Faculty Collaboration Database

Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur Urol 2015 Jan;67(1):33-41

Date

08/19/2014

Pubmed ID

25129854

Pubmed Central ID

PMC4252606

DOI

10.1016/j.eururo.2014.07.035

Scopus ID

2-s2.0-84924372715 (requires institutional sign-in at Scopus site)   519 Citations

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 evaluation 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.

Author List

Huang X, Yuan T, Liang M, Du M, Xia S, Dittmar R, Wang D, See W, Costello BA, Quevedo F, Tan W, Nandy D, Bevan GH, Longenbach S, Sun Z, Lu Y, Wang T, Thibodeau SN, Boardman L, Kohli M, Wang L

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Exosomes
Humans
Kaplan-Meier Estimate
Male
MicroRNAs
Middle Aged
Prognosis
Proportional Hazards Models
Prostatic Neoplasms, Castration-Resistant
Survival Rate