The level of expression of three genes associated with aging can be used to predict whether seemingly low-risk prostate cancer will remain slow-growing, according to researchers at the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center. Use of this three-gene biomarker, in conjunction with existing cancer-staging tests, could help physicians better determine which men with early prostate cancer can be safely followed with “active surveillance” and spared the risks of prostate removal or other invasive treatment. The findings were published in the online edition of Science Translational Medicine.
In their search for a biomarker for slow-growing prostate cancer, co-senior author Cory Abate-Shen, PhD, and colleagues focused on genes related to aging, particularly those affected by cellular senescence, a phenomenon in which older cells cease to divide but remain metabolically active that has been associated with benign prostate lesions in mouse models and in humans.
Using a technique called gene set enrichment analysis, the team identified 19 genes that are enriched in a mouse model of prostate cancer in which the cancers are invariably indolent. They then used a decision-tree learning model to identify three genes—FGFR1, PMP22, and CDKN1A—that together can accurately predict the outcome of seemingly low-risk tumors. Tumors that test negative for the biomarker are deemed aggressive.
In a blinded retrospective study, the researchers tested the prognostic accuracy of the three-gene panel on initial biopsy specimens from 43 patients who had been monitored for at least 10 years with active surveillance at CUMC. Of the 43, 14 ultimately developed advanced prostate cancer. All 14 were correctly identified by the test. Read the study abstract.