Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Department of Oncology, Shaanxi Provincial People's Hospital, Xi'an 710068, Shaanxi, China.
Department of Radiotherapy, Shaanxi Provincial People's Hospital, Xi'an 710068, Shaanxi, China.
Gene. 2022 Jun 20;828:146471. doi: 10.1016/j.gene.2022.146471. Epub 2022 Apr 2.
Zinc finger protein family is the largest transcription factor family in the human genome. Studies have shown that the aberrant expression of zinc finger protein (ZNF) had a potential role in tumorigenesis. However, due to the high complexity of the ZNF family genes, the role of the ZNF family genes in breast cancer (BRCA) is still lacking in systematic understanding.
In the study, we aim to understand the expression profile, prognostic value, immune invasion pattern, tumor microenvironment, epigenetic and pathway relationships, and drug sensitivity of ZNFs using multi-omics data from public databases.
We focused on six members of ZNFs, which were upregulated in a variety of cancers. Notably, ZNF750 and ZNF224 were lower expressed in BRCA, and their expressions were significantly associated with BRCA prognosis. We confirmed the observations obtained by analyzing the clinic-pathological data. Otherwise, the expressions of ZNFs were significantly related to stromal and immune scores, and was significantly different among different immune subtypes in BRCA. Here, we found down-regulated methylation of ZNF217 and ZNF750. The relationship between methylation and survival showed the survival was worse for hypo-methylation of ZNF750 in BRCA, which is consistent with the correlation of high expression of ZNF750 in BRCA with worse survival.
Collectively, our results provide clues for a better understanding of the characterization of ZNF family genes in BRCA from a multi-omics perspective and show their potential for use as new tumor markers and therapeutic targets.
锌指蛋白家族是人类基因组中最大的转录因子家族。研究表明，锌指蛋白（ZNF）的异常表达在肿瘤发生中具有潜在作用。然而，由于 ZNF 家族基因的复杂性很高，ZNF 家族基因在乳腺癌（BRCA）中的作用仍缺乏系统的认识。
在这项研究中，我们旨在使用公共数据库中的多组学数据来了解 ZNF 家族基因的表达谱、预后价值、免疫浸润模式、肿瘤微环境、表观遗传和途径关系以及药物敏感性。
我们专注于 ZNFs 的六个成员，这些成员在多种癌症中上调。值得注意的是，ZNF750 和 ZNF224 在 BRCA 中表达较低，其表达与 BRCA 预后显著相关。我们通过分析临床病理数据证实了观察结果。此外，ZNFs 的表达与基质和免疫评分显著相关，并且在 BRCA 中的不同免疫亚型之间存在显著差异。在这里，我们发现 ZNF217 和 ZNF750 的甲基化下调。甲基化与生存之间的关系表明，BRCA 中 ZNF750 的低甲基化预示着生存较差，这与 BRCA 中 ZNF750 的高表达与较差的生存相关。
总之，我们的结果从多组学角度为更好地理解 BRCA 中 ZNF 家族基因的特征提供了线索，并显示了它们作为新的肿瘤标志物和治疗靶点的潜力。
