Xiaoyi Huang1, Tiezheng Yuan2, Meihua Liang3, Meijun Du2, Shu Xia4, Rachel Dittmar2, Dian Wang5, William See6, Brian A Costello7, Fernando Quevedo7, Winston Tan8, Debashis Nandy7, Graham H Bevan9, Sherri Longenbach7, Zhifu Sun10, Yan Lu11, Tao Wang12, Stephen N Thibodeau13, Lisa Boardman7, Manish Kohli14, Liang Wang15. 1. Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA; Biotherapy Center, Third Affiliated Hospital of Harbin Medical University, Harbin, China. 2. Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA. 3. Department of Endocrinology, Second Affiliated Hospital of Harbin Medical University, Harbin, China. 4. Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 5. Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. 6. Department of Urology, Medical College of Wisconsin, Milwaukee, WI, USA. 7. Department of Oncology, Mayo Clinic, Rochester, MN, USA. 8. Department of Oncology, Mayo Clinic, Jacksonville, FL, USA. 9. University of Rochester Medical Center, Rochester, NY, USA. 10. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA. 11. Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA. 12. Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA. 13. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 14. Department of Oncology, Mayo Clinic, Rochester, MN, USA. Electronic address: kohli.manish@mayo.edu. 15. Department of Pathology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: liwang@mcw.edu.
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.
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 cancerpatients. 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.
Authors: Daniel C Danila; Glenn Heller; Gretchen A Gignac; Rita Gonzalez-Espinoza; Aseem Anand; Erika Tanaka; Hans Lilja; Lawrence Schwartz; Steven Larson; Martin Fleisher; Howard I Scher Journal: Clin Cancer Res Date: 2007-12-01 Impact factor: 12.531
Authors: Jan C Brase; Marc Johannes; Thorsten Schlomm; Maria Fälth; Alexander Haese; Thomas Steuber; Tim Beissbarth; Ruprecht Kuner; Holger Sültmann Journal: Int J Cancer Date: 2011-02-01 Impact factor: 7.396
Authors: Lisa M McShane; Douglas G Altman; Willi Sauerbrei; Sheila E Taube; Massimo Gion; Gary M Clark Journal: J Natl Cancer Inst Date: 2005-08-17 Impact factor: 13.506
Authors: Marc R Friedländer; Sebastian D Mackowiak; Na Li; Wei Chen; Nikolaus Rajewsky Journal: Nucleic Acids Res Date: 2011-09-12 Impact factor: 16.971
Authors: Martina Redova; Alexandr Poprach; Jana Nekvindova; Robert Iliev; Lenka Radova; Radek Lakomy; Marek Svoboda; Rostislav Vyzula; Ondrej Slaby Journal: J Transl Med Date: 2012-03-22 Impact factor: 5.531
Authors: R J Bryant; T Pawlowski; J W F Catto; G Marsden; R L Vessella; B Rhees; C Kuslich; T Visakorpi; F C Hamdy Journal: Br J Cancer Date: 2012-01-12 Impact factor: 7.640
Authors: Johann S de Bono; Howard I Scher; R Bruce Montgomery; Christopher Parker; M Craig Miller; Henk Tissing; Gerald V Doyle; Leon W W M Terstappen; Kenneth J Pienta; Derek Raghavan Journal: Clin Cancer Res Date: 2008-10-01 Impact factor: 12.531
Authors: Johan Skog; Tom Würdinger; Sjoerd van Rijn; Dimphna H Meijer; Laura Gainche; Miguel Sena-Esteves; William T Curry; Bob S Carter; Anna M Krichevsky; Xandra O Breakefield Journal: Nat Cell Biol Date: 2008-11-16 Impact factor: 28.824