Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, China.
BMC Cancer. 2023 Apr 3;23(1):301. doi: 10.1186/s12885-023-10779-5.
As a common malignant tumor, esophageal carcinoma (ESCA) has a low early diagnosis rate and poor prognosis. This study aimed to construct the prognostic features composed of ZNF family genes to effectively predict the prognosis of ESCA patients.
The mRNA expression matrix and clinical data were downloaded from TCGA and GEO database. Using univariate Cox analysis, lasso regression and multivariate Cox analysis, we screened six prognosis-related ZNF family genes to construct the prognostic model. We then used Kaplan-Meier plot, time-dependent receiver operating characteristic (ROC), multivariable Cox regression analysis of clinical information, and nomogram to evaluate the prognostic value within and across sets, separately and combined. We also validated the prognostic value of the six-gene signature using GSE53624 dataset. The different immune status was observed in the single sample Gene Set Enrichment Analysis (ssGSEA). Finally, real-time quantitative PCR was used to detect the expression of six prognostic ZNF genes in twelve pairs of ESCA and adjacent normal tissues.
A six prognosis-related ZNF family genes model consisted of ZNF91, ZNF586, ZNF502, ZNF865, ZNF106 and ZNF225 was identified. Multivariable Cox regression analysis revealed that six prognosis-related ZNF family genes were independent prognostic factors for overall survival of ESCA patients in TCGA and GSE53624. Further, a prognostic nomogram including the riskScore, age, gender, T, stage was constructed, and TCGA/GSE53624-based calibration plots indicated its excellent predictive performance. Drug Sensitivity and ssGSEA analysis showed that the six genes model was closely related to immune cells infiltration and could be used as a potential predictor of chemotherapy sensitivity.
We identified six prognosis-related ZNF family genes model of ESCA, which provide evidence for individualized prevention and treatment.
食管癌（ESCA）作为一种常见的恶性肿瘤，早期诊断率低，预后差。本研究旨在构建由 ZNF 家族基因组成的预后特征，以有效预测 ESCA 患者的预后。
从 TCGA 和 GEO 数据库下载 mRNA 表达矩阵和临床数据。使用单因素 Cox 分析、lasso 回归和多因素 Cox 分析，筛选出与预后相关的六个 ZNF 家族基因，构建预后模型。然后使用 Kaplan-Meier 图、时间依赖性 ROC、临床信息的多变量 Cox 回归分析以及列线图分别和联合在内部和外部数据集评估预后价值。我们还使用 GSE53624 数据集验证了六个基因特征的预后价值。在单样本基因集富集分析（ssGSEA）中观察到不同的免疫状态。最后，使用实时定量 PCR 检测 12 对 ESCA 和相邻正常组织中六个预后 ZNF 基因的表达。
鉴定出一个由 ZNF91、ZNF586、ZNF502、ZNF865、ZNF106 和 ZNF225 六个与预后相关的 ZNF 家族基因模型。多因素 Cox 回归分析显示，在 TCGA 和 GSE53624 中，六个与预后相关的 ZNF 家族基因是 ESCA 患者总生存的独立预后因素。进一步构建了包括风险评分、年龄、性别、T 分期和 N 分期的预后列线图，TCGA/GSE53624 基于校准图表明其具有良好的预测性能。药物敏感性和 ssGSEA 分析表明，该六个基因模型与免疫细胞浸润密切相关，可作为化疗敏感性的潜在预测指标。
我们确定了 ESCA 的六个与预后相关的 ZNF 家族基因模型，为个体化防治提供了依据。
