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Nur77 可作为与免疫浸润相关的潜在预后生物标志物,并且可能作为前列腺腺癌的一个良好治疗靶点。

Nur77 Serves as a Potential Prognostic Biomarker That Correlates with Immune Infiltration and May Act as a Good Target for Prostate adenocarcinoma.

机构信息

Taizhou Central Hospital (Taizhou University Hospital), School of Medicine, Taizhou University, Taizhou 318000, China.

Department of Pharmacy, Hebei Key Laboratory of Neuropharmacology, Hebei North University, Zhangjiakou 075000, China.

出版信息

Molecules. 2023 Jan 28;28(3):1238. doi: 10.3390/molecules28031238.

Abstract

Prostate adenocarcinoma (PRAD) is the most frequent malignancy, and is the second leading cause of death due to cancer in men. Thus, new prognostic biomarkers and drug targets for PRAD are urgently needed. As we know, nuclear receptor Nur77 is important in cancer development and changes in the tumor microenvironment; whereas, the function of Nur77 in PRAD remains to be elucidated. The TCGA database was used to explore the Nur77 expression and its role in the prognosis of PRAD. It was shown that Nur77 was down regulated in PRAD, and low Nur77 expression was correlated with advanced clinical pathologic characteristics (high grade, histological type, age) and poor prognosis. Furthermore, key genes screening was examined by univariate Cox analysis and Kaplan-Meier survival. Additionally, Nur77 was closely related to immune infiltration and some anti-tumor immune functions. The differentially expressed genes (DEGs) were presented by protein-protein interaction (PPI) network analysis. Therefore, the expression level of Nur77 might help predict the survival of PRAD cases, which presents a new insight and a new target for the treatment of PRAD. In vitro experiments verified that natural product malayoside targeting Nur77 exhibited significant therapeutic effects on PRAD and largely induced cell apoptosis by up-regulating the expression of Nur77 and its mitochondrial localization. Taken together, Nur77 is a prognostic biomarker for patients with PRAD, which may refresh the profound understanding of PRAD individualized treatment.

摘要

前列腺腺癌 (PRAD) 是最常见的恶性肿瘤,也是男性癌症死亡的第二大主要原因。因此,迫切需要新的前列腺腺癌预后生物标志物和药物靶点。众所周知,核受体 Nur77 在癌症发展和肿瘤微环境变化中起着重要作用;然而,Nur77 在 PRAD 中的功能仍有待阐明。本研究使用 TCGA 数据库探讨 Nur77 的表达及其在 PRAD 预后中的作用。结果表明,Nur77 在 PRAD 中下调,低表达 Nur77 与高级临床病理特征(高分级、组织学类型、年龄)和不良预后相关。此外,通过单变量 Cox 分析和 Kaplan-Meier 生存分析对关键基因进行了筛选。此外,Nur77 与免疫浸润和一些抗肿瘤免疫功能密切相关。通过蛋白质-蛋白质相互作用 (PPI) 网络分析呈现差异表达基因 (DEGs)。因此,Nur77 的表达水平可能有助于预测 PRAD 病例的生存情况,为 PRAD 的治疗提供了新的见解和新的靶点。体外实验验证,靶向 Nur77 的天然产物马槟榔苷对 PRAD 具有显著的治疗作用,通过上调 Nur77 的表达及其线粒体定位,大量诱导细胞凋亡。总之,Nur77 是 PRAD 患者的预后生物标志物,可能会刷新对 PRAD 个体化治疗的深刻理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1269/9921667/4e49b7eac973/molecules-28-01238-g001.jpg

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