- Biomarkers, Tumor biosynthesis genetics MeSH
- Neovascularization, Pathologic drug therapy genetics pathology MeSH
- Disease Progression MeSH
- Pyrroles administration & dosage MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Sunitinib 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
- Names of Substances
- Indoles MeSH
- MicroRNAs MeSH
- MIRN155 microRNA, human MeSH Browser
- MIRN484 microRNA, human MeSH Browser
- Biomarkers, Tumor MeSH
- Pyrroles MeSH
- Sunitinib MeSH