Abstract

Background: We studied the utility of the tumor suppressor Tristetraprolin (TTP, ZFP36) as a clinically relevant biomarker of aggressive disease in prostate cancer patients after radical prostatectomy (RP).

Methods: TTP RNA expression was measured in an RP cohort of patients treated at Moffitt Cancer Center (MCC) and obtained from six publically available RP datasets with biochemical recurrence (BCR) (total n=1,394) and/or metastatic outcome data (total n=1,222). TTP protein expression was measured by immunohistochemistry in a tissue microarray of 153 MCC RP samples. The time to BCR or metastasis based on TTP RNA or protein levels was calculated using Kaplan-Meier analysis. Univariable and multivariable Cox proportional hazard models were performed on multiple cohorts to evaluate if TTP is a clinically relevant biomarker, and to assess if TTP improves upon the Cancer of the Prostate Risk Assessment postsurgical (CAPRA-S) score for predicting clinical outcomes.

Results: In all of the RP patient cohorts, prostate cancer with low TTP RNA or protein levels had decreased time to BCR or metastasis versus TTP-High tumors. Further, the decreased time to BCR in TTP-Low prostate cancer was more pronounced in low-grade tumors. Finally, pooled survival analysis suggests that TTP RNA expression provides independent information beyond CAPRA-S to predict BCR.

Conclusions: TTP is a promising prostate cancer biomarker for predicting which RP patients will have poor outcomes, especially for low-grade prostate cancer patients.

Impact: This study suggests that TTP RNA expression can be used to enhance the accuracy of CAPRA-S to predict outcomes in patients treated with RP.

Citation

Rounbehler RJ, Berglund AE, Gerke TA, Takhar MM, Awasthi S, Li W, Davicioni E, Erho NG, Ross AE, Schaeffer EM, Klein EA, Karnes RJ, Jenkins RB, Cleveland JL, Park JY, Yamoah K. Tristetraprolin is a prognostic biomarker for poor outcomes among patients with low-grade prostate cancer. Cancer Epidemiol Biomarkers Prev 2018; In press.