Biomarkers Show Promise Improving Prostate Cancer Care

The identification of biomarkers that can predict for future disease states is critical to our ability to decrease patient morbidity and mortality associated with prostate cancer.

Scientists at the Fred Hutchinson Cancer Research Center (Seattle, WA, USA) working with their colleagues in various University of California campuses utilized prostate tissue samples that were taken from a series of 332 men who underwent radical prostatectomy between 1991 and 2003. The median age of diagnosis was 63 with a mean preprostatectomy prostate-specific antigen PSA of 10.2 ng/mL.

The team determined the frequency of genomic mutations or amplification of two proteins the Y-box binding protein (YB-1) and the Metastasis-associated protein (MTA1). The tissue microarray (TMA) was constructed using a Manual Tissue Arrayer (MTA; Beecher Instruments Inc., Sun Prairie, WI, USA). At least three cores of each histology type were taken from the surgical blocks and placed into the TMA block. The final TMA was sectioned into 4-micron slices and stained. Immunofluorescence staining was performed and protein expression was performed utilizing the BZ-9000 BIOREVO fluorescence microscope (Keyence, Itasca, IL, USA) at 20× magnification.

The investigators found that patients with higher levels of the two proteins, YB-1 and MTA1, were much more likely to suffer prostate cancer recurrence and three times as likely to require treatment such as hormone therapy or radiation therapy. Moreover, adding YB-1 and MTA1 levels to clinical factors currently used to predict prostate cancer recurrence improved their predictive potential.

Andrew C. Hsieh, MD, one the senior co-authors of the study, said, “Proteins are cells' work horses. They underpin how cells live, behave and die. But the process of producing proteins from RNA messenger molecules is not static. It's not like a factory that does the same thing every time. There are levels of regulation and changes in how key proteins are produced, independent of alterations to the proteins' genes or messenger RNA, have been shown to drive cancer.” YB-1 and MTA1 are just two of potentially hundreds of such proteins, and would never have been discovered if Dr. Hsieh had not ventured beyond traditional DNA and RNA biomarker discovery techniques. The study was published on March 3, 2015, in the journal Oncotarget.

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