title: A molecular signature predictive of indolent prostate cancer.
abstract: Many newly diagnosed prostate cancers present as low Gleason score tumors that require no treatment intervention. Distinguishing the many indolent tumors from the minority of lethal ones remains a major clinical challenge. We now show that low Gleason score prostate tumors can be distinguished as indolent and aggressive subgroups on the basis of their expression of genes associated with aging and senescence. Using gene set enrichment analysis, we identified a 19-gene signature enriched in indolent prostate tumors. We then further classified this signature with a decision tree learning model to identify three genes--FGFR1, PMP22, and CDKN1A--that together accurately predicted outcome of low Gleason score tumors. Validation of this three-gene panel on independent cohorts confirmed its independent prognostic value as well as its ability to improve prognosis with currently used clinical nomograms. Furthermore, protein expression of this three-gene panel in biopsy samples distinguished Gleason 6 patients who failed surveillance over a 10-year period. We propose that this signature may be incorporated into prognostic assays for monitoring patients on active surveillance to facilitate appropriate courses of treatment.
authors.affiliation: Department of Urology, Columbia University Medical Center, New York, NY 10029, USA.
authors.forename: Shazia
authors.initials: S
authors.lastname: Irshad
authors.forename: Mukesh
authors.initials: M
authors.lastname: Bansal
authors.forename: Mireia
authors.initials: M
authors.lastname: Castillo-Martin
authors.forename: Tian
authors.initials: T
authors.lastname: Zheng
authors.forename: Alvaro
authors.initials: A
authors.lastname: Aytes
authors.forename: Sven
authors.initials: S
authors.lastname: Wenske
authors.forename: Clémentine
authors.initials: C
authors.lastname: Le Magnen
authors.forename: Paolo
authors.initials: P
authors.lastname: Guarnieri
authors.forename: Pavel
authors.initials: P
authors.lastname: Sumazin
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Benson
authors.forename: Michael M
authors.initials: MM
authors.lastname: Shen
authors.forename: Andrea
authors.initials: A
authors.lastname: Califano
authors.forename: Cory
authors.initials: C
authors.lastname: Abate-Shen
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics / Q000473:pathology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D003663:Decision Trees; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D013045:Species Specificity
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
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