Integrative functional genetic-epigenetic approach for selecting genes as urine biomarkers for bladder cancer diagnosis.

Early screening for bladder cancer (BC) holds the key to combat and control the increasing global burden of BC mortality. We presented a simple approach to characterize, analyze, and validate a panel of biomarkers in BC and their relationship to bilharziasis. We investigated voided urine and blood samples from patients with bladder cancer (n = 94), benign bladder lesions (n = 60), and age-matched normal controls (n = 56). This study was divided into the following phases. (1) We analyzed the expression of urinary Hyaluronoglucosaminidase 1 (HYAL1) protein in BC and control samples by zymography. (2) We performed bioinformatics analysis to retrieve a set of epigenetic regulators of HYAL1. (3) This set of three selected genes [long non-coding RNA-urothelial cancer associated 1(lncRNA-UCA1), microRNA-210, and microRNA-96] was then analyzed in the same urine samples used in phase I by quantitative real-time PCR. (4) A high reproducibility of gene selection results was also determined from statistical validation. The urinary expression of HYAL1 protein and its epigenetic regulators were higher in BC patients (P < .001). The receiver-operating characteristic curve analyses demonstrated that each one had good sensitivity and specificity for distinguishing BC patients from non-BC ones (HYAL1, 89.4 and 91.2 %; miR-210, 76.6 and 93 %; miR-96, 76.6 and 89.4 %; and lncRNA-UCA1, 91.5 and 96.5 %). There was a significant positive correlation between HYAL1 and the selected epigenetic biomarkers. The performance of this urine biomarker panel reached 100 % sensitivity and 89.5 % specificity for bladder cancer diagnosis.

Rapid detection of urinary long non-coding RNA urothelial carcinoma associated one using a PCR-free nanoparticle-based assay.

We developed a specific hybridization assay for direct detection of long non-coding RNA urothelial carcinoma associated-1 (lncRNA-UCA1). Total RNA was extracted from urine pellet samples (bladder carcinoma patients and controls). Then, we compared the developed nanoassay with quantitative real time polymerase chain reaction (qRT-PCR) results in detection of urine UCA1 in bladder cancer and control samples. The sensitivity and the specificity of UCA1 nanoassay were 92.1% and 93.3%, respectively. The concordance of the two methods was 98%. Interestingly, all bilharzial benign cases showed negative lncRNA-UCA1 using both methods. UCA1-nanoassay is a valid test for direct detection of urine UCA1 for bladder cancer detection.

Urine biomarkers of schistosomiais and its associated bladder cancer.

Schistosomiasis (SCH) is the second only to malaria among the parasitic diseases affecting humans regarding the prevalence of infection worldwide. In this nonsystematic review, we summarize the existing data on commercially available and promising investigational urine markers for the detection of SCH and its associated bladder cancer (BC). We searched PubMed, Scopus and Cochran without time limits. We reviewed the recent literatures on urine-based markers for SCH and its associated BC. Many studies identified several urine biomarkers of Schistosoma haematobium and Schistosoma mansoni worms and their associated BC using automated, inexpensive, quantitative assays in urine. These markers may aid in early detection of bladder carcinoma and have the potential to reduce the number of follow-up cystoscopy, thus reducing healthcare costs and patient discomfort, at the same time. Nevertheless, clinical evidence is insufficient to warrant the substitution of the cystoscopic follow-up scheme by any of the currently available urine marker tests.

Evaluation of urinary microRNA panel in bladder cancer diagnosis: relation to bilharziasis.

We assessed the differential expression of a urinary panel of microRNAs (miRs) in terms of potential application as diagnostic markers of bladder cancer (BC) and relationship to bilharziasis. We investigated voided urine samples and blood from patients with BC (n = 188), benign bladder lesions (n = 88), and age-matched controls (n = 92). Five miRs (miR-210, miR-10b, miR-29c, miR-221, and miR-23a) were selected from previous microarray signature profiling (released by miR2Disease). Afterward, they were validated using polymerase chain reaction array. The expression levels of miR-210, miR-10b, and miR-29c in the urine samples were significantly higher in BC (P < 0.001). The receiver-operating characteristic curve analyses demonstrated that each miR had good sensitivity and specificity for distinguishing patients with BC from patients without BC (miR-210, 71.3% and 91.1%; miR-10b, 80.9% and 91.1%; and miR-183, 71.3% and 88.9%). On combining the 3 miR detection data with the urinary cytology, the results sensitivity increased to 95.2%. Relative quantity mean rank of the miR-29c was significantly higher in the bilharzial-positive patients compared with bilharzial-negative patients. To conclude, urine miR-210, miR-10b, and miR-29c are promising tumor markers for BC: bilharzial and nonbilharzial.

MicroRNA-10b and minichromosome maintenance complex component 5 gene as prognostic biomarkers in breast cancer.

The aim of this study is to identify micro-ribonucleic acid (microRNA) and its target, in addition to their relationship to the outcome in breast cancer (BC). To achieve this aim, we investigated microRNA-10b (miR-10b) and minichromosome maintenance complex component 5 (MCM5 mRNA) expression in 230 breast tissue samples by real-time PCR and semiquantitative conventional RT-PCR, respectively. Relapse-free survival (RFS) associated with miRNA-10b and MCM5 mRNA were tested by Kaplan-Meier survival analysis. The impact of miRNA-10b andMCM5 mRNA expression on the survival was evaluated by Cox proportional hazard regression model. The expression of miRNA-10b and MCM5 mRNA was positive in 86.4 and 79.7 % breast cancer patients, respectively. The overall concordance rate between miRNA-10b and MCM5 RNA was 90.4 %. The median follow-up period was 50 months. The survival analysis showed that high levels of both miR-10b and MCM5 were associated with short relapse free survival of BC. We identified MCM5 mRNA expression changes consistent with the miRNA-10b target regulation. Thus, we could consider miRNA-10b and MCM5 mRNA as prognostic markers and potential therapeutic targets in breast cancer to be applied to other patient data sets.