Exosomal miR-1290 and miR-375 as Prognostic Markers in Castration-resistant Prostate Cancer

Abstract

Background Extracellular microRNAs (miRNAs) embedded in circulating exosomes may serves as prognostic biomarkers in cancer. Objective To identify and evaluate plasma exosomal miRNAs for prognosis in castration-resistant prostate cancer (CRPC). Design, setting, and participants RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for prognosis using quantitative real-time polymerase chain reaction in a follow-up cohort of 100 CRPC patients. Outcome measurements and statistical analysis Cox regression and Kaplan-Meier survival analyses were used to evaluate survival association using candidate miRNAs along with clinical prognostic factors. Results and limitations RNA sequencing in screening cohort generated approximately 6.80 million mappable reads per patient. Of those with normalized read counts ≥5, 43% were mapped to miRNAs for a total of 375 known and 57 novel miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and -375 with overall survival (false discover rate <0.05). Of those, higher levels of miR-1290 and -375 were significantly associated with poor overall survival (p < 0.004) in the follow-up cohort. Incorporation of miR-1290/-375 into putative clinical prognostic factors-based models in CRPC stage significantly improved predictive performance with a time-dependent area under the curve increase from 0.66 to 0.73 (p = 6.57 × 10−6). Conclusions Plasma exosomal miR-1290 and miR-375 are promising prognostic biomarkers for CRPC patients. Prospective validation is needed for further development of these candidate miRNAs. Patient summary In this study, we evaluated whether small RNAs circulating in blood could be used to predict clinical outcomes in late-stage prostate cancer patients. We identified two blood-based small RNAs whose levels showed significant association with survival. Our results warrant further investigation because the noninvasive blood-based test has great potential in the management of late-stage prostate cancer.

Detection and quantification of extracellular microRNAs in medulloblastoma

“…[29] Ex-miRNAs can transfer their oncogenic activity to recipient target cells to infl uence cancer stimulatory activities, thus contributing to the formation of a pre-metastatic niche and promotion of metastasis. [28,30] This exchange of miRNAs between primary tumors and target cells is an interesting and novel dimension to the regulation of a cell phenotype [31][32][33][34] and may be particularly important in cancers that have a propensity for dissemination, such as MB. MB includes various subtypes with group 3 and 4 subtypes being clinically distinct with regard to metastasis and prognosis, which may also manifest in a difference in their miRNA spectra.…”

Exosomes in semen: opportunities as a new tool in prostate cancer diagnosis

“…Despite tests on blood samples already developed, the advantage of collecting EVs from urine is the enrichment in prostasomes rather than other constituents. The presence of prostatic fluid into urine and prostasomes in EVs fractions isolated from urine was confirmed by detection of prostate-specific proteins like prostate-specific membrane antigen (PSMA), prostatic acid phosphatase, and prostate transglutaminase (62)(63)(64)(65). In a recent study, protein compositions of EVs, isolated from preoperative urine samples of PCa patients was compared to the samples of healthy individuals.…”

The translational potential of microRNAs as biofluid markers of urological tumours

“…88 (Table 3) report more promising diagnostic and prognostic data than earlier studies. One reason for this improvement could be that combinations of different miRNAs 111,121 , miRNAs in combination with other markers 113,120 and miRNAs in blood cells 123 or exosomes 124 were investigated, rather than single miRNAs. However, the promising results of these studies are yet to be validated.…”