Tristetraprolin Is a Prognostic Biomarker for Poor Outcomes among Patients with Low-Grade Prostate Cancer

Abstract

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). 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 = 1,394) and/or metastatic outcome data (total = 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 the 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. 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 RNA expression provides independent information beyond CAPRA-S to predict BCR. TTP is a promising prostate cancer biomarker for predicting which RP patients will have poor outcomes, especially for low-grade prostate cancer patients. This study suggests that RNA expression can be used to enhance the accuracy of CAPRA-S to predict outcomes in patients treated with RP.

AU-rich element-binding proteins in colorectal cancer

“…The physiological significance of TTP is highlighted by Zfp36 knockout mice, which develop severe inflammatory syndromes and growth retardation[114]. Moreover, TTP expression is frequently lost in human cancers, and this loss is often associated with poor clinical outcomes[115,116].…”

The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

“…Additionally, the low time to reoccurrence in low-TTP tumors was more pronounced in low-grade tumors. This study suggested that TTP is a promising prostate cancer biomarker for predicting the low-grade radical prostatectomy prostate cancer patients that will have poor outcomes [66]. Another study similarly showed low TTP expression in prostate cancer compared to non-cancerous tissues [65].…”

“…Low TTP levels in prostate cancer shorten time to recurrence or metastasis compared with TTP-high tumors [66].…”

“…Induction of TTP inhibited the growth, proliferation, and tumorigenic potential of prostate cancer cells in a mouse xenograft model of prostate cancer [64]. Another study that also investigated prostate cancers, showed that low-TTP tumors had faster reoccurrence or metastasis versus high-TTP tumors [66]. Additionally, the low time to reoccurrence in low-TTP tumors was more pronounced in low-grade tumors.…”

Identification of early stage recurrence endometrial cancer biomarkers using bioinformatics tools

“…Considering the relevance that bioinformatics has gained in translational medicine, several algorithms have been implemented in recent years for the identification of biomarkers with prognostic value in several types of cancer. As an example, gene expression profile analysis performed using genomic and clinical data stored in public repositories has led to the identification of biomarkers with potential prognostic value in prostate ( 36 ) and breast ( 37 ) cancer, among others.…”