A molecular signature predictive of indolent prostate cancer
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 in...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
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American Association for the Advancement of Science
2013
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| _version_ | 1826284448075743232 |
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| author | Irshad, S Bansal, M Castillo-Martin, M Zheng, T Aytes, A Wenske, S Le Magnen, C Guarnieri, P Sumazin, P Benson, M Shen, M Califano, A Abate-Shen, C |
| author_facet | Irshad, S Bansal, M Castillo-Martin, M Zheng, T Aytes, A Wenske, S Le Magnen, C Guarnieri, P Sumazin, P Benson, M Shen, M Califano, A Abate-Shen, C |
| author_sort | Irshad, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T01:13:59Z |
| format | Journal article |
| id | oxford-uuid:8e0352a5-2274-4646-a324-ee38e6d205fb |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:13:59Z |
| publishDate | 2013 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:8e0352a5-2274-4646-a324-ee38e6d205fb2022-03-26T22:54:52ZA molecular signature predictive of indolent prostate cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8e0352a5-2274-4646-a324-ee38e6d205fbSymplectic Elements at OxfordAmerican Association for the Advancement of Science2013Irshad, SBansal, MCastillo-Martin, MZheng, TAytes, AWenske, SLe Magnen, CGuarnieri, PSumazin, PBenson, MShen, MCalifano, AAbate-Shen, CMany 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. |
| spellingShingle | Irshad, S Bansal, M Castillo-Martin, M Zheng, T Aytes, A Wenske, S Le Magnen, C Guarnieri, P Sumazin, P Benson, M Shen, M Califano, A Abate-Shen, C A molecular signature predictive of indolent prostate cancer |
| title | A molecular signature predictive of indolent prostate cancer |
| title_full | A molecular signature predictive of indolent prostate cancer |
| title_fullStr | A molecular signature predictive of indolent prostate cancer |
| title_full_unstemmed | A molecular signature predictive of indolent prostate cancer |
| title_short | A molecular signature predictive of indolent prostate cancer |
| title_sort | molecular signature predictive of indolent prostate cancer |
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