BERKELEY, CA (UroToday.com) - When a man is diagnosed with prostate cancer, he and his physician(s) must decide on the best course of treatment. Because not all prostate cancer will progress to aggressive disease and any treatment comes with considerable side-effects, biomarkers that can predict the likelihood of recurrence are desperately needed to aid men and their physicians in making appropriate therapeutic decisions. In a recently published paper in Cancer Research (1), Long et al. have identified and validated biomarkers that can help to predict the likelihood of prostate cancer recurrence after surgery. This new set of biomarkers predicts biochemical recurrence (BCR) and is composed of a 24-gene panel that was identified following RNA sequencing of 97 formalin-fixed paraffin-embedded (FFPE) radical prostatectomy samples from three independent hospitals.[1] This panel showed significant improvement of prediction of BCR over clinical parameters alone and over previously described biomarker panels (from Myriad Genetics) based on cellular proliferation. Furthermore, our group at Emory University validated this panel of 24 biomarkers on an independent public dataset[2] and found that they were significant (p < 8 E-5) at predicting BCR-free survival for 140 cases.
This study is significant and innovative because performing RNAseq on fragmented RNA from FFPE samples is highly challenging, and FFPE specimens with long-term follow-up clinical data represent a vast and largely underutilized resource that is much more abundant than frozen tissues. Because these biomarkers were identified directly from FFPE tissues, it may be more reliable to translate them into a useful clinical test for FFPE specimens. Nevertheless, additional validation using alternative platforms will be necessary both to simplify the assay and to provide independent validation across technology platforms and patient cohorts.
A more clinically relevant point of utility for these biomarkers would be at the point of positive biopsy before treatment. The next step in the process of translating this research to patients is to develop a clinical test that will be easy to use and provide clear results. Ideally, these biomarkers would be used at the time prostate cancer is initially diagnosed through the use of biopsies. Dr. Moreno’s team at Emory University also plans to test whether these biomarkers are useful at discriminating indolent from aggressive disease, but additional work is needed to test whether this will be the case.
References:
- Long Q, Xu J, Osunkoya AO, Sannigrahi S, Johnson BA, Zhou W, Gillespie T, Park JY, Nam RK, Sugar L, Stanimirovic A, Seth AK, Petros JA, and Moreno CS: Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence. Cancer Res 74: 3228-3237, 2014.
- Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, Arora VK, Kaushik P, Cerami E, Reva B, Antipin Y, Mitsiades N, Landers T, Dolgalev I, Major JE, Wilson M, Socci ND, Lash AE, Heguy A, Eastham JA, Scher HI, Reuter VE, Scardino PT, Sander C, Sawyers CL, and Gerald WL: Integrative genomic profiling of human prostate cancer. Cancer Cell 18: 11-22, 2010.
Written by:
Carlos S. Moreno, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Amy and Nevin Kreisler Scholar
Associate Professor
Department of Pathology & Laboratory Medicine
Department of Biomedical Informatics
Emory University School of Medicine
Atlanta, GA 30322 USA
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