Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, 710061, Shaanxi, China.
Department of Gerontological Surgery, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, 710061, Shaanxi, China.
BMC Cancer. 2021 Apr 7;21(1):367. doi: 10.1186/s12885-021-08112-z.
An important mechanism that promoter methylation-mediated gene silencing for gene inactivation is identified in human tumorigenesis. Methylated genes have been found in breast cancer (BC) and beneficial biomarkers for early diagnosis. Prognostic assessment of breast cancer remain little known. Zinc finger protein 132 (ZNF132) is downregulated by promoter methylation in prostate cancer and esophageal squamous cell carcinoma. However, no study provides information on the status of ZNF132, analyzes diagnosis and prognostic significance of ZNF132 in BC.
In the present study, the expression of ZNF132 mRNA and protein level was determined based on the Cancer Genome Atlas (TCGA) RNA-Seq database and clinical samples analysis and multiple cancer cell lines verification. P rognostic significance of ZNF132 in BC was assessed using the Kaplan-Meier plotter. Molecular mechanisms exploration of ZNF132 in BC was performed using the multiple bioinformatic tools. Hypermethylated status of ZNF132 in BC cell lines was confirmed via Methylation specific polymerase chain reaction (MSP) analysis.
The expression of ZNF132 both the mRNA and protein levels was downregulated in BC tissues. These results were obtained based on TCGA database and clinical sample analysis. Survival analysis from the Kaplan-Meier plotter revealed that the lower level of ZNF132 was associated with a shorter Relapse Free Survival (RFS) time. Receiver operating characteristic curve (ROC) of 0.887 confirmed ZNF132 had powerful sensitivity and specificity to distinguish between BC and adjacent normal tissues. Bioinformatic analysis showed that 6% ((58/960)) alterations of ZNF132 were identified from cBioPortal. ZNF132 participated in multiple biological pathways based on the Gene Set Enrichment Analysis (GSEA) database including the regulation of cell cycle and glycolysis. Finally, MSP analysis demonstrated that ZNF132 was hypermethylated in a panel of breast cancer cell lines and 5-aza-2'-deoxycytidine (5-Aza-dC) treatment restored ZNF132 expression in partial cell lines.
Results revealed that hypermethylation of ZNF132 contributed to its downregulated expression and could be identified as a new diagnostic and prognostic marker in BC.
启动子甲基化介导的基因沉默是人类肿瘤发生中基因失活的一个重要机制。在乳腺癌（BC）中已经发现了甲基化基因，它们是早期诊断的有益生物标志物。乳腺癌的预后评估仍知之甚少。锌指蛋白 132（ZNF132）在前列腺癌和食管鳞状细胞癌中因启动子甲基化而下调。然而，尚无研究提供 ZNF132 的状态信息，也未分析 ZNF132 在 BC 中的诊断和预后意义。
本研究基于癌症基因组图谱（TCGA）RNA-Seq 数据库和临床样本分析以及多个癌细胞系验证，确定 ZNF132mRNA 和蛋白水平的表达。使用 Kaplan-Meier 绘谱器评估 ZNF132 在 BC 中的预后意义。使用多个生物信息学工具探索 ZNF132 在 BC 中的分子机制。通过甲基化特异性聚合酶链反应（MSP）分析确认 BC 细胞系中 ZNF132 的超甲基化状态。
BC 组织中 ZNF132 的 mRNA 和蛋白水平表达均下调。这些结果基于 TCGA 数据库和临床样本分析得出。Kaplan-Meier 绘谱器的生存分析显示，ZNF132 水平较低与较短的无复发生存时间（RFS）相关。ROC 曲线（0.887）证实 ZNF132 具有强大的敏感性和特异性，可区分 BC 和相邻正常组织。基于 cBioPortal 的生物信息学分析显示，ZNF132 有 6%（（58/960））的改变。基于基因集富集分析（GSEA）数据库，ZNF132 参与了多个生物学途径，包括细胞周期和糖酵解的调节。最后，MSP 分析表明 ZNF132 在一组乳腺癌细胞系中呈高甲基化状态，5-氮杂-2'-脱氧胞苷（5-Aza-dC）处理可在部分细胞系中恢复 ZNF132 的表达。
结果表明，ZNF132 的高甲基化导致其下调表达，可作为 BC 的新诊断和预后标志物。
