A novel combined miRNA and methylation marker panel (miMe) for prediction of prostate cancer outcome after radical prostatectomy

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DOI

  • Siri H Strand
  • ,
  • Elham Bavafaye-Haghighi
  • ,
  • Helle Kristensen, Exiqon ⁻ a Qiagen company, Skelstedet 16, 2950 Vedbæk, Denmark. mouritzenpeter0@gmail.com.
  • ,
  • Anne K Rasmussen, Exiqon ⁻ a Qiagen company, Skelstedet 16, 2950 Vedbæk, Denmark. mouritzenpeter0@gmail.com.
  • ,
  • Soren Hoyer
  • ,
  • Michael Borre
  • Peter Mouritzen, Exiqon ⁻ a Qiagen company, Skelstedet 16, 2950 Vedbæk, Denmark. mouritzenpeter0@gmail.com.
  • ,
  • Soren Besenbacher
  • Torben F Orntoft
  • Karina D Sorensen

Improved prognostic biomarkers are needed to guide personalized prostate cancer (PC) treatment decisions. Due to the prominent molecular heterogeneity of PC, multimarker panels may be more robust. Here, 25 selected top-candidate miRNA and methylation markers for PC were profiled by qPCR in malignant radical prostatectomy (RP) tissue specimens from 198 PC patients (Cohort 1, training). Using GLMnet, we trained a novel multimarker model (miMe) comprising nine miRNAs and three methylation markers that predicted postoperative biochemical recurrence (BCR) independently of the established clinicopathological CAPRA-S nomogram in Cox multivariate regression analysis in Cohort 1 (HR [95% CI]: 1.53 [1.26-1.84], p < 0.001). This result was successfully validated in two independent RP cohorts (Cohort 2, n = 159: HR [95% CI]: 1.35 [1.06-1.73], p = 0.015. TCGA, n = 350: HR [95% CI]: 1.34 [1.01-1.77], p = 0.04). Notably, in CAPRA-S low-risk patients, a high miMe score was associated with >6 times higher risk of BCR, suggesting that miMe may help identify PC patients at high risk of progression despite favorable clinicopathological factors postsurgery. Finally, miMe was a significant predictor of cancer-specific survival (p = 0.019, log-rank test) in a merged analysis of 357 RP patients. In conclusion, we trained, tested and validated a novel 12-marker panel (miMe) that showed significant independent prognostic value in three RP cohorts. In the future, combining miMe score with existing clinical nomograms may improve PC risk stratification and thus help guide treatment decisions.

Original languageEnglish
JournalInternational Journal of Cancer
Volume145
Issue12
Pages (from-to)3445-3452
ISSN0020-7136
DOIs
Publication statusPublished - 2019

    Research areas

  • DNA methylation, biomarkers, microRNA, prognosis, prostate cancer

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