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

## TL;DR

This study shows that lower levels of a protein called EZF in lung cancer tissues are linked to worse patient outcomes and immune system changes, suggesting it could help predict cancer progression.

## Contribution

EZF is identified as a novel prognostic biomarker in lung adenocarcinoma with dual roles in tumor progression and immune regulation.

## Key findings

- EZF expression is significantly reduced in lung cancer tissues compared to normal tissues.
- EZF downregulation correlates with advanced tumor stages and poor survival outcomes.
- EZF is linked to immune cell infiltration and hypomethylation, suggesting roles in immune modulation.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s41065-025-00476-7.