PLoS ONE (Jan 2015)

A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

  • Erica Hlavin Bell,
  • Simon Kirste,
  • Jessica L Fleming,
  • Petra Stegmaier,
  • Vanessa Drendel,
  • Xiaokui Mo,
  • Stella Ling,
  • Denise Fabian,
  • Isabel Manring,
  • Cordula A Jilg,
  • Wolfgang Schultze-Seemann,
  • Maureen McNulty,
  • Debra L Zynger,
  • Douglas Martin,
  • Julia White,
  • Martin Werner,
  • Anca L Grosu,
  • Arnab Chakravarti

DOI
https://doi.org/10.1371/journal.pone.0118745
Journal volume & issue
Vol. 10, no. 3
p. e0118745

Abstract

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To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy.Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence.Eighty eight miRNAs were identified to be significantly (p36 months). Nine miRNAs were identified to be significantly (p<0.05) associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC) was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone.miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further validation studies.