风险因素与前列腺癌有关，包括年龄、环境、种族和民族。Cyclic-adenosine-monophosphate-response-element-binding protein 3调节因子（CREBRF）基因的遗传变异在太平洋岛民中频繁观察到，并且该人群患前列腺癌的发病率较高。CREBRF已被证明在其他癌症中起着作用，然而它在前列腺稳态和肿瘤发生中的功能尚未被先前研究。我们通过公开数据库确定了CREBRF变异的发生率，并检验了CREBRF基因缺失对小鼠前列腺的影响，以确定CREBRF是否影响前列腺生理或病理。通过cBioPortal的多个公开数据集的电算分析，确定了前列腺癌患者中的CREBRF变异。制备雄性Crebrf敲除和野生型小鼠，并在四个月时检测前列腺缺陷。免疫组化染色肝紫质组织切片用于确定CREBRF缺失对前列腺增殖、凋亡、炎症和血管密度的影响。使用Luminex Multiplex Assay测量血清脂联素水平。CREBRF变异在多达4.05％的前列腺肿瘤中被发现，且发现的突变被归类为可能有害的。患有CREBRF基因变异的前列腺癌患者的中位生存期为41.23个月，而没有这些变化的患者则为131个月。在小鼠模型中，Crebrf敲除小鼠的前列腺具有减少的上皮细胞增殖和增加的TUNEL+细胞凋亡。血液循环的脂联素PAI-1和MCP-1也与年龄相匹配的对照组Crebrf敲除小鼠相比发生了改变。患有CREBRF基因变异的前列腺癌患者的整体生存期明显下降，这表明野生型的CREBRF可能在限制前列腺肿瘤发生和进展方面发挥作用。小鼠敲除模型证明了CREBRF可以调节前列腺增殖、凋亡和巨噬细胞密度。血清脂联素PAI-1和MCP-1的水平也发生了改变，并可能对Crebrf敲除小鼠的前列腺观察到的表型变化作出贡献。未来的研究应聚焦于易感性CREBRF突变的人群和机制研究，以完全阐明CREBRF在前列腺肿瘤发生中的潜在作用。AJCEU版权所有 © 2023。

Risk factors for prostate cancer include age, environment, race and ethnicity. Genetic variants in cyclic-adenosine-monophosphate-response-element-binding protein 3 regulatory factor (CREBRF) gene are frequently observed in Pacific Islanders, a population with elevated prostate cancer incidence. CREBRF has been shown to play a role in other cancers, however its function in prostate homeostasis and tumorigenesis has not been previously explored. We determined the incidence of CREBRF alterations in publicly available databases and examined the impact of CREBRF deletion on the murine prostate in order to determine whether CREBRF impacts prostate physiology or pathophysiology.Alterations in CREBRF were identified in prostate cancer patients via in silico analysis of several publicly available datasets through cBioPortal. Male Crebrf knockout and wild-type littermate mice were generated and examined for prostate defects at 4 months of age. Immunohistochemical staining of murine prostate sections was used to determine the impact of Crebrf knockout on proliferation, apoptosis, inflammation and blood vessel density in the prostate. Serum adipokine levels were measured using a Luminex Multiplex Assay.CREBRF alterations were identified in up to 4.05% of prostate tumors and the mutations identified were categorized as likely damaging. Median survival of prostate cancer patients with genetic alterations in CREBRF was 41.23 months, compared to 131 months for patients without these changes. In the murine model, the prostates of Crebrf knockout mice had reduced epithelial proliferation and increased TUNEL+ apoptotic cells. Circulating adipokines PAI-1 and MCP-1 were also altered in Crebrf knockout mice compared to age-matched controls.Prostate cancer patients with genetic alterations in CREBRF had a significantly decreased overall survival suggesting that wild type CREBRF may play a role in limiting prostate tumorigenesis and progression. The murine knockout model demonstrated that CREBRF could modulate proliferation and apoptosis and macrophage density in the prostate. Serum levels of adipokines PAI-1 and MCP-1 were also altered and may contribute to the phenotypic changes observed in the prostates of Crebrf knockout mice. Future studies focused on populations susceptible to CREBRF mutations and mechanistic studies will be required to fully elucidate the potential role of CREBRF in prostate tumorigenesis.AJCEU Copyright © 2023.