Prognostic significance of ZNF695 in uterine corpus endometrial carcinoma: single-cell and immune infiltration analyses

Abstract

Background Zinc Finger Protein 695 (ZNF695) has been reported as a prognostic indicator in several cancers; however, its clinical implications and functional contributions within uterine corpus endometrial carcinoma (UCEC) have not yet been elucidated. Herein, the prognostic significance of ZNF695 in UCEC and its potential involvement in immune infiltration were examined. Methods Bioinformatics analyses were conducted utilizing The Cancer Genome Atlas (TCGA) data to evaluate ZNF695 expression, its impact on survival, and patient clinicopathological features. ZNF695 protein expression and subcellular localization were validated using immunohistochemistry (IHC) on a UCEC tissue microarray. To dissect tumor heterogeneity and immune microenvironment, single-cell RNA-seq data from the Gene Expression Omnibus (GEO) were analyzed. The immune infiltration patterns were evaluated utilizing the CIBERSORT algorithm. Three prognostic nomograms were developed to assess UCEC patient survival at the 1-, 3-, and 5-year marks. Furthermore, in vitro cellular assays were conducted to validate ZNF695 expression and its biological roles in UCEC cells via siRNA knockdown. Results ZNF695 was significantly elevated in UCEC and associated with various clinicopathological features including age, body weight, menopause status, clinical stage, and histological grade. Functional enrichment analyses indicated that ZNF695 was involved in key biological functions, including endopeptidase regulator activity, estrogen signaling pathway and MYC targets. Additionally, single-cell subgroup analysis isolated different cell populations with high ZNF695 expression, underscoring its role in tumor microenvironment. Immune infiltration analyses indicated negative correlations between ZNF695 and various immunosuppressive immune cell subtypes. Elevated ZNF695 expression was strongly correlated with unfavorable clinical outcomes in UCEC. The nomograms for overall survival (OS), disease specific survival (DSS), and progression free interval (PFI) demonstrated promising predictive efficacy, with concordance indices (C-indexes) of 0.631, 0.719, and 0.787, respectively. In vitro functional assays demonstrated that siRNA-mediated ZNF695 knockdown markedly impaired the proliferation, migration, and invasion of UCEC cells, accompanied by cell-cycle arrest and altered apoptosis. Conclusion ZNF695 serves as an independent prognostic biomarker for UCEC, with its potential as a molecular marker validated experimentally. These findings emphasize the critical role of ZNF695 in regulating the immune landscape of UCEC, warranting studies to elucidate underlying molecular mechanisms and explore its clinical translational implications.