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Platinum Priority – Prostate Cancer
Editorial by Benedikta S. Haflidadóttir and Yvonne Ceder on pp. 42–43 of this issue

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

By: Xiaoyi Huang a b , Tiezheng Yuan a , Meihua Liang c , Meijun Du a , Shu Xia a d , Rachel Dittmar a , Dian Wang e , William See f , Brian A. Costello g , Fernando Quevedo g , Winston Tan h , Debashis Nandy g , Graham H. Bevan i , Sherri Longenbach g , Zhifu Sun j , Yan Lu k , Tao Wang l , Stephen N. Thibodeau m , Lisa Boardman g , Manish Kohli g lowast and Liang Wang a lowast

European Urology, Volume 67 Issue 1, January 2015, Pages 33-41

Published online: 01 January 2015

Keywords: Exosome, microRNA, Extracellular RNA, RNA sequencing, Prostate cancer, Biomarker, Prognosis, Survival

Abstract Full Text Full Text PDF (2,6 MB) Patient Summary

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.

Take Home Message

We identified and verified two exosomal microRNAs (miRNAs) showing a significant association with overall survival in castration-resistant prostate cancer patients. The blood-based extracellular miRNA test is noninvasive and has great potential to serve as a prognostic biomarker for late-stage prostate cancer.

Keywords: Exosome, microRNA, Extracellular RNA, RNA sequencing, Prostate cancer, Biomarker, Prognosis, Survival.

Footnotes

a Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA

b Biotherapy Center, Third Affiliated Hospital of Harbin Medical University, Harbin, China

c Department of Endocrinology, Second Affiliated Hospital of Harbin Medical University, Harbin, China

d Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

e Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

f Department of Urology, Medical College of Wisconsin, Milwaukee, WI, USA

g Department of Oncology, Mayo Clinic, Rochester, MN, USA

h Department of Oncology, Mayo Clinic, Jacksonville, FL, USA

i University of Rochester Medical Center, Rochester, NY, USA

j Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

k Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

l Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA

m Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

lowast Corresponding authors. Liang Wang: Department of Pathology and MCW Cancer Center, Medical College of Wisconsin, 8701 W. Watertown Plank Road, TRBC #C4678, Milwaukee, WI 53226, USA. Tel. +1 414 955 2574; Manish Kohli: Division of Medical Oncology, Department of Oncology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA. Tel. +1 507 284 3903.

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