Correlation Between Androgen Receptor Expression and Prognosis in Prostate Cancer Patients: A Retrospective Study

Metastatic prostate cancer (PC) initially responds to androgen deprivation therapy (ADT) but often progresses to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) expression, partly regulated by promoter-associated CpG methylation, plays a pivotal role in disease progression and therapeutic resistance. In this study, 146 formalin-fixed, paraffin-embedded (FFPE) prostate-related tissue specimens representing five disease states-non-malignant prostate tissue, primary localized PC, hormone-naïve bone metastases, short-term castration metastases, and CRPC bone metastases-were evaluated. Genome-wide promoter methylation was profiled, and AR expression was quantified at transcript and protein levels. Nuclear AR H-score (0-300) was used as the principal protein-level measure. AR H-score differed across clinical states (one-way ANOVA, F = 13.72, p < 0.001). Using the cohort median promoter-methylation beta value (0.51195) as the binary cutpoint, the distribution of low versus high methylation did not differ significantly across the five clinical groups (χ² = 8.42, df = 4, p = 0.077), whereas continuous promoter methylation was inversely correlated with AR H-score (r = -0.480, 95% CI -0.596 to -0.344, p < 0.001). Among the 134 malignant cases included in survival analyses, the AR-high stratum showed longer observed median PFS and OS than the AR-low stratum, while the MCA Kaplan-Meier curves showed substantial overlap. Accordingly, the data support stage-related AR remodeling and an inverse AR-methylation relationship, but do not establish a simple adverse-prognostic effect of high AR expression. The MCA remains exploratory and requires independent validation.