Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients
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Prashant K. Singh1, Leah Preus2, Qiang Hu3, Li Yan3, Mark D. Long1, Carl D. Morrison4, Mary Nesline2, Candace S. Johnson1, Shahriar Koochekpour5, Manish Kohli6, Song Liu3, Donald L. Trump7, Lara E Sucheston-Campbell2,* and Moray J. Campbell1,*
1 Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY
2 Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY
3 Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY
4 Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY
5 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY
6 Department of Medical Oncology, Mayo Clinic, Rochester, MN
7 Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY
* The authors share position as senior and corresponding authors
Moray J. Campbell, email:
Lara E Sucheston-Campbell, email:
Keywords: Prostate cancer, microRNA, biochemical progression, miR-103, miR-125b, miR-222, cancer epigenetics
Received: January 13, 2014 Accepted: February 13, 2014 Published: February 13, 2014
We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p<.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.
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