A Molecular Signature Predictive of Indolent Prostate Cancer

Sci Transl Med 11 September 2013:
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. Shazia Irshad¹,*,†,
2. Mukesh Bansal²,*,
3. Mireia Castillo-Martin³,
4. Tian Zheng⁴,⁵,
5. Alvaro Aytes¹,
6. Sven Wenske¹,⁴,
7. Clémentine Le Magnen¹,
8. Paolo Guarnieri²,⁴,
9. Pavel Sumazin²,
10. Mitchell C. Benson¹,⁴,
11. Michael M. Shen²,⁴,⁶,⁷,
12. Andrea Califano²,⁴,⁸,⁹,¹⁰,‡ and
13. 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.

• Copyright © 2013, American Association for the Advancement of Science

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).

Read the Full Text

The editors suggest the following Related Resources on Science sites Back to Top

In

• Research Article: Epilepsy Optogenetic and Potassium Channel Gene Therapy in a Rodent Model of Focal Neocortical Epilepsy

  • Robert C. Wykes,
  • Joost H. Heeroma,
  • Laura Mantoan,
  • Kaiyu Zheng,
  • Douglas C. MacDonald,
  • Karl Deisseroth,
  • Kevan S. Hashemi,
  • Matthew C. Walker,
  • Stephanie Schorge,
  • and Dimitri M. Kullmann

  Sci Transl Med 21 November 2012 4:161ra152. Published ahead of print 12 November 2012,
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)
  • Supplementary Materials

In Science Translational Medicine

• Research Article: Cancer Extended Survival of Glioblastoma Patients After Chemoprotective HSC Gene Therapy

  • Jennifer E. Adair,
  • Brian C. Beard,
  • Grant D. Trobridge,
  • Tobias Neff,
  • Jason K. Rockhill,
  • Daniel L. Silbergeld,
  • Maciej M. Mrugala,
  • and Hans-Peter Kiem

  Sci Transl Med 9 May 2012 4:133ra57
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)
  • Supplementary Materials
• Research Article: Gene Therapy AAV2 Gene Therapy Readministration in Three Adults with Congenital Blindness

  • Jean Bennett,
  • Manzar Ashtari,
  • Jennifer Wellman,
  • Kathleen A. Marshall,
  • Laura L. Cyckowski,
  • Daniel C. Chung,
  • Sarah McCague,
  • Eric A. Pierce,
  • Yifeng Chen,
  • Jeannette L. Bennicelli,
  • Xiaosong Zhu,
  • Gui-shuang Ying,
  • Junwei Sun,
  • J. Fraser Wright,
  • Alberto Auricchio,
  • Francesca Simonelli,
  • Kenneth S. Shindler,
  • Federico Mingozzi,
  • Katherine A. High,
  • and Albert M. Maguire

  Sci Transl Med 8 February 2012 4:120ra15
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)
  • Supplementary Materials
• Research Article: Gene Therapy Dosage Thresholds for AAV2 and AAV8 Photoreceptor Gene Therapy in Monkey

  • Luk H. Vandenberghe,
  • Peter Bell,
  • Albert M. Maguire,
  • Cassia N. Cearley,
  • Ru Xiao,
  • Roberto Calcedo,
  • Lili Wang,
  • Michael J. Castle,
  • Alexandra C. Maguire,
  • Rebecca Grant,
  • John H. Wolfe,
  • James M. Wilson,
  • and Jean Bennett

  Sci Transl Med 22 June 2011 3:88ra54
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)
  • Supplementary Materials
• Perspective: HIV/AIDS Gene Therapy Takes a Cue from HAART: Combinatorial Antiviral Therapeutics Reach the Clinic

  • Priya S. Shah and
  • David V. Schaffer

  Sci Transl Med 16 June 2010 2:36ps30
  • Abstract
  • Full Text
  • Full Text (PDF)
• Research Article: Retinal Disease Safety and Efficacy of Subretinal Readministration of a Viral Vector in Large Animals to Treat Congenital Blindness

  • Defne Amado,
  • Federico Mingozzi,
  • Daniel Hui,
  • Jeannette L. Bennicelli,
  • Zhangyong Wei,
  • Yifeng Chen,
  • Erin Bote,
  • Rebecca L. Grant,
  • Jeffrey A. Golden,
  • Kristina Narfstrom,
  • Nasreen A. Syed,
  • Stephen E. Orlin,
  • Katherine A. High,
  • Albert M. Maguire,
  • and Jean Bennett

  Sci Transl Med 3 March 2010 2:21ra16
  • Editor's Summary
  • Abstract
  • Full Text
  • Full Text (PDF)
  • Supplementary Material