Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, U.S.A.
Molecular Pharmacology Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, U.S.A.
Anticancer Res. 2023 Sep;43(9):4023-4030. doi: 10.21873/anticanres.16590.
BACKGROUND/AIM: Gonadotropin-releasing hormone 2 (GNRH2) is a poorly-studied peptide hormone that is widely distributed in the central nervous system and expressed in peripheral tissues of mammals. The non-synonymous rs6051545 variant in GNRH2 (A16V) has been linked to higher serum testosterone concentrations. This study investigated whether the A16V variant is associated with altered androgen-deprivation therapy (ADT) progression-free survival (PFS) and overall survival (OS).
We examined the expression of GNRH2 in prostate tissue microarrays comprising normal tissue, prostatic hyperplasia, and prostate cancer using immunofluorescence. We also evaluated the GNRH2 genotype in 131 patients with prostate cancer who received ADT and compared PFS and OS between the variant and wild-type genotypes.
GNRH2 was detected in all prostate tissues, although expression did not vary with Gleason grade or disease stage (p=0.71). The GNRH2 A16V genotype was not associated with PFS or OS; however, univariate and multivariate analyses revealed Gleason score and definitive local therapy were each associated with PFS (p≤0.0074), whereas age and Gleason score were associated with OS (p≤0.0046).
GNRH2 is expressed in normal, hyperplastic, and neoplastic prostate tissues; the A16V variant is not related to treatment outcome or survival.
背景/目的:促性腺激素释放激素 2(GNRH2)是一种研究较少的肽类激素,广泛分布于中枢神经系统,并在哺乳动物的外周组织中表达。GNRH2 中的非同义 rs6051545 变异(A16V)与较高的血清睾酮浓度有关。本研究旨在探讨 A16V 变异是否与雄激素剥夺治疗(ADT)无进展生存期(PFS)和总生存期(OS)的改变有关。
我们使用免疫荧光法检测了前列腺组织微阵列中正常组织、前列腺增生和前列腺癌组织中 GNRH2 的表达。我们还评估了 131 例接受 ADT 的前列腺癌患者的 GNRH2 基因型,并比较了变异型和野生型基因型之间的 PFS 和 OS。
GNRH2 在所有前列腺组织中均有表达,尽管其表达与 Gleason 分级或疾病分期无关(p=0.71)。GNRH2 A16V 基因型与 PFS 或 OS 无关;然而,单因素和多因素分析显示,Gleason 评分和确定性局部治疗均与 PFS 相关(p≤0.0074),而年龄和 Gleason 评分与 OS 相关(p≤0.0046)。
GNRH2 在正常、增生和肿瘤前列腺组织中表达;A16V 变异与治疗结果或生存无关。