uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
mRNA Expression Signature of Gleason Grade Predicts Lethal Prostate Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Show others and affiliations
2011 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 29, no 17, 2391-2396 p.Article in journal (Refereed) Published
Abstract [en]

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. Results We 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.

Place, publisher, year, edition, pages
2011. Vol. 29, no 17, 2391-2396 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-258985DOI: 10.1200/JCO.2010.32.6421ISI: 000291385200031PubMedID: 21537050OAI: oai:DiVA.org:uu-258985DiVA: diva2:842935
Available from: 2015-07-23 Created: 2015-07-23 Last updated: 2015-07-23Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Calza, Stefano
By organisation
Department of Immunology, Genetics and Pathology
In the same journal
Journal of Clinical Oncology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 180 hits
ReferencesLink to record
Permanent link

Direct link