title: Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients.
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.
authors.affiliation: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Singh
authors.forename: Leah
authors.initials: L
authors.lastname: Preus
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Mark D
authors.initials: MD
authors.lastname: Long
authors.forename: Carl D
authors.initials: CD
authors.lastname: Morrison
authors.forename: Mary
authors.initials: M
authors.lastname: Nesline
authors.forename: Candace S
authors.initials: CS
authors.lastname: Johnson
authors.forename: Shahriar
authors.initials: S
authors.lastname: Koochekpour
authors.forename: Manish
authors.initials: M
authors.lastname: Kohli
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.forename: Donald L
authors.initials: DL
authors.lastname: Trump
authors.forename: Lara E
authors.initials: LE
authors.lastname: Sucheston-Campbell
authors.forename: Moray J
authors.initials: MJ
authors.lastname: Campbell
mesh_terms: D045744:Cell Line, Tumor; D018450:Disease Progression; D057890:Epigenomics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D017211:Treatment Failure
chemical_list: D035683:MicroRNAs