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NDRG1/2作为宫颈癌的预后预测生物标志物及其与免疫浸润的相关性。

NDRG1/2 as a prognostic predictive biomarker of cervical cancer and its correlation with immune infiltration.

作者信息

Zhang Yuan, Li Bingjie, Li Jie, Zhao Jing, Li Yan, Kang Shan

机构信息

Department of Obstetrics and Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Obstetrics and Gynecology, Hebei General Hospital, Shijiazhuang, China.

出版信息

Biomark Med. 2025 May;19(9):329-339. doi: 10.1080/17520363.2025.2483495. Epub 2025 Apr 7.

DOI:10.1080/17520363.2025.2483495
PMID:40190258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12051547/
Abstract

BACKGROUND

Cervical cancer (CC) is a leading cause of cancer-related death in women. The N-myc down-stream regulatory gene (NDRG) family has an unclear prognostic role in CC.

METHODS

We analyzed NDRG mRNA and protein levels in CC using public databases. And NDRG1 expression was verified through immunohistochemistry in clinical samples. Additionally, we utilized other bioinformatics tools to analyze the correlations between NDRG and survival, as well as immune infiltration.

RESULTS

NDRG1 was elevated, and NDRG2 was reduced in CC tissues. High NDRG1 and low NDRG2/3 correlated with poorer survival and were associated with reduced immune cell infiltration, particularly CD8+ T cells. Genetic alterations in NDRG1/2/3 were primarily amplifications, while DNA hypomethylation of NDRG1 in CC tissues, particularly at specific CpG sites, was associated with prognosis. PPI and enrichment analyses implicated NDRGs in metabolic processes, HIF-1 signaling, and immune regulation, underscoring their roles in CC progression and prognosis.

CONCLUSIONS

NDRG1/2 present potential as new prognostic biomarkers, shedding light on therapeutic targets for CC.

摘要

背景

宫颈癌(CC)是女性癌症相关死亡的主要原因。N-myc下游调控基因(NDRG)家族在CC中的预后作用尚不清楚。

方法

我们使用公共数据库分析了CC中NDRG的mRNA和蛋白质水平。并通过免疫组织化学在临床样本中验证了NDRG1的表达。此外,我们利用其他生物信息学工具分析了NDRG与生存以及免疫浸润之间的相关性。

结果

CC组织中NDRG1升高,NDRG2降低。高NDRG1和低NDRG2/3与较差的生存相关,并与免疫细胞浸润减少有关,尤其是CD8+T细胞。NDRG1/2/3的基因改变主要是扩增,而CC组织中NDRG1的DNA低甲基化,特别是在特定的CpG位点,与预后相关。蛋白质-蛋白质相互作用(PPI)和富集分析表明NDRG参与代谢过程、缺氧诱导因子-1(HIF-1)信号传导和免疫调节,突出了它们在CC进展和预后中的作用。

结论

NDRG1/2具有作为新的预后生物标志物的潜力,为CC的治疗靶点提供了线索。

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本文引用的文献

1
NDRG1 in Aggressive Breast Cancer Progression and Brain Metastasis.NDRG1 在侵袭性乳腺癌进展和脑转移中的作用。
J Natl Cancer Inst. 2022 Apr 11;114(4):579-591. doi: 10.1093/jnci/djab222.
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Web-Based Survival Analysis Tool Tailored for Medical Research (KMplot): Development and Implementation.专为医学研究量身定制的基于网络的生存分析工具(KMplot):开发与应用
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NDRG1 regulates Filopodia-induced Colorectal Cancer invasiveness via modulating CDC42 activity.NDRG1 通过调节 CDC42 的活性来调控片状伪足诱导的结直肠癌侵袭性。
Int J Biol Sci. 2021 Apr 17;17(7):1716-1730. doi: 10.7150/ijbs.56694. eCollection 2021.
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High expression of NDRG3 correlates with poor prognosis in gastric cancer patients.NDRG3 高表达与胃癌患者预后不良相关。
Rev Esp Enferm Dig. 2021 Jul;113(7):524-528. doi: 10.17235/reed.2021.7723/2020.
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Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020:全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
6
Hypermethylation-mediated silencing of NDRG4 promotes pancreatic ductal adenocarcinoma by regulating mitochondrial function.NDRG4 的高甲基化介导的沉默通过调节线粒体功能促进胰腺导管腺癌。
BMB Rep. 2020 Dec;53(12):658-663. doi: 10.5483/BMBRep.2020.53.12.168.
7
N-MYC Downstream Regulated Gene 4 (), a Frequent Downregulated Gene through DNA Hypermethylation, plays a Tumor Suppressive Role in Esophageal Adenocarcinoma.N-MYC下游调控基因4(NDRG4)是一种通过DNA高甲基化频繁下调的基因,在食管腺癌中发挥肿瘤抑制作用。
Cancers (Basel). 2020 Sep 10;12(9):2573. doi: 10.3390/cancers12092573.
8
The up-regulation of NDRG1 by HIF counteracts the cancer-promoting effect of HIF in VHL-deficient clear cell renal cell carcinoma.缺氧诱导因子(HIF)上调 NDRG1 可抵消 VHL 缺陷型透明细胞肾细胞癌中 HIF 的促癌作用。
Cell Prolif. 2020 Jul;53(7):e12853. doi: 10.1111/cpr.12853. Epub 2020 Jun 14.
9
Nervous NDRGs: the N-myc downstream-regulated gene family in the central and peripheral nervous system.神经NDRGs:中枢和外周神经系统中的N-myc下游调控基因家族。
Neurogenetics. 2019 Oct;20(4):173-186. doi: 10.1007/s10048-019-00587-0. Epub 2019 Sep 4.
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GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis.GEPIA2:一个用于大规模表达谱分析和交互式分析的增强型网络服务器。
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