Low tristetraprolin expression is associated with lethal prostate cancer

Abstract

Background: Inflammation is linked to prostate cancer enzalutamide sensitivity. Men with localized prostate cancer progression and is mediated by NF-kB. Tristetraprolin is a key and lower quartile of tumor tristetraprolin expression had a node of NF-kB activation and we investigated its biological significant, nearly two-fold higher risk of lethal prostate cancer and prognostic role in lethal prostate cancer. after adjusting for known clinical and histologic prognostic Methods: In vitro assays assessed the function of tristetrapro-features (age, RP Gleason score, T-stage). Tristetraprolin lin and the association between low mRNA tristetraprolin levels expression was also significantly lower in mCRPC compared and lethal prostate cancer (metastatic disease or death) was with localized prostate cancer. assessed across independent prostatectomy cohorts: (i) nested Conclusions: Lower levels of tristetraprolin in human pros-case-control studies from Health Professionals Follow-up Study tate cancer prostatectomy tissue are associated with more and Physicians' Health Study, and (ii) prostatectomy samples aggressive prostate cancer and may serve as an actionable from Cleveland Clinic, Mayo Clinic, Johns Hopkins and Memo-prognostic and predictive biomarker. rial Sloan Kettering Cancer Center. Tristetraprolin expression Impact: There is a clear need for improved biomarkers to levels in prostatectomy samples from patients with localized identify patients with localized prostate cancer in need of disease and biopsies of metastatic castration–resistant prostate treatment intensification, such as adjuvant testosterone sup-cancer (mCRPC) were assessed in a Cornell University cohort. pression, or treatment de-intensification, such as active sur-Results: In vitro tristetraprolin expression was inversely veillance. Tristetraprolin levels may serve as informative bio-associated with NF-kB–controlled genes, proliferation, and markers in localized prostate cancer.