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基于E26转录因子构建胃癌预后特征并鉴定新型癌基因ELK3。

Construction of gastric cancer prognostic signature based on the E26 transcription factor and the identification of novel oncogene ELK3.

作者信息

Liu Chenxi, Zhou Liqiang, Chen Zhiqing

机构信息

School of Optometry, Jiangxi Medical College, Nanchang University Nanchang 330006, Jiangxi, P. R. China.

Department of General Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang 330006, Jiangxi, P. R. China.

出版信息

Am J Cancer Res. 2024 Apr 15;14(4):1831-1849. doi: 10.62347/RVBP7871. eCollection 2024.

Abstract

The aim of the present study was to investigate the function of 29 E26 (ETS) transcription factor families in gastric cancer (GC) and determine their association with prognosis. Our analysis of the expression of the ETS family revealed that 28 genes were dysregulated in GC, and that their expression was associated with multiple clinicopathological features (P<0.05). Based on the expression signature of the ETS family, consensus clustering was performed to generate two gastric cancer subtypes. These subtypes exhibited differences in overall survival (OS, P = 0.161), disease-free survival (DFS, P<0.05) and GC grade (P<0.01). Functional enrichment analysis of the target genes associated with the ETS family indicated that these genes primarily contribute to functions that facilitate tumor progression. A systematic statistical analysis was used to construct a prognostic model related to OS and DFS in association with the ETS family. This model demonstrated that the maximum area under the curve (AUC) values for predicting OS and DFS were 0.729 and 0.670, respectively, establishing ETS as an independent prognostic factor for GC Furthermore, a nomogram was created from the prognostic signature, and its predictive accuracy was confirmed by a calibration curve. Finally, the expression and prognostic significance of the six genes comprising the model were also examined. Among these, ELK3 was found to be significantly overexpressed in GC clinical samples. Subsequent and studies verified that ELK3 regulates GC proliferation and metastasis, highlighting its potential as a therapeutic target for gastric cancer.

摘要

本研究的目的是探讨29个E26(ETS)转录因子家族在胃癌(GC)中的功能,并确定它们与预后的关系。我们对ETS家族表达的分析表明,28个基因在GC中表达失调,且其表达与多种临床病理特征相关(P<0.05)。基于ETS家族的表达特征,进行一致性聚类以生成两种胃癌亚型。这些亚型在总生存期(OS,P = 0.161)、无病生存期(DFS,P<0.05)和GC分级(P<0.01)方面存在差异。对与ETS家族相关的靶基因进行功能富集分析表明,这些基因主要促成促进肿瘤进展的功能。使用系统的统计分析构建与ETS家族相关的OS和DFS预后模型。该模型表明,预测OS和DFS的最大曲线下面积(AUC)值分别为0.729和0.670,确立ETS为GC的独立预后因素。此外,根据预后特征创建了列线图,并通过校准曲线证实了其预测准确性。最后,还检测了构成该模型的六个基因的表达及预后意义。其中,发现ELK3在GC临床样本中显著过表达。随后的研究证实ELK3调节GC的增殖和转移,突出了其作为胃癌治疗靶点的潜力。

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