거세 저항 전립선암 환자에서 당질코르티코이드 수용체 mRNA 발현과 안드로젠 수용체 표적치료의 효과

Abstract

Objectives: To investigate the association of glucocorticoid receptor (GR) expression in castration-resistant prostate cancer (CRPC) tissue samples with treatment response to androgen receptor (AR)-targeting therapy

Materials and methods: mRNA levels of GR, full-length AR (AR-FL) and AR splice variants (AR-V7) were measured in prostate cancer tissue from 52 prospectively enrolled CRPC patients. Thirty-eight patients were starting AR-targeting therapy, and 14 patients were starting taxane-based chemotherapy. The primary endpoint was prostate-specific antigen (PSA) response rate to treatment. Secondary endpoints were PSA progression-free survival, radiologic progression-free survival, and overall survival. Patients were divided into groups based on high versus low AR-V7/AR-FL ratios, and high versus low GR/AR-FL ratios.

Results: AR-V7 mRNA was detected in 45 patients (86.5%), and GR mRNA was detected in 51 patients (98.1%). In patients with AR-targeting therapy, PSA response rate was higher in patients with low AR-V7/AR-FL ratios (77.8% vs. 25.0%, p=0.003) and low GR/AR-FL ratios (81.3% vs. 27.3%, p=0.003). Among patients receiving AR-targeting therapy, patients with low GR/AR-FL ratios had better 1-year rates of PSA progression-free survival (80.8% vs. 17.3%, p=0.003) and radiologic progression-free survival (75.7% vs. 24.4%, p=0.005). However, the 1-year overall survival rate was similar between the two groups (93.8% vs. 84.8%, p=0.246). The high GR/AR-FL ratio was associated with low PSA response to AR-targeting therapy in multivariable models (HR 0.142; 95% CI 0.021-0.778; p=0.030).

Conclusion: Increased GR expression as well as increased AR-V7 expression relative to full-length AR may be associated with reduced treatment response to AR-targeting therapies. Although GR expression was not associated with overall survival, GR may play a role as a biomarker in patient with CRPC.