Department of Urology, Medical University of Vienna, Vienna, Austria.
Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
Clin Genitourin Cancer. 2019 Oct;17(5):389-394. doi: 10.1016/j.clgc.2019.06.012. Epub 2019 Jun 26.
The purpose of this study was to investigate the prevalence and prognostic value of the polymorphic variant (1245A>C), a single nucleotide polymorphism (SNP) of the HSD3B1 gene, in the tumors of patients with castration-resistant prostate cancer (CRPC).
We retrospectively evaluated 44 patients with CRPC who underwent palliative transurethral resection of the prostate. Genomic DNA was extracted from formalin-fixed and paraffin-embedded material, and 1245A>C SNP of the HSD3B1 gene was analyzed via Sanger sequencing. Cox regression analysis was used to assess the prognostic value of the respective SNP with time to progression as well as cancer-specific and overall survival in the subgroup of patients receiving second systemic treatment.
The SNP was present in 20 patients (51.2%) who received second line systemic treatment additionally to androgen deprivation, of which 16 (80%) patients were heterozygous and 4 (20%) were homozygous. Correlation analysis revealed no association of the SNP with any clinical characteristics at initiation of second-line systemic treatment. Moreover, the presence of the variant (1245A>C) of HSD3B1 was not associated with any survival endpoint.
The variant allele 1245C of the HSD3B1 gene is present in approximately one-half of patients with CRPC; however, it is not associated with oncologic outcomes. These findings, however, need to be interpreted with caution as the sample size is small. Further research on biomarkers is needed to help tailor clinical decision making in prostate cancer, especially in the increasingly complex therapeutic landscape of CRPC.
本研究旨在探讨雄激素剥夺治疗抵抗性前列腺癌(CRPC)患者肿瘤中 HSD3B1 基因多态性(1245A>C)的流行率及其预后价值。
我们回顾性评估了 44 例接受姑息性经尿道前列腺切除术的 CRPC 患者。从福尔马林固定和石蜡包埋的材料中提取基因组 DNA,并通过 Sanger 测序分析 HSD3B1 基因的 1245A>C SNP。Cox 回归分析用于评估 SNP 与进展时间以及亚组患者接受二线系统治疗后的癌症特异性和总体生存率的相关性。
在另外接受雄激素剥夺治疗的 20 例(51.2%)接受二线系统治疗的患者中存在 SNP,其中 16 例(80%)为杂合子,4 例(20%)为纯合子。相关性分析表明,SNP 与二线系统治疗开始时的任何临床特征均无相关性。此外,HSD3B1 变异(1245A>C)的存在与任何生存终点均无相关性。
HSD3B1 基因的变异等位基因 1245C 约存在于一半的 CRPC 患者中;然而,它与肿瘤学结果无关。然而,由于样本量较小,这些发现需要谨慎解释。需要进一步研究生物标志物,以帮助在前列腺癌中进行临床决策,尤其是在 CRPC 日益复杂的治疗环境中。