ASCO 2017: Association of loss of tumor suppressor ZFP36 with lethal prostate cancer

Chicago, IL (UroToday.com) Inflammation has been linked to prostate cancer (PCa) progression which may be mediated by the transcription factor nuclear factor kappa B (NFκB). Using a bioinformatic screen focused on NFκB pathway activation in lethal PCa, the authors identified the tumor suppressor ZFP36 as a key node of the NFκB network. Furthermore, the authors had shown in vitro that ZFP36 expression was inversely associated with both NFκB-controlled gene levels, and proliferation and sensitivity to enzalutamide.

Therefore, the authors hypothesized that patients who relapse with metastatic disease after radical prostatectomy (RP) will have lower ZFP36 levels in their RP specimens. Additionally, they also hypothesized that ZFP36 levels would be much lower in metastatic disease deposits compared to localized disease. Consequently, in the current study, the authors examined the role of ZFP36 and PCa progression in patient cohorts.

The association between low mRNA expression of ZFP36 (levels in the lower quartile) and lethal PCa (defined as metastatic disease or death) was assessed with logistic regression among men with localized PCa in two independent cohorts treated with RP. The discovery cohort was RP samples from Health Professional Follow-up Study and Physicians Health Study. The validation cohort included RP samples from Cleveland Clinic, Mayo Clinic, Johns Hopkins and Memorial Sloan Kettering Cancer Center. In a third cohort from Cornell University, ZFP36 expression levels were assessed in RP samples from patients with localized PCa and biopsies of metastatic castration-resistant prostate cancer (mCRPC). 

Table 1 shows men with localized PCa and lower quartile of tumor ZFP36 expression had a nearly 2-fold higher risk of lethal PCa after adjusting for known clinical and histological prognostic features (age, RP Gleason score, T-stage). This association was confirmed in the validation cohort. ZFP36 gene expression was also significantly lower in mCRPC (n=53) compared with a localized RP cohort (n=68) (p-value <0.0001).


In conclusion, lower ZFP36 in RP specimens is associated with clinically significant risk of lethal PCa after treatment with curative intent and lower ZFP36 levels are found in metastatic tissue.

Presented By: Christopher Sweeney, MBBS, Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @GoldbergHanan

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA




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