Detection of circulatory microRNAs in prostate cancer.

Prostate cancer (PCa) is one of the most common cancer worldwide and accounts for 14.4 % of all new cancer cases. The clinical outcome and management of PCa can be significantly improved by use of biomarker assays for early detection, prognosis and also for prediction and monitoring of treatment response. MiRNAs are short, endogenous, single-stranded RNA molecules that play important role in regulation of gene expression and can modulate a number of cellular processes. Discovery of miRNAs in circulation has not only facilitated understanding their role in various diseases but also paved new avenues for biomarker discovery due to their ease of access and stability. The fact that a minimally invasive test based on miRNAs profiles can distinguish the presence or absence of disease illustrates immense potential of these molecules as predictive biomarkers.In this chapter, we have summarized the presumed mechanisms of miRNA release into the circulation and systematically summarized the studies of circulatory miRNAs in PCa. Also, we have mainly focused on the methodology of identification of circulatory miRNAs from biofluids.

Circulatory miR-628-5p is downregulated in prostate cancer patients.

Prostate cancer (PCa) is a major health concern for men in the USA. Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of various cancers, including PCa. Circulatory forms of miRNAs have been detected in serum and hold promise as minimally invasive cancer biomarkers. This study aimed to identify potential circulatory miRNAs that can provide insights into new mechanisms for clinical diagnosis of PCa and can serve as potential biomarkers and/or therapeutic targets. Candidate serum miRNAs were detected by using PCR microarray in a learning set of six African American (AA) and six Caucasian American (CA) PCa patients. Discriminating performance of candidate miRNAs was validated by qRT-PCR in serum samples from 36 AA (24 PCa patients and 12 controls) and 36 CA (16 PCa patients and 20 controls). From the miRNA profiling experiments, three differentially expressed miRNAs (miR-25, miR-101, and miR-628-5p) were selected for future validation. In the validation set, there was an overall low expression of miR-25 (p < 0.01), miR-101 (p < 0.001), and miR-628-5p (p < 0.0001) in serum of PCa patients as compared with normal individuals. Subdivision on the basis of ethnicity showed that serum expression levels of miR-628-5p were significantly downregulated in both AA and CA PCa patients when compared with their respective controls. Our results demonstrate that the three miRNAs, particularly miR-628-5p, may be further developed as a biomarker, which can serve as novel noninvasive biomarker for PCa diagnosis and prognosis.

MicroRNA profiling in prostate cancer--the diagnostic potential of urinary miR-205 and miR-214.

Prostate cancer (PCa) is the most common type of cancer in men in the United States, which disproportionately affects African American descents. While metastasis is the most common cause of death among PCa patients, no specific markers have been assigned to severity and ethnic biasness of the disease. MicroRNAs represent a promising new class of biomarkers owing to their inherent stability and resilience. In the present study, we investigated potential miRNAs that can be used as biomarkers and/or therapeutic targets and can provide insight into the severity and ethnic biasness of PCa. PCR array was performed in FFPE PCa tissues (5 Caucasian American and 5 African American) and selected differentially expressed miRNAs were validated by qRT-PCR, in 40 (15 CA and 25 AA) paired PCa and adjacent normal tissues. Significantly deregulated miRNAs were also analyzed in urine samples to explore their potential as non-invasive biomarker for PCa. Out of 8 miRNAs selected for validation from PCR array data, miR-205 (p<0.0001), mir-214 (p<0.0001), miR-221(p<0.001) and miR-99b (p<0.0001) were significantly downregulated in PCa tissues. ROC curve shows that all four miRNAs successfully discriminated between PCa and adjacent normal tissues. MiR-99b showed significant down regulation (p<0.01) in AA PCa tissues as compared to CA PCa tissues and might be related to the aggressiveness associated with AA population. In urine, miR-205 (p<0.05) and miR-214 (p<0.05) were significantly downregulated in PCa patients and can discriminate PCa patients from healthy individuals with 89% sensitivity and 80% specificity. In conclusion, present study showed that miR-205 and miR-214 are downregulated in PCa and may serve as potential non-invasive molecular biomarker for PCa.