PDF(Pubmed)
Abstract：
There is evidence from multiple studies that dysregulation of the Eyes Absent (EYA) protein plays multiple roles in many cancers. Despite this, little is known about the prognostic significance of the EYAs family in clear cell renal cell carcinoma (ccRCC). We systematically analyzed the value of EYAs in Clear Cell Renal Cell Carcinoma. Our analysis included examining transcriptional levels, mutations, methylated modifications, co-expression, protein-protein interactions (PPIs), immune infiltration, single-cell sequencing, drug sensitivity, and prognostic values. We based our analysis on data from several databases, including the Cancer Genome Atlas database (TCGA), the Gene Expression Omnibus database (GEO), UALCAN, TIMER, Gene Expression Profiling Interactive Analysis (GEPIA), STRING, cBioPortal and GSCALite. In patients with ccRCC, the EYA1 gene was significantly highly expressed, while the expression of EYA2/3/4 genes showed the opposite trend. The level of expression of the EYA1/3/4 gene was significantly correlated with the prognosis and clinicopathological parameters of ccRCC patients. Univariate and multifactorial Cox regression analyses revealed EYA1/3 as an independent prognostic factor for ccRCC, establishing nomogram line plots with good predictive power. Meanwhile, the number of mutations in EYAs was also significantly correlated with poor overall survival (OS) and progression-free survival (PFS) of patients with ccRCC. Mechanistically, EYAs genes play an essential role in a wide range of biological processes such as DNA metabolism and double-strand break repair in ccRCC. The majority of EYAs members were related to the infiltration of immune cells, drug sensitivity, and methylation levels. Furthermore, our experiment confirmed that EYA1 gene expression was upregulated, and EYA2/3/4 showed low expression in ccRCC. The increased expression of EYA1 might play an important role in ccRCC oncogenesis, and the decreased expression of EYA3/4 could function as a tumor suppressor, suggesting EYA1/3/4 might serve as valuable prognostic markers and potential new therapeutic targets for ccRCC.
摘要：
来自多项研究的证据表明，缺眼（EYA）蛋白的失调在许多癌症中起着多种作用。尽管如此,关于EYAs家族在透明细胞肾细胞癌（ccRCC）中的预后意义知之甚少。我们系统分析了EYAs在肾透明细胞癌中的价值。我们的分析包括检查转录水平，突变,甲基化修饰，共表达，蛋白质-蛋白质相互作用(PPIs)，免疫浸润，单细胞测序，药物敏感性,和预后价值。我们的分析基于几个数据库的数据，包括癌症基因组图谱数据库（TCGA），基因表达综合数据库(GEO)，UALCAN,TIMER,基因表达谱交互式分析（GEPIA），STRING,cBioPortal和GSCALite。在ccRCC患者中，EYA1基因显著高表达，而EYA2/3/4基因的表达则呈现相反的趋势。EYA1/3/4基因的表达水平与ccRCC患者的预后和临床病理参数显着相关。单因素和多因素Cox回归分析显示EYA1/3是ccRCC的独立预后因素。建立具有良好预测能力的列线图。同时,EYAs中的突变数量也与ccRCC患者的不良总生存期(OS)和无进展生存期(PFS)显著相关.机械上,EYAs基因在ccRCC的DNA代谢和双链断裂修复等多种生物学过程中起着至关重要的作用。大多数EYAs成员与免疫细胞浸润有关，药物敏感性,和甲基化水平。此外，我们的实验证实EYA1基因表达上调，EYA2/3/4在ccRCC中呈低表达。EYA1的表达增加可能在ccRCC的发生中起重要作用。EYA3/4的表达降低可能是一种肿瘤抑制因子，提示EYA1/3/4可能作为ccRCC有价值的预后标志物和潜在的新治疗靶点。
