Combination of urinary MiR-501 and MiR-335 with current clinical diagnostic parameters as potential predictive factors of prostate biopsy outcome

Background: The detection of prostate cancer (PCa) is currently based on prostate-specific antigen (PSA) quantification as an initial screening followed by ultrasound-guided transrectal biopsy. However, the high rate of false-negative biopsies often leads to inappropriate treatment. Therefore, new molecular biomarkers, such as urine microRNAs (miRNAs), are a possible way to redefine PCa diagnostics. Patients and Methods: Urine samples of 356 patients undergoing prostate biopsy (256 cases with confirmed prostate cancer, 100 cases with negative prostate biopsy) at the Masaryk Memorial Cancer Institute (Czech Republic) and additional 36 control subjects (healthy controls, benign prostatic hyperplasia – BPH) were divided into the discovery and validation cohorts and analyzed. In the discovery phase, small RNA sequencing was performed using the QIAseq miRNA Library Kit and the NextSeq 500 platform. Identified miRNA candidates were validated by the RT-qPCR method in the independent validation phase. Results: Using the small RNA sequencing method, we identified 12 urine miRNAs significantly dysregulated between PCa patients and controls. Furthermore, independent validation showed the ability of miR-501-3p and the quantitative miR-335:miR-501 ratio to distinguish between PCa patients and patients with negative prostate biopsy. The subsequent combination of the miR-335:miR-501 ratio with PSA and total prostate volume (TPV) using logistic regression exceeded the analytical accuracy of standalone parameters [area under curve (AUC)=0.75, positive predictive value (PPV)=0.85, negative predictive value (NPV)=0.51)] and discriminated patients according to biopsy outcome. Conclusion: Combination of miR-335:miR-501 ratio with PSA and total prostate volume was able to identify patients with negative prostate biopsy and could potentially streamline decision making for biopsy indication

Current Concepts of Non-Coding RNAs in the Pathogenesis of Non-Clear Cell Renal Cell Carcinoma

Renal cell carcinoma (RCC) is a relatively rare malignancy of the urinary tract system. RCC is a heterogenous disease in terms of underlying histology and its associated underlying pathobiology, prognosis and treatment schedule. The most prevalent histological RCC subtype is clear-cell renal cell carcinoma (ccRCC), accounting for about 70-80% of all RCCs. Though the pathobiology and treatment schedule for ccRCC are well-established, non-ccRCC subtypes account for 20%-30% of RCC altogether, and their underlying molecular biology and treatment options are poorly defined. The class of non-coding RNAs-molecules that are generally not translated into proteins-are new cancer drivers and suppressors in all types of cancer. Of these, small non-coding microRNAs (miRNAs) contribute to carcinogenesis by regulating posttranscriptional gene silencing. Additionally, a growing body of evidence supports the role of long non-coding RNAs (lncRNAs) in cancer development and progression. Most studies on non-coding RNAs in RCC focus on clear-cell histology, and there is a relatively limited number of studies on non-ccRCC subtypes. The aim of this review is to give an overview of the current knowledge regarding the role of non-coding RNAs (including short and long non-coding RNAs) in non-ccRCC and to highlight possible implications as diagnostic, prognostic and predictive biomarkers

Detection of let-7 miRNAs in urine supernatant as potential diagnostic approach in non-metastatic clear-cell renal cell carcinoma

IntroductionUrinary 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 methodsIn 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. ResultsConcentrations 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%). ConclusionsWe 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

Non-Coding RNAs as Cancer Hallmarks in Chronic Lymphocytic Leukemia

The discovery of non-coding RNAs (ncRNAs) and their role in tumor onset and progression has revolutionized the way scientists and clinicians study cancers. This discovery opened new layers of complexity in understanding the fine-tuned regulation of cellular processes leading to cancer. NcRNAs represent a heterogeneous group of transcripts, ranging from a few base pairs to several kilobases, that are able to regulate gene networks and intracellular pathways by interacting with DNA, transcripts or proteins. Deregulation of ncRNAs impinge on several cellular responses and can play a major role in each single hallmark of cancer. This review will focus on the most important short and long non-coding RNAs in chronic lymphocytic leukemia (CLL), highlighting their implications as potential biomarkers and therapeutic targets as they relate to the well-established hallmarks of cancer. The key molecular events in the onset of CLL will be contextualized, taking into account the role of the &ldquo;dark matter&rdquo; of the genome

Urinary microRNAs and Their Significance in Prostate Cancer Diagnosis: A 5-Year Update

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

MicroRNA isolation and quantification in cerebrospinal fluid: A comparative methodical study.

Associated with the pathogenesis of many cancers, including brain tumors, microRNAs (miRNAs) present promising diagnostic biomarkers. These molecules have been also studied in cerebrospinal fluid (CSF), showing great potential as a diagnostic tool in patients with brain tumors. Even though there are some biological and technological factors that could affect the results and their biological and clinical interpretation, miRNA analysis in CSF is not fully standardized. This study aims to compare several RNA extraction and miRNA quantification approaches, including high-throughput technologies and individual miRNA detection methods, thereby contributing to the optimization and standardization of quantification of extracellular miRNAs in CSF. Such knowledge is essential for the potential use of miRNAs as diagnostic biomarkers in brain tumors

Utilization and efficacy of second-line targeted therapy in metastatic renal cell carcinoma: data from a national registry

Abstract Background It is well known that patient characteristics and survival outcomes in randomized trials may not necessarily be similar to those in real-life clinical practice. The aim of the present study was to analyse second line treatment strategies in the real-world practice and to estimate the outcomes of patients treated with second-line targeted therapy for metastatic renal cell carcinoma (mRCC). Methods This is a retrospective, registry-based study using data from the national registry of targeted therapies for mRCC. The RENIS registry contains data on 3049 patients who started the therapy with at least one targeted agent before 31 December, 2014. Of these patients, 1029 had a record of at least two different targeted therapies and sufficient data for analysis. Survival analysis was carried out using the Kaplan-Meier method. Statistical significance of differences in survival between subgroups was assessed using the log-rank test. Results The median overall survival from the start of second-line treatment was 17.0 months (95% confidence interval [CI] 14.5–19.5 months), 17.1 months (95% CI 14.5–19.8), and 15.4 months (95% CI 11.0–19.7) for second-line everolimus, sorafenib, and sunitinib, respectively. Patients receiving second-line everolimus were older at the start of second-line treatment, more likely to have metachronous disease, and less likely to be previously treated with cytokines or to continue to third-line treatment than patients treated with second-line sunitinib or sorafenib. Progression-free survival (PFS) correlated with PFS on first-line treatment only for everolimus. Conclusions In this retrospective study, no significant differences in survival were observed between the cohorts treated with different second-line agents including everolimus, sorafenib, and sunitinib