Urology Surgery, Hebei Petro China Central Hospital, Langfang 065000, China.
Precision Medicine Center, Tianjin Medical University General Hospital, Tianjin 300000, China.
Math Biosci Eng. 2022 Jan;19(2):1825-1842. doi: 10.3934/mbe.2022085. Epub 2021 Dec 17.
Recently, MYBL2 is frequently found to be overexpressed and associated with poor patient outcome in breast cancer, colorectal cancer, bladder carcinoma, hepatocellular carcinoma, neuroblastoma and acute myeloid leukemia. In view of the fact that there is an association between MYBL2 expression and the clinicopathological features of human cancers, most studies reported so far are limited in their sample size, tissue type and discrete outcomes. Furthermore, we need to verify which additional cancer entities are also affected by MYBL2 deregulation and which patients could specifically benefit from using MYBL2 as a biomarker or therapeutic target. We characterized the up-regulated expression level of MYBL2 in a large variety of human cancer via TCGA and oncomine database. Subsequently, we verified the elevated MYBL2 expression effect on clinical outcome using various databases. Then, we investigate the potential pathway in which MYBL2 may participate in and find 4 TFs (transcript factors) that may regulate MYBL2 expression using bioinformatic methods. At last, we confirmed elevated MYBL2 expression can be useful as a biomarker and potential therapeutic target of poor patient prognosis in a large variety of human cancers. Additionally, we find E2F1, E2F2, E2F7 and ZNF659 could interact with MYBL2 promotor directly or indirectly, indicating the four TFs may be the upstream regulator of MYBL2. TP53 mutation or TP53 signaling altered may lead to elevated MYBL2 expression. Our findings indicate that elevated MYBL2 expression represents a prognostic biomarker for a large number of cancers. What's more, patients with both P53 mutation and elevated MTBL2 expression showed a worse survival in PRAD and BRCA.
最近,MYBL2 在乳腺癌、结直肠癌、膀胱癌、肝细胞癌、神经母细胞瘤和急性髓系白血病中经常被发现过度表达,并与患者预后不良有关。鉴于 MYBL2 表达与人类癌症的临床病理特征之间存在关联,迄今为止大多数研究的样本量、组织类型和离散结果都受到限制。此外,我们需要验证哪些其他癌症实体也受到 MYBL2 失调的影响,以及哪些患者可以特别受益于将 MYBL2 用作生物标志物或治疗靶点。我们通过 TCGA 和 oncomine 数据库对大量人类癌症中 MYBL2 的上调表达水平进行了表征。随后,我们使用各种数据库验证了升高的 MYBL2 表达对临床结局的影响。然后,我们研究了 MYBL2 可能参与的潜在途径,并使用生物信息学方法发现了 4 个可能调节 MYBL2 表达的转录因子 (TFs)。最后,我们证实升高的 MYBL2 表达可以作为多种人类癌症中患者预后不良的有用生物标志物和潜在治疗靶点。此外,我们发现 E2F1、E2F2、E2F7 和 ZNF659 可以直接或间接与 MYBL2 启动子相互作用,表明这四个 TF 可能是 MYBL2 的上游调节剂。TP53 突变或 TP53 信号改变可能导致 MYBL2 表达升高。我们的研究结果表明,升高的 MYBL2 表达代表了大量癌症的预后生物标志物。更重要的是,在 PRAD 和 BRCA 中,同时具有 P53 突变和升高的 MTBL2 表达的患者生存更差。