ZNF114 as a prognostic biomarker associated with Wnt/EMT and immune-related features in gastric cancer
- 1Henan Provincial People’s Hospital, Henan Provincial Research Center for Precision Control Engineering of Digestive Tract Tumors
- 2Department of Gastrointestinal Surgery, People’s Hospital of Henan University, Henan Provincial People’s Hospital, School of Clinical Medicine, Henan University
- 3Department of Gastrointestinal Surgery, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital, School of Clinical Medicine, Zhengzhou University
Abstract
Objective: To investigate ZNF114 expression, clinical significance, and its role in malignant phenotypes and its associations with immune-related features in gastric cancer (GC).
Methods: ZNF114 expression and prognosis were analyzed using The Cancer Genome Atlas (TCGA) stomach adenocarcinoma (STAD) and Gene Expression Omnibus (GEO) datasets (GSE79973, GSE65801, GSE13861), and validated in an in-house cohort of six paired gastric cancer and adjacent non-tumor specimens via Western blotting and immunohistochemistry. ZNF114-knockdown GC cells were established using small interfering RNA (siRNA). Rescue experiments used an si-2-resistant ZNF114 construct in AGS and HGC-27 cells. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound healing, Transwell assays, gene set enrichment analysis (GSEA) and Western blotting were used to evaluate proliferation, apoptosis, migration, invasion and Wnt/epithelial-mesenchymal transition (EMT)-associated signaling. A xenograft model was used for in vivo validation, with Ki-67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Immune microenvironment analysis included immune-cell/signature scoring, checkpoint-landscape evaluation, tumor mutational burden (TMB) and genome-feature assessment, and exploratory drug-sensitivity prediction using oncoPredict based on GDSC2 data.
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 and invasion, and induced apoptosis. ZNF114 was associated with EMT and Wnt signaling; its silencing increased E-cadherin and decreased N-cadherin, Vimentin and the Wnt-related proteins β-catenin, c-Myc, Cyclin D1 and p-GSK3β. Re-expression of ZNF114 attenuated the knockdown-associated EMT changes and restored malignant phenotypes in rescue assays. High ZNF114 expression was associated with elevated Wnt/EMT signaling and a higher composite immune-cold index (FDR < 0.001), alongside altered non-classical checkpoint patterns, lower tumor mutational burden and predicted drug-sensitivity differences, whereas individual immune-activation features showed non-significant downward trends after multiple-testing correction. These computational findings are TCGA-based, associative and hypothesis-generating. In vivo , ZNF114 knockdown suppressed tumor growth.
Conclusion: ZNF114 is associated with malignant phenotypes and Wnt/EMT-associated remodeling. Its high expression is associated with a higher composite immune-cold index and altered immune-related transcriptomic features, supporting ZNF114 as a candidate prognostic biomarker and a candidate for future mechanistic and therapy-oriented studies.
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BibTeX
@article{li2026znf114,
title = {{ZNF114 as a prognostic biomarker associated with Wnt/EMT and immune-related features in gastric cancer}},
author = {Wenzheng Li and Zhengxuan Zhang and Yiyan Li and Aoxue Xing and Hailiang Wang and Gang Wu and Peichun Sun and Wei Zhang},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1946670},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1946670/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ZNF114 as a prognostic biomarker associated with Wnt/EMT and immune-related features in gastric cancer
AU - Wenzheng Li
AU - Zhengxuan Zhang
AU - Yiyan Li
AU - Aoxue Xing
AU - Hailiang Wang
AU - Gang Wu
AU - Peichun Sun
AU - Wei Zhang
PY - 2026
DA - 2026/10/20
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1946670
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1946670/full
AB - Objective: To investigate ZNF114 expression, clinical significance, and its role in malignant phenotypes and its associations with immune-related features in gastric cancer (GC). Methods: ZNF114 expression and prognosis were analyzed using The Cancer Genome Atlas (TCGA) stomach adenocarcinoma (STAD) and Gene Expression Omnibus (GEO) datasets (GSE79973, GSE65801, GSE13861), and validated in an in-house cohort of six paired gastric cancer and adjacent non-tumor specimens via Western blotting and immunohistochemistry. ZNF114-knockdown GC cells were established using small interfering RNA (siRNA). Rescue experiments used an si-2-resistant ZNF114 construct in AGS and HGC-27 cells. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound healing, Transwell assays, gene set enrichment analysis (GSEA) and Western blotting were used to evaluate proliferation, apoptosis, migration, invasion and Wnt/epithelial-mesenchymal transition (EMT)-associated signaling. A xenograft model was used for in vivo validation, with Ki-67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Immune microenvironment analysis included immune-cell/signature scoring, checkpoint-landscape evaluation, tumor mutational burden (TMB) and genome-feature assessment, and exploratory drug-sensitivity prediction using oncoPredict based on GDSC2 data. 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 and invasion, and induced apoptosis. ZNF114 was associated with EMT and Wnt signaling; its silencing increased E-cadherin and decreased N-cadherin, Vimentin and the Wnt-related proteins β-catenin, c-Myc, Cyclin D1 and p-GSK3β. Re-expression of ZNF114 attenuated the knockdown-associated EMT changes and restored malignant phenotypes in rescue assays. High ZNF114 expression was associated with elevated Wnt/EMT signaling and a higher composite immune-cold index (FDR < 0.001), alongside altered non-classical checkpoint patterns, lower tumor mutational burden and predicted drug-sensitivity differences, whereas individual immune-activation features showed non-significant downward trends after multiple-testing correction. These computational findings are TCGA-based, associative and hypothesis-generating. In vivo , ZNF114 knockdown suppressed tumor growth. Conclusion: ZNF114 is associated with malignant phenotypes and Wnt/EMT-associated remodeling. Its high expression is associated with a higher composite immune-cold index and altered immune-related transcriptomic features, supporting ZNF114 as a candidate prognostic biomarker and a candidate for future mechanistic and therapy-oriented studies.
SN - 2234-943X
ER -