mRNA Expression Signature of Gleason Grade Predicts Lethal Prostate Cancer
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Author
Penney, Kathryn L.
Sinnott, Jennifer A.
Fall, Katja
Pawitan, Yudi
Hoshida, Yujin
Kraft, Peter
Stark, Jennifer R.
Fiorentino, Michelangelo
Perner, Sven
Finn, Stephen
Calza, Stefano
Flavin, Richard
Freedman, Matthew L.
Setlur, Sunita
Sesso, Howard D.
Andersson, Swen-Olof
Martin, Neil
Kantoff, Philip W.
Johansson, Jan-Erik
Adami, Hans-Olov
Rubin, Mark A.
Loda, Massimo
Golub, Todd R.
Andrén, Ove
Mucci, Lorelei A.
Published Version
https://doi.org/10.1200/JCO.2010.32.6421Metadata
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Penney, Kathryn L., Jennifer A. Sinnott, Katja Fall, Yudi Pawitan, Yujin Hoshida, Peter Kraft, Jennifer R. Stark, et al. 2011. “mRNA Expression Signature of Gleason Grade Predicts Lethal Prostate Cancer.” Journal of Clinical Oncology 29 (17): 2391–96. https://doi.org/10.1200/jco.2010.32.6421.Abstract
Purpose: Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis. Patients and Methods: Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason <= 6 to those with Gleason >= 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases.ResultsWe built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006). Conclusion: Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment. J Clin Oncol 29:2391-2396.Terms of Use
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