Work

ZNF114 as a prognostic biomarker associated with Wnt/EMT and immune-related features in gastric cancer

Year: 2026

Type: article

Abstract: Objective To investigate ZNF114 expression, clinical significance, and its role in malignant phenotypes and the tumor immune microenvironment in gastric cancer (GC). Methods ZNF114 expression and prognosis were analyzed using TCGA-STAD and GEO datasets (GSE79973, GSE65801, GSE13861), and validated in clinical samples via Western blotting and immunohistochemistry. ZNF114-knockdown GC cells were established using siRNA. CCK-8, colony formation, flow cytometry, and Transwell assays assessed proliferation, apoptosis, migration, and invasion. EMT association was evaluated using CancerSEA, GSEA, and Western blotting. A xenograft model was used for in vivo validation, with Ki-67 and TUNEL staining. Immune microenvironment analysis included ssGSEA, cancer–immunity cycle, immune subtypes, and MSI status. Results ZNF114 was overexpressed in GC tissues and cell lines, with high expression linked to poor survival and adverse clinicopathology. ZNF114 knockdown inhibited proliferation, migration, invasion, and induced apoptosis. Mechanistically, ZNF114 positively correlated with EMT; its silencing upregulated E-cadherin, downregulated N-cadherin and Vimentin. High ZNF114 associated with immunosuppressive features (reduced CD8 + T cells/NK cells, low cytolytic activity) and low-immunogenicity subtypes (MSS, non-C2 immune subtypes). In vivo, ZNF114 knockdown suppressed tumor growth. Conclusion ZNF114 acts as an oncogenic factor in GC by promoting EMT and shaping an immunosuppressive microenvironment, serving as a potential prognostic biomarker and therapeutic target.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1946670