Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications.

IF 2.7 3区生物学

Hereditas Pub Date : 2025-06-18 DOI:10.1186/s41065-025-00476-7

Xiaofen Wen, Jianling Zhu, Didi Xi, Minna Chen, De Zeng, Wenwu Xue, Danxia Lin, Jiaxin Shen

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引用次数: 0

Abstract

Objective: This study aimed to evaluate the prognostic significance of epithelial zinc finger protein (EZF/KLF4) in lung adenocarcinoma (LAC) and explore its potential roles in tumor progression and immune regulation.

Methods and materials: EZF expression and its associations with clinical characteristics were analyzed using TCGA and GEO datasets, and validated by immunohistochemistry in 25 paired LAC and adjacent normal tissues. Mechanistic insights were investigated through protein-protein interaction networks, gene set enrichment analysis (GSEA), DNA methylation profiling, and immune cell infiltration analysis via single-sample GSEA. A prognostic nomogram incorporating EZF expression, pT and pN stages, and residual tumor status was constructed using Cox regression modeling.

Results: EZF expression was significantly downregulated in LAC tissues compared to normal tissues across multiple cohorts (P < 0.001), yet paradoxically associated with advanced tumor stages and worse overall, disease-specific, and progression-free survival. Functional analyses revealed EZF-associated pathways enriched in immune modulation. EZF expression correlated strongly with infiltrating immune cells, including NK cells, eosinophils, mast cells, and neutrophils. Hypomethylation of the EZF promoter was linked to poor prognosis. The constructed nomogram exhibited strong predictive accuracy for patient outcomes.

Conclusion: EZF functions as a context-dependent regulator in LAC and may act as a prognostic biomarker by modulating tumor-immune interactions. These findings offer novel insights into the integration of molecular and immune features for personalized risk stratification and therapeutic guidance in LAC.

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肺腺癌上皮锌指蛋白：具有分子和临床意义的预后生物标志物。

目的：本研究旨在评价上皮锌指蛋白（EZF/KLF4）在肺腺癌（LAC）中的预后意义，并探讨其在肿瘤进展和免疫调节中的潜在作用。方法和材料：采用TCGA和GEO数据集分析EZF表达及其与临床特征的相关性，并通过免疫组化方法验证25对LAC和邻近正常组织的EZF表达。通过蛋白质相互作用网络、基因集富集分析（GSEA）、DNA甲基化分析和单样本GSEA免疫细胞浸润分析来研究其机制。采用Cox回归模型构建EZF表达、pT和pN分期及残余肿瘤状态的预后图。结果：在多个队列中，与正常组织相比，LAC组织中EZF的表达显著下调(P结论：EZF在LAC中作为一种环境依赖的调节剂，可能通过调节肿瘤-免疫相互作用作为预后生物标志物。这些发现为LAC的个性化风险分层和治疗指导提供了分子和免疫特征整合的新见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.