{"title":"Zinc finger protein-associated gene signature serves as a potential predictor for prognosis and therapeutic response in lung adenocarcinoma","authors":"Mi Zou, Guangda Zheng, Yanju Bao","doi":"10.1007/s00726-026-03528-y","DOIUrl":null,"url":null,"abstract":"<div><p>Zinc finger proteins (ZNFs), characterized by zinc ion-binding domains, participate in cell proliferation, differentiation, and metastasis in lung adenocarcinoma (LUAD). However, associations between ZNFs-related genes and clinical outcomes, immune cell infiltration, and immunotherapy remain unclear. To explore feasibility of using ZNFs-related genes as prognostic tools for LUAD risk stratification. Retrospective analyses were conducted utilizing data from TCGA and GSE26939. After screening differentially expressed ZNFs, regression analyses were performed to construct prognostic signature. Enrichment analysis identified biological processes and pathways involved in signature genes, while immune landscape was examined by multiple algorithms. The drug sensitivity analysis identified potential candidate drugs related to the signature genes. Cell experiments indicated the function of the key risk gene CTCFL in promoting the malignant behavior of LUAD cells. A prognostic signature comprising 12 ZNFs-related genes (CBFA2T3, CTCFL, GFI1B, IGF2BP1, RIMS2, TRIM29, TRIML2, ZIC2, ZNF208, KLF10, ZNF750, and ZNF257) stratified LUAD patients into two risk groups, demonstrating robust performance in predicting clinical outcomes. These genes were significantly enriched in epidermal development, intermediate filament cytoskeleton, endopeptidase inhibitor activity, hormone activity, and neuroactive ligand-receptor interactions. Low-risk patients exhibited higher levels of immune cell infiltration (e.g., DCs, B cells, and neutrophils) and superior responses to immunotherapy (anti-CTLA-4 and PD-1/CTLA-4 dual blockade). Possible therapeutic compounds for LUAD patients included SHP-099, Dimethylfasudil, EMD-534085, and PF-2771. The expression of CTCFL enhanced the malignant cellular behavior in LUAD. ZNFs-related gene signature provides predictive insights into LUAD patient survival, immune cell infiltration, and immune checkpoint blockade therapy, serving as a valuable tool to guide clinical decision-making.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"58 1","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-026-03528-y.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Amino Acids","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s00726-026-03528-y","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/9/17 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Zinc finger proteins (ZNFs), characterized by zinc ion-binding domains, participate in cell proliferation, differentiation, and metastasis in lung adenocarcinoma (LUAD). However, associations between ZNFs-related genes and clinical outcomes, immune cell infiltration, and immunotherapy remain unclear. To explore feasibility of using ZNFs-related genes as prognostic tools for LUAD risk stratification. Retrospective analyses were conducted utilizing data from TCGA and GSE26939. After screening differentially expressed ZNFs, regression analyses were performed to construct prognostic signature. Enrichment analysis identified biological processes and pathways involved in signature genes, while immune landscape was examined by multiple algorithms. The drug sensitivity analysis identified potential candidate drugs related to the signature genes. Cell experiments indicated the function of the key risk gene CTCFL in promoting the malignant behavior of LUAD cells. A prognostic signature comprising 12 ZNFs-related genes (CBFA2T3, CTCFL, GFI1B, IGF2BP1, RIMS2, TRIM29, TRIML2, ZIC2, ZNF208, KLF10, ZNF750, and ZNF257) stratified LUAD patients into two risk groups, demonstrating robust performance in predicting clinical outcomes. These genes were significantly enriched in epidermal development, intermediate filament cytoskeleton, endopeptidase inhibitor activity, hormone activity, and neuroactive ligand-receptor interactions. Low-risk patients exhibited higher levels of immune cell infiltration (e.g., DCs, B cells, and neutrophils) and superior responses to immunotherapy (anti-CTLA-4 and PD-1/CTLA-4 dual blockade). Possible therapeutic compounds for LUAD patients included SHP-099, Dimethylfasudil, EMD-534085, and PF-2771. The expression of CTCFL enhanced the malignant cellular behavior in LUAD. ZNFs-related gene signature provides predictive insights into LUAD patient survival, immune cell infiltration, and immune checkpoint blockade therapy, serving as a valuable tool to guide clinical decision-making.
期刊介绍：
Amino Acids publishes contributions from all fields of amino acid and protein research: analysis, separation, synthesis, biosynthesis, cross linking amino acids, racemization/enantiomers, modification of amino acids as phosphorylation, methylation, acetylation, glycosylation and nonenzymatic glycosylation, new roles for amino acids in physiology and pathophysiology, biology, amino acid analogues and derivatives, polyamines, radiated amino acids, peptides, stable isotopes and isotopes of amino acids. Applications in medicine, food chemistry, nutrition, gastroenterology, nephrology, neurochemistry, pharmacology, excitatory amino acids are just some of the topics covered. Fields of interest include: Biochemistry, food chemistry, nutrition, neurology, psychiatry, pharmacology, nephrology, gastroenterology, microbiology
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