Abstract
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.
Highlights
In men in the USA and elsewhere, prostate cancer (CaP) is the most common noncutaneous cancer diagnosed and second leading cause of death [1, 2]
LNCaP vs LNCaP-C4-2 revealed 16 miRNAs that were significantly up-regulated and 3 miRNAs were down-regulated in LNCaP-C4-2
These analyses revealed a significant correlation between expression patterns identified by the cell line and primary tumor analyses
Summary
In men in the USA and elsewhere, prostate cancer (CaP) is the most common noncutaneous cancer diagnosed and second leading cause of death [1, 2]. The prostate-specific antigen (PSA) [3, 4] test has significantly increased cancer detection but has poor specificity and prognostic accuracy. The result of this ambiguity is that, amongst www.impactjournals.com/oncotarget men who have undergone initial therapy, it is uncertain who will relapse with recurrent aggressive disease [5, 6]. These ambiguities are clinically relevant because men who experience treatment failure have a significantly increased risk of dying of CaP [7]. A similar difficulty exists over the accurate identification of indolent disease, in which either radical surgery or high dose radiation treatments could be deferred [1, 2]
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