Lv Zhengtong, Qi Lin, Hu Xiheng, Mo Miao, Jiang Huichuan, Fan Benyi, Li Yuan
Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Front Mol Biosci. 2021 Feb 16;8:631067. doi: 10.3389/fmolb.2021.631067. eCollection 2021.
As a transcription factor, Zinc finger protein ZIC2 can interact with various DNAs and proteins. Current studies have shown that ZIC2 plays an oncogene role in various cancers. In this study, we systematically characterize the prevalence and predictive value of ZIC2 expression across multiple cancer types. We mined several public databases, including Oncomine, the Cancer Genome Atlas (TCGA), cBioPortal, Kaplan-Meier Plotter and PrognoScan to evaluated the differentially expressed ZIC2 between tumor samples and normal control samples in pan-cancner, and then explored the association between ZIC2 expression and patient survival, prognosis and clinicopathologic stage. We also analyzed the relationship between tumor mutation burden (TMB), microsatellite instability (MSI), tumor microenvironment, tumor- and immune-related genes and ZIC2 expression. Finally, we explored the potential signaling pathway mechanism through gene set enrichment analysis (GSEA). ZIC2 expression was higher in most cancer tissues compared with adjacent normal tissues. High ZIC2 expression was associated with worse prognosis and a higher clinicopathologic stage. ZIC2 expression was strongly associated with the TMB, MSI, tumor microenvironment and tumor- and immune-related genes. The GSEA revealed that multiple tumor- and immune-related pathways were differentially enriched in ZIC2 high or low expression phenotype. ZIC2 expression may be a potential prognostic molecular biomarker of poor survival in pan-cancer and may act as an oncogene with a strong effect in the processes of tumorigenesis and progression.
作为一种转录因子，锌指蛋白ZIC2可与多种DNA和蛋白质相互作用。目前的研究表明，ZIC2在多种癌症中发挥癌基因作用。在本研究中，我们系统地描述了ZIC2在多种癌症类型中的表达情况及其预测价值。我们挖掘了多个公共数据库，包括Oncomine、癌症基因组图谱（TCGA）、cBioPortal、Kaplan-Meier Plotter和PrognoScan，以评估泛癌中肿瘤样本与正常对照样本之间ZIC2的差异表达，然后探讨ZIC2表达与患者生存、预后及临床病理分期之间的关联。我们还分析了肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、肿瘤微环境、肿瘤及免疫相关基因与ZIC2表达之间的关系。最后，我们通过基因集富集分析（GSEA）探索潜在的信号通路机制。与相邻正常组织相比，大多数癌症组织中ZIC2表达更高。ZIC2高表达与较差的预后和更高的临床病理分期相关。ZIC2表达与TMB、MSI、肿瘤微环境以及肿瘤和免疫相关基因密切相关。GSEA显示，多种肿瘤和免疫相关通路在ZIC2高表达或低表达表型中存在差异富集。ZIC2表达可能是泛癌中生存不良的潜在预后分子生物标志物，并且可能在肿瘤发生和进展过程中作为一种具有强大作用的癌基因发挥作用。
