Research ArticleComputational Biology

A Molecular Signature Predictive of Indolent Prostate Cancer

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Science Translational Medicine  11 Sep 2013:
Vol. 5, Issue 202, pp. 202ra122
DOI: 10.1126/scitranslmed.3006408

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To Treat or Not to Treat...*

...That is often the question for prostate cancer patients and their caretakers. Now, Irshad et al. describe a gene signature that may guide treatment choices when prognosis is unclear.

Along with other clinical and molecular parameters, pathologists use the Gleason grading system to stage prostate cancers and predict patient prognosis. A Gleason score is assigned to a cancer on the basis of its microscopic features and is directly related to tumor aggressiveness and poor prognosis. Most newly diagnosed prostate cancers with low Gleason scores require no treatment intervention and are monitored with active surveillance (indolent tumors). However, the pinpointing of tumors that are aggressive and lethal despite having low Gleason scores is a clinical challenge. In these cases, new tools are needed to answer the title question.

Irshad and colleagues show that low Gleason score prostate tumors can be separated into distinct indolent and aggressive subgroups on the basis of their expression of aging and senescence genes. Using patient tissue samples and gene expression data along with computational biology techniques, including a decision tree learning model, the authors identified three genes—FGFR1, PMP22, and CDKN1A—that predicted the clinical outcome of low Gleason score prostate tumors. The prognostic power of the three-gene signature was validated in independent patient cohorts, and expression of the FGFR1, PMP22, and CDKN1A proteins in biopsy samples identified Gleason 6 patients who had failed surveillance over a 10-year period.

Just as Hamlet laments in his famous soliloquy, oncologists and patients need more information about the unknown before making a decision. The new signature might aid in the choice between “bear[ing] those ills [they] have” with active surveillance or actively treating—and hopefully thwarting—aggressive tumors.

*Paraphrased from the “To be, or not to be” soliloquy in Hamlet by William Shakespeare.

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