锌指蛋白419在人类癌症中致癌作用的泛癌分析。
A pan-cancer analysis of the oncogenic role of zinc finger protein 419 in human cancer.
作者信息
Zhu Weizhen, Feng Dechao, Shi Xu, Li Dengxiong, Wei Qiang, Yang Lu
机构信息
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
出版信息
Front Oncol. 2022 Dec 12;12:1042118. doi: 10.3389/fonc.2022.1042118. eCollection 2022.
BACKGROUND
As a ferroptosis-related gene, the polymorphism of zinc finger protein 419 (ZNF419) at the splice donor site may generate renal cell carcinoma-associated novel minor histocompatibility antigen ZAPHIR. However, the role of ZNF419 in prognosis and immunology in human tumors remains largely unknown. This study aimed to visualize the prognostic landscape of ZNF419 at pan-cancer level and explore the relationship between ZNF419 expression and the tumor immune microenvironment.
METHOD
Pan-cancer and mutation data were downloaded from TCGA databases and analyzed through R (version 3.6.4) and its suitable packages. Differential ZNF419 expression and prognosis were analyzed. Correlations with ferroptosis-related genes, pathway analysis, tumor stemness, heterogeneity, mutation landscape, and RNA modifications were also explored. The relationships between ZNF419 expression and tumor immunity were investigated through the TIMER and ESTIMATE methods.
RESULT
ZNF419 was differentially expressed between tumor and normal samples and was associated with overall survival, disease-specific survival and progression-free interval for STES, KIRC, LIHC, LUSC, PRAD, and BLCA. We found the interaction between ZNF419 and FANCD2 might involve in ferroptosis in pan-cancer level. In addition, the mutation frequencies of STES, KIRC, LIHC, LUSC, PRAD, and BLCA were 1.5%, 0.3%, 0.3%, 1.9%, 0.2%, and 0.7%, respectively. We detected that the expression of ZNF419 was closely correlated with most immune checkpoint genes and immune regulatory genes. Furthermore, we found that the ZNF419 expression level was negatively related to the immune score in the six cancers mentioned above. The expression of ZNF419 was significantly associated with various infiltrating immune cells, such as CD4+ T cells, CD8+ T cells, and macrophages in patients with KIRC, PRAD, and LUSC but was only significantly related to macrophages in BLCA patients.
CONCLUSION
ZNF419 might serve as a potential prognostic and immunological pan-cancer biomarker, especially for KIRC, LIHC, LUSC, PRAD, and BLCA.
背景
作为一种铁死亡相关基因，锌指蛋白419（ZNF419）在剪接供体位点的多态性可能产生与肾细胞癌相关的新型次要组织相容性抗原ZAPHIR。然而，ZNF419在人类肿瘤预后和免疫学中的作用仍 largely未知。本研究旨在在泛癌水平上可视化ZNF419的预后格局，并探索ZNF419表达与肿瘤免疫微环境之间的关系。
方法
从TCGA数据库下载泛癌和突变数据，并通过R（版本3.6.4）及其合适的软件包进行分析。分析ZNF419的差异表达和预后。还探索了与铁死亡相关基因的相关性、通路分析、肿瘤干性、异质性、突变格局和RNA修饰。通过TIMER和ESTIMATE方法研究ZNF419表达与肿瘤免疫的关系。
结果
ZNF419在肿瘤和正常样本之间存在差异表达，并且与STES、KIRC、LIHC、LUSC、PRAD和BLCA的总生存期、疾病特异性生存期和无进展生存期相关。我们发现在泛癌水平上ZNF419与FANCD2之间的相互作用可能参与铁死亡。此外，STES、KIRC、LIHC、LUSC、PRAD和BLCA的突变频率分别为1.5%、0.3%、0.3%、1.9%、0.2%和0.7%。我们检测到ZNF419的表达与大多数免疫检查点基因和免疫调节基因密切相关。此外，我们发现ZNF419表达水平与上述六种癌症的免疫评分呈负相关。ZNF419的表达与各种浸润性免疫细胞显著相关，如KIRC、PRAD和LUSC患者中的CD4 + T细胞、CD8 + T细胞和巨噬细胞，但仅与BLCA患者中的巨噬细胞显著相关。
结论
ZNF419可能作为一种潜在的预后和免疫泛癌生物标志物，尤其是对于KIRC、LIHC、LUSC、PRAD和BLCA。
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