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Molecular sampling of prostate cancer: a dilemma for predicting disease progression
Yale University.
Weill Cornell Medical Centre.
Karolinska Institute.
Karolinska Institute.
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2010 (English)In: BMC MEDICAL GENOMICS, ISSN 1755-8794, Vol. 3, no 8Article in journal (Refereed) Published
Abstract [en]

Background: Current prostate cancer prognostic models are based on pre-treatment prostate specific antigen (PSA) levels, biopsy Gleason score, and clinical staging but in practice are inadequate to accurately predict disease progression. Hence, we sought to develop a molecular panel for prostate cancer progression by reasoning that molecular profiles might further improve current clinical models. Methods: We analyzed a Swedish Watchful Waiting cohort with up to 30 years of clinical follow up using a novel method for gene expression profiling. This cDNA-mediated annealing, selection, ligation, and extension (DASL) method enabled the use of formalin-fixed paraffin-embedded transurethral resection of prostate (TURP) samples taken at the time of the initial diagnosis. We determined the expression profiles of 6100 genes for 281 men divided in two extreme groups: men who died of prostate cancer and men who survived more than 10 years without metastases (lethals and indolents, respectively). Several statistical and machine learning models using clinical and molecular features were evaluated for their ability to distinguish lethal from indolent cases. Results: Surprisingly, none of the predictive models using molecular profiles significantly improved over models using clinical variables only. Additional computational analysis confirmed that molecular heterogeneity within both the lethal and indolent classes is widespread in prostate cancer as compared to other types of tumors. Conclusions: The determination of the molecularly dominant tumor nodule may be limited by sampling at time of initial diagnosis, may not be present at time of initial diagnosis, or may occur as the disease progresses making the development of molecular biomarkers for prostate cancer progression challenging.

Place, publisher, year, edition, pages
BioMed Central , 2010. Vol. 3, no 8
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-56306DOI: 10.1186/1755-8794-3-8ISI: 000276848100001OAI: diva2:318298
Original Publication: Andrea Sboner, Francesca Demichelis, Stefano Calza, Yudi Pawitan, Sunita R Setlur, Yujin Hoshida, Sven Perner, Hans-Olov Adami, Katja Fall, Lorelei A Mucci, Philip W Kantoff, Meir Stampfer, Swen-Olof Andersson, Eberhard Varenhorst, Jan-Erik Johansson, Mark B Gerstein, Todd R Golub, Mark A Rubin and Ove Andren, Molecular sampling of prostate cancer: a dilemma for predicting disease progression, 2010, BMC MEDICAL GENOMICS, (3), 8. Copyright: BioMed Central Available from: 2010-05-07 Created: 2010-05-07 Last updated: 2010-05-29

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Varenhorst, Eberhard
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Urology Faculty of Health SciencesDepartment of Urology in Östergötland
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