Androgen Receptor Pathway Gene Expression After High Dose Rate Prostate Brachytherapy

Abstract

<h3>Purpose/Objective(s)</h3> Androgen deprivation therapy (ADT) is commonly used after radiation therapy in the treatment of prostate cancer. Though radiation has generally been shown to upregulate androgen receptor (AR) expression, the effect of high dose rate (HDR) brachytherapy on AR expression is unknown. We hypothesize that expression of AR and corresponding target genes will be altered by HDR brachytherapy. <h3>Materials/Methods</h3> 10 Patients with intermediate risk prostate cancer (age 51-78; 7 GS 3+4, 3 GS 4+3) underwent HDR brachytherapy (2 implants, 13.5 Gy per implant, 1 week apart). Patients consented to biopsies before each fraction at the first and second implant. Tumor content percentage was evaluated on stained H&E slides. Bulk RNA-seq gene expression was performed on the formalin-fixed, paraffin-embedded pre- vs. post-RT tumor samples, and differential gene expression was performed to assess changes in AR, KLK2, KLK3, TMPRSS2. <h3>Results</h3> AR pathway genes showed significant downregulation (log2 fold change, adjusted <i>P</i>-value): AR (-0.83, 2.38E-4), KLK2 (-1.65, 2.09E-5), KLK3 (-1.76, 9.7E-4), TMPRSS2 (-1.98, 4.13E-7). Therefore, AR pathway gene expression was 25-56% of baseline expression 1 week after radiation treatment with 13.5 Gy. Meanwhile, post-radiation tumor content (mean fold change +/- standard deviation) was observed to remain 73% +/- 25% of baseline content. <h3>Conclusion</h3> Differential gene expression analysis of prostate tumor suggests AR and its target genes may be downregulated relative to tumor content after HDR brachytherapy.