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: insights into its oncogenic potential, prognostic value, and impact on immune microenvironment across cancers.

Frontiers in immunology 2025 Vol.16() p. 1591912

Tian W, Yu C, Xu X, Li J, Peng S, Sun A, Zhang S, Jiang C

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[BACKGROUND] () is a zinc finger transcription factor gene that regulates gene expression by recognizing and binding to specific DNA sequences.

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APA Tian W, Yu C, et al. (2025). : insights into its oncogenic potential, prognostic value, and impact on immune microenvironment across cancers.. Frontiers in immunology, 16, 1591912. https://doi.org/10.3389/fimmu.2025.1591912
MLA Tian W, et al.. ": insights into its oncogenic potential, prognostic value, and impact on immune microenvironment across cancers.." Frontiers in immunology, vol. 16, 2025, pp. 1591912.
PMID 40655141

Abstract

[BACKGROUND] () is a zinc finger transcription factor gene that regulates gene expression by recognizing and binding to specific DNA sequences. Preliminary studies have suggested that plays a pivotal role in the invasion and metastasis of various solid cancers. However, its role within the tumor immune microenvironment, as well as its prognostic value and potential for predicting responses to immunotherapy across different cancer types, remains inadequately explored and warrants a comprehensive systematic analysis.

[METHODS] expression levels in various cancers were obtained from the Cancer Genome Atlas (TCGA) database. The TISCH web tool analyzed expression in 32 cell types. A spatial distribution map of related to cancer tissue markers was created using the STOmics DB. A univariate Cox regression analysis was performed to evaluate 's prognostic value. The cBioPortal database helped explore potential mutations across cancer types. The TIMER2.0 database was used to study the relationship between expression and immune cell infiltration. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed to elucidate signaling pathways modulated by . Drug sensitivity testing for was done using the CellMiner, the Cancer Therapeutics Response Portal (CTRP), and the Genomics of Drug Sensitivity in Cancer (GDSC) databases. Finally, knockdown was achieved with siRNA silencing.

[RESULTS] Changes in expression are linked to the prognosis of most cancer patients. In the tumor microenvironment, is mainly found in CD4 Tconv cells and monocytes/macrophages. Studies show that is associated with cancer immunotherapy markers, immune cell infiltration, and immune modulators. Additionally, its role in immune regulation was confirmed through analysis of StromalScore, ImmuneScore, ESTIMATE, and immune infiltration. Molecular docking identified -targeted drugs, with validated effects on breast cancer and gastric cancer cell survival and migration . Lastly, the knockdown of can suppress cancer cell migration.

[CONCLUSION] Collectively, these findings underscore the pivotal role of in tumor biology and immune modulation. emerges as a promising prognostic biomarker and potential therapeutic target, offering novel avenues for cancer treatment strategies.

MeSH Terms

Humans; Tumor Microenvironment; Neoplasms; Prognosis; Kruppel-Like Transcription Factors; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Mutation; Databases, Genetic

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