Prostate cancer is a leading cause of cancer-related death in American men, second only to lung cancer. While clinically localized prostate cancer can be effectively ablated using surgical or radiation treatments, advanced disease, however, remains essentially incurable. It is therefore essential to distinguish aggressive versus indolent forms of prostate cancer at an earlier stage in order to select patients at high risk of cancer recurrence for additional treatments and to spare others from unnecessary treatments. Pretreatment nomorams have been developed to predict prostate cancer recurrence after treatment for localized prostate cancer. Recently molecular biomarkers have been shown to greatly improve the performance of the existing nomograms, suggesting that molecular markers are helpful in increasing the ability to predict patient outcome.
Researchers at the University of Michigan have identified a gene ADRB2, whose mRNA is down-regulated in a number of cancers including prostate cancer, breast cancer and lung cancer. The ADRB2 transcript was strongly repressed in the metastatic tumors compared with benign prostate tissues and clinically localized prostate cancer. The researchers also found that the low ADRB2 protein level was significantly associated with clinical failure (e.g. recurrence of disease after prostatectomy). Therefore, ADRB2 can be used as a prognostic biomarker for aggressive prostate cancer.
ADRB2 (Adrenergic Receptor, Beta 2), is a critical mediator of beta-adrenergic signaling. EZH2-containing PcG Repressive Complex 2 (PRC2) is recruited to the ADRB2 promoter and represses ADRB2 expression by trimethylating histone H3K27. We have previously demonstrated that ADRB2 expression is considerably down-regulated in metastatic prostate cancer. We also found that low ADRB2 expression in a cohort of clinically localized prostate cancer is significantly associated with PSA recurrence (Reference: Yu et al., PMID:17996646). These findings support the potential of ADRB2 to predict clinical outcome and help to select patients at high-risk for aggressive forms of prostate cancer.
In an independent cohort of 328 patients with clinically localized prostate cancer patients, ADRB2 cyto index (which is a measure of cytoplasmic expression of ADRB2) was employed to determine ADRB2 association with prostate cancer outcome and other clinico-pathological parameters in prostate cancer. In this cohort, a loss of ADRB2 was associated with poor outcome. However, cases with either very high or very low expression of adrb2 were associated with good outcome compared to the cases which had intermediate expression of ADRB2 in this cohort. This could be partly related to the fact that the majority of the prostate cancer cases fall into the intermediate expression category in this cohort.
- Predicting clinical outcomes of localized prostate cancer
- A novel biomarker for aggressive prostate cancer.
- A new therapeutic target for prostate cancer treatments.
- ADRB2 is a strong predictor of clinical outcome of prostate cancer treatment better than the following prediction parameters: age, Gleason score, maximum tumor dimension, surgical margin status, and pre-operative PSA.
- ADRB2 protein level will be an additional variable to help patients and their physicians evaluate the aggressiveness of prostate cancer and to choose appropriate treatments.