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锌指蛋白514在人类肿瘤中的预后及免疫作用的泛癌分析

A pan-cancer analysis of the prognostic and immunological roles of zinc finger protein 514 in human tumors.

作者信息

Zhao Shuai, Cheng Lin, Ji Xingzhao, Sun Shengnan, Liu Yi, Wan Qiang

机构信息

Shandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Shandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

出版信息

Front Oncol. 2025 Jun 17;15:1592989. doi: 10.3389/fonc.2025.1592989. eCollection 2025.

Abstract

BACKGROUND

Recent studies have highlighted the essential role of the zinc finger gene family, whose encoded proteins play a pivotal role in all stages of tumor initiation and development. Zinc Finger Protein 514 (ZNF514) is a member of the ZNF family, and its abnormal expression and prognostic value in human pan-cancer have not yet been described. The purpose of this study is to investigate the prognostic and immunological roles of ZNF514 in pan-cancer and to confirm its cancer-promoting effect in renal clear cell carcinoma.

METHODS

In our study, we utilized the Human Protein Atlas (HPA) database to determine the expression of ZNF514 in human normal and tumor tissues. We also used the Tumor Immune Estimation Resource 2.0 (TIMER 2.0) database to investigate the association between ZNF514 expression and immune checkpoint genes and immune infiltration. To detect the expression and prognostic value of ZNF514 in pan-cancers, we utilized The Cancer Genome Atlas (TCGA) or the Genotype-Tissue Expression (GTEx) databases and analyzed the data using the Kaplan-Meier plotter, GEPIA2, cBioPortal, or Xiantao software. Additionally, we obtained the protein-protein interaction network of ZNF514 from the STRING database. To validate our findings, we performed immunohistochemistry on clinical samples. Furthermore, we conducted cellular functional experiments to examine the effects of ZNF514 overexpression or knockdown on renal clear cell carcinoma cell proliferation, migration, and invasion.

RESULTS

Our study found that ZNF514 expression was elevated in tumor tissues than in normal tissues in most tumor types. Furthermore, high expression of ZNF514 was associated with poor overall survival (OS) and disease-free survival (DFS) in certain tumor types. Further analysis of ZNF514 gene mutation data revealed that ZNF514 protein is infrequently mutated in human cancers. Moreover, ZNF514 affected prognosis and was associated with the expression of multiple immune checkpoint genes and the abundance of tumor-infiltrating immune cells across multiple types of cancer. Finally, our molecular biology experiments confirmed the oncogenic effect of ZNF514 in renal clear cell carcinoma.

CONCLUSION

Our study revealed that ZNF514 may serve as an immunological and prognostic biomarker in multiple human cancers, especially in KIRC, LIHC, LUSC, and COAD.

摘要

背景

最近的研究强调了锌指基因家族的重要作用,其编码的蛋白质在肿瘤发生和发展的各个阶段都起着关键作用。锌指蛋白514(ZNF514)是锌指家族的成员,其在人类泛癌中的异常表达和预后价值尚未见报道。本研究的目的是探讨ZNF514在泛癌中的预后和免疫作用,并证实其在肾透明细胞癌中的促癌作用。

方法

在本研究中,我们利用人类蛋白质图谱(HPA)数据库来确定ZNF514在人类正常组织和肿瘤组织中的表达。我们还使用肿瘤免疫评估资源2.0(TIMER 2.0)数据库来研究ZNF514表达与免疫检查点基因和免疫浸润之间的关联。为了检测ZNF514在泛癌中的表达和预后价值,我们利用癌症基因组图谱(TCGA)或基因型-组织表达(GTEx)数据库,并使用Kaplan-Meier绘图仪、GEPIA2、cBioPortal或仙桃软件分析数据。此外,我们从STRING数据库获得了ZNF514的蛋白质-蛋白质相互作用网络。为了验证我们的发现,我们对临床样本进行了免疫组织化学检测。此外,我们进行了细胞功能实验,以研究ZNF514过表达或敲低对肾透明细胞癌细胞增殖、迁移和侵袭的影响。

结果

我们的研究发现,在大多数肿瘤类型中,肿瘤组织中ZNF514的表达高于正常组织。此外,在某些肿瘤类型中,ZNF514的高表达与较差的总生存期(OS)和无病生存期(DFS)相关。对ZNF514基因突变数据的进一步分析表明,ZNF514蛋白在人类癌症中很少发生突变。此外,ZNF514影响预后,并与多种癌症类型中多种免疫检查点基因的表达以及肿瘤浸润免疫细胞的丰度相关。最后,我们的分子生物学实验证实了ZNF514在肾透明细胞癌中的致癌作用。

结论

我们的研究表明,ZNF514可能作为多种人类癌症,尤其是肾透明细胞癌(KIRC)、肝癌(LIHC)、肺鳞癌(LUSC)和结肠癌(COAD)的免疫和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d46a/12209179/e6e2a01d4ef7/fonc-15-1592989-g001.jpg

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