Department of Laboratory Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Department of Urology, Foshan First People's Hospital, Foshan City, Guangdong Province, China.
BMC Med Genomics. 2024 Jun 5;17(1):153. doi: 10.1186/s12920-024-01895-7.
Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown.
Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration.
It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments.
Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.
锌指 E 盒结合同源盒 1（ZEB1）和 ZEB2 是两种与失巢凋亡相关的转录因子。这两种基因在肾透明细胞癌（KIRC）中的 mRNA 表达显著增加，与生存不良有关。同时，ZEB1 和 ZEB2 在 KIRC 中上调的机制和临床意义尚不清楚。
通过癌症基因组图谱（TCGA）数据库和基因表达综合数据库（GEO）数据库，评估了 ZEB1 和 ZEB2 的表达谱、预后价值和接收者操作特征曲线（ROC）。在 TCGA-KIRC 数据库中进一步评估了 ZEB1 和 ZEB2 与失巢凋亡的相关性。接下来，使用 miRTarBase、miRDB 和 TargetScan 预测靶向 ZEB1 和 ZEB2 的 microRNAs，利用 TCGA-KIRC 数据库辨别 microRNAs 的差异，并建立 microRNAs 与 ZEBs 之间的关联。TCGA、TIMER、TISIDB 和 TISCH 用于分析肿瘤免疫浸润。
发现 ZEB1 和 ZEB2 的表达与 KIRC 患者的组织学分级有关。Kaplan-Meier 生存分析表明，ZEB1 或 ZEB2 水平较低的 KIRC 患者的生存率显著降低。同时，ZEB1 和 ZEB2 与失巢凋亡密切相关，并受 microRNAs 调节。我们使用单变量 Cox 和 LASSO 回归分析构建了一个风险模型，以识别两个 microRNAs（hsa-miR-130b-3p 和 hsa-miR-138-5p）。此外，ZEB1 和 ZEB2 调节 KIRC 肿瘤微环境中的免疫细胞浸润。
KIRC 中 ZEB1 和 ZEB2 mRNA 的上调与失巢凋亡、细胞毒性免疫细胞浸润和患者生存结局相关。ZEB1 和 ZEB2 受 microRNAs 调节。
