Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications
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 ch...
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BMC
2025-06-01
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| Series: | Hereditas |
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| Online Access: | https://doi.org/10.1186/s41065-025-00476-7 |
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| author | Xiaofen Wen Jianling Zhu Didi Xi Minna Chen De Zeng Wenwu Xue Danxia Lin Jiaxin Shen |
| author_facet | Xiaofen Wen Jianling Zhu Didi Xi Minna Chen De Zeng Wenwu Xue Danxia Lin Jiaxin Shen |
| author_sort | Xiaofen Wen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dbea06f7df064042aafd2c2a9365ed37 |
| institution | Kabale University |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Hereditas |
| spelling | doaj-art-dbea06f7df064042aafd2c2a9365ed372025-08-20T03:47:14ZengBMCHereditas1601-52232025-06-01162111810.1186/s41065-025-00476-7Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implicationsXiaofen Wen0Jianling Zhu1Didi Xi2Minna Chen3De Zeng4Wenwu Xue5Danxia Lin6Jiaxin Shen7Department of Medical Oncology, Cancer Hospital of Shantou University Medical CollegeDepartment of Pathology, Cancer Hospital of Shantou University Medical CollegeDepartment of Oncology and Hematology, Dongguan Binhai Bay Central HospitalDepartment of Medical Oncology, Cancer Hospital of Shantou University Medical CollegeDepartment of Medical Oncology, Cancer Hospital of Shantou University Medical CollegeDepartment of Medical Oncology, Cancer Hospital of Shantou University Medical CollegeDepartment of Medical Oncology, Cancer Hospital of Shantou University Medical CollegeDepartment of Hematology, The First Affiliated Hospital of Shantou University Medical CollegeAbstract 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.https://doi.org/10.1186/s41065-025-00476-7EZF/KLF4Prognostic MarkerLung AdenocarcinomaTumor ImmunityNomogram |
| spellingShingle | Xiaofen Wen Jianling Zhu Didi Xi Minna Chen De Zeng Wenwu Xue Danxia Lin Jiaxin Shen Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications Hereditas EZF/KLF4 Prognostic Marker Lung Adenocarcinoma Tumor Immunity Nomogram |
| title | Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications |
| title_full | Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications |
| title_fullStr | Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications |
| title_full_unstemmed | Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications |
| title_short | Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications |
| title_sort | epithelial zinc finger protein in lung adenocarcinoma prognostic biomarker with molecular and clinical implications |
| topic | EZF/KLF4 Prognostic Marker Lung Adenocarcinoma Tumor Immunity Nomogram |
| url | https://doi.org/10.1186/s41065-025-00476-7 |
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