Diagnostic and prognostic value of androgen receptor and AR-V7 expression in bladder cancer

Androgen receptor (AR) pathway has an important role in the growth and development of the male urogenital system. AR pathway also plays a role in the tumorigenesis of several cancers such as prostate and breast cancer. Bladder cancer occurs approximately 3 times more frequently in men than in women, and this male dominance cannot be explained by environmental risk factors. This situation gave rise to the hypothesis that the AR pathway may also have a role in bladder cancer and various studies regarding AR involvement in bladder cancer have been performed. The effect of AR pathway on bladder cancer development has been clearly demonstrated in pre-clinical cell culture and animal experiments, but clinical studies is yet to have a concensus. In all relevant clinical studies, traditional AR (AR-FL) protein was measured by immunohistochemical (IHC) method and conflicting results were obtained. For protein measurement, Western Blot (WB) method is more sensitive than IHC and unlike IHC, WB can provide quantitative data. In addition, no study has evaluated the alterations in AR pathway in bladder cancer at both protein and mRNA levels. AR splice variant – 7 (AR-V7) is the most frequently discussed AR variant and is proven to have a role in prostate cancer. However, the mechanism of AR-FL to AR- V7 transformation has not been clearly understood. There is no study addressing the relationship between AR-V7 bladder cancer up to date. In our study, 23 non-muscle invasive bladder cancer patients' tissues and bladder tissue of 12 healthy individuals were examined. The levels of AR-FL protein, AR-FL mRNA, AR-V7 protein and AR-V7 mRNA were quantitatively measured and compared between the two groups. While AR-FL protein and AR-V7 mRNA were found to be significantly higher in bladder cancer group, AR-FL mRNA and AR-V7 protein were found to be lower (p<0.05). The increase of AR-FL protein, which is known to cause tumorigenesis, in bladder cancer supports the role of AR pathway in bladder cancer. The increase of AR- FL protein, as a result of disruption of the regulatory mechanisms, may have caused suppression of AR-FL mRNA by negative feedback. AR-V7 has been demonstrated for the first time in bladder tissue. Our study reached new and valuable findings in the relationship between bladder cancer and AR pathway. This study will shed light on the studies that aim to clarify the role of the AR pathway in bladder cancer.