Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Department of Urology, Graduate School of Medicine, Akita University, Akita, 010-8543, Japan.
Pharmacogenomics J. 2021 Feb;21(1):102-105. doi: 10.1038/s41397-020-00188-3. Epub 2020 Sep 22.
Genetic polymorphism in YB-1 was previously shown to be associated with the prognosis of advanced prostate cancer patients treated with primary androgen-deprivation therapy. However, the significance of this polymorphism remains invalidated. In this study, we aimed to validate the prognostic significance of the YB-1 genetic polymorphism in metastatic prostate cancer. This study included 79 Japanese patients who were diagnosed as metastatic prostate cancer between 2000 and 2016. Genomic DNA was obtained from patient whole blood samples, and genotyping on YB-1 (rs12030724) was performed by PCR-based technique. The association of genotype in YB-1 with clinicopathological parameters and oncological outcome, including progression-free survival and overall survival, was examined. Homozygous wild-type (AA), heterozygous variant (AT), and homozygous variant (TT) were identified in 47 (59.5%), 26 (32.9%) and 6 patients (7.6%), respectively. Heterozygous/homozygous variant (AT/TT) in YB-1 was significantly associated with lower progression risk compared with homozygous wild-type (AA) (hazard ratio = 0.52; 95% confidence interval = 0.30-0.88, P = 0.015). Consistent with this finding, heterozygous/homozygous variant (AT/TT) in YB-1 was significantly associated with lower risk of any-cause mortality compared with homozygous wild-type (AA) (hazard ratio = 0.46; 95% confidence interval = 0.21-0.93, P = 0.031). Gene polymorphism in YB-1 rs12030724 was validated to be a promising predictive biomarker of androgen-deprivation therapy in metastatic prostate cancer to identify patients requiring more intensive therapeutics.
YB-1 基因多态性先前被证实与接受雄激素剥夺治疗的晚期前列腺癌患者的预后相关。然而，这种多态性的意义仍然未得到验证。在这项研究中，我们旨在验证 YB-1 基因多态性在转移性前列腺癌中的预后意义。这项研究纳入了 79 名在 2000 年至 2016 年间被诊断为转移性前列腺癌的日本患者。从患者全血样本中提取基因组 DNA，并通过基于 PCR 的技术对 YB-1（rs12030724）进行基因分型。检测 YB-1 基因型与临床病理参数和肿瘤学结局（包括无进展生存期和总生存期）之间的关系。野生型（AA）、杂合变异型（AT）和纯合变异型（TT）在 47 例（59.5%）、26 例（32.9%）和 6 例（7.6%）患者中分别被鉴定出来。与纯合野生型（AA）相比，杂合/纯合变异型（AT/TT）在 YB-1 中与较低的进展风险显著相关（风险比=0.52；95%置信区间=0.30-0.88，P=0.015）。与这一发现一致的是，杂合/纯合变异型（AT/TT）在 YB-1 中与纯合野生型（AA）相比，与任何原因死亡率的风险降低显著相关（风险比=0.46；95%置信区间=0.21-0.93，P=0.031）。YB-1 rs12030724 的基因多态性被验证为雄激素剥夺治疗转移性前列腺癌的有前途的预测生物标志物，可识别需要更强化治疗的患者。
