Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer

Xiaoyi Huang, Tiezheng Yuan, Meihua Liang, Meijun Du, Shu Xia, Rachel Dittmar, Dian Wang, William See, Brian Costello, Fernando Quevedo, Winston Tan, Debashis Nandy, Graham H. Bevan, Sherri Longenbach, Zhifu D Sun, Yan Lu, Tao Wang, Stephen N Thibodeau, Lisa Allyn Boardman, Manish Kohli & 1 others Liang Wang

Research output: Contribution to journalArticle

206 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalEuropean Urology
Volume67
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Castration
MicroRNAs
Prostatic Neoplasms
Survival
RNA Sequence Analysis
Regression Analysis
RNA
Exosomes
Kaplan-Meier Estimate
Hematologic Tests
Survival Analysis
Tumor Biomarkers
Area Under Curve
Real-Time Polymerase Chain Reaction
Biomarkers

Keywords

  • Biomarker
  • Exosome
  • Extracellular RNA
  • microRNA
  • Prognosis
  • Prostate cancer
  • RNA sequencing
  • Survival

ASJC Scopus subject areas

  • Urology

Cite this

Huang, X., Yuan, T., Liang, M., Du, M., Xia, S., Dittmar, R., ... Wang, L. (2015). Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. European Urology, 67(1), 33-41. https://doi.org/10.1016/j.eururo.2014.07.035

Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. / Huang, Xiaoyi; Yuan, Tiezheng; Liang, Meihua; Du, Meijun; Xia, Shu; Dittmar, Rachel; Wang, Dian; See, William; Costello, Brian; Quevedo, Fernando; Tan, Winston; Nandy, Debashis; Bevan, Graham H.; Longenbach, Sherri; Sun, Zhifu D; Lu, Yan; Wang, Tao; Thibodeau, Stephen N; Boardman, Lisa Allyn; Kohli, Manish; Wang, Liang.

In: European Urology, Vol. 67, No. 1, 01.01.2015, p. 33-41.

Research output: Contribution to journalArticle

Huang, X, Yuan, T, Liang, M, Du, M, Xia, S, Dittmar, R, Wang, D, See, W, Costello, B, Quevedo, F, Tan, W, Nandy, D, Bevan, GH, Longenbach, S, Sun, ZD, Lu, Y, Wang, T, Thibodeau, SN, Boardman, LA, Kohli, M & Wang, L 2015, 'Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer', European Urology, vol. 67, no. 1, pp. 33-41. https://doi.org/10.1016/j.eururo.2014.07.035
Huang, Xiaoyi ; Yuan, Tiezheng ; Liang, Meihua ; Du, Meijun ; Xia, Shu ; Dittmar, Rachel ; Wang, Dian ; See, William ; Costello, Brian ; Quevedo, Fernando ; Tan, Winston ; Nandy, Debashis ; Bevan, Graham H. ; Longenbach, Sherri ; Sun, Zhifu D ; Lu, Yan ; Wang, Tao ; Thibodeau, Stephen N ; Boardman, Lisa Allyn ; Kohli, Manish ; Wang, Liang. / Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. In: European Urology. 2015 ; Vol. 67, No. 1. pp. 33-41.
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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.",
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T1 - Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer

AU - Huang, Xiaoyi

AU - Yuan, Tiezheng

AU - Liang, Meihua

AU - Du, Meijun

AU - Xia, Shu

AU - Dittmar, Rachel

AU - Wang, Dian

AU - See, William

AU - Costello, Brian

AU - Quevedo, Fernando

AU - Tan, Winston

AU - Nandy, Debashis

AU - Bevan, Graham H.

AU - Longenbach, Sherri

AU - Sun, Zhifu D

AU - Lu, Yan

AU - Wang, Tao

AU - Thibodeau, Stephen N

AU - Boardman, Lisa Allyn

AU - Kohli, Manish

AU - Wang, Liang

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - Biomarker

KW - Exosome

KW - Extracellular RNA

KW - microRNA

KW - Prognosis

KW - Prostate cancer

KW - RNA sequencing

KW - Survival

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