domingo, 22 de septiembre de 2013

A Molecular Signature Predictive of Indolent Prostate Cancer

A Molecular Signature Predictive of Indolent Prostate Cancer

Sci Transl Med
Vol. 5, Issue 202, p. 202ra122
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3006408
  • Research Article
COMPUTATIONAL BIOLOGY

A Molecular Signature Predictive of Indolent Prostate Cancer

  1. Cory Abate-Shen1,2,4,11,
+ Author Affiliations
  1. 1Department of Urology, Columbia University Medical Center, New York, NY 10029, USA.
  2. 2Department of Systems Biology, Columbia University Medical Center, New York, NY 10029, USA.
  3. 3Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  4. 4Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
  5. 5Department of Statistics, Columbia University, New York, NY 10027, USA.
  6. 6Department of Medicine, Columbia University Medical Center, New York, NY 10029, USA.
  7. 7Department of Genetics and Development, Columbia University Medical Center, New York, NY 10029, USA.
  8. 8Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10029, USA.
  9. 9Department of Biomedical Informatics, Columbia University Medical Center, New York, NY 10029, USA.
  10. 10Institute for Cancer Genetics, Columbia University Medical Center, New York, NY 10029, USA.
  11. 11Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10029, USA.
+ Author Notes
  • * These authors contributed equally to this work.
  • Present address: Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  1. Corresponding author. E-mail: califano@c2b2.columbia.edu (A.C.); cabateshen@columbia.edu (C.A.-S.)

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.
Citation: S. Irshad, M. Bansal, M. Castillo-Martin, T. Zheng, A. Aytes, S. Wenske, C. L. Magnen, P. Guarnieri, P. Sumazin, M. C. Benson, M. M. Shen, A. Califano, C. Abate-Shen, A Molecular Signature Predictive of Indolent Prostate Cancer. Sci. Transl. Med. 5, 202ra122 (2013).

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