Insulin-like growth factor binding protein 1 (IGFBP1) is documented as a pro- tumorigenic gene in various cancers; nevertheless, its specific function in esophageal carcinoma (ESCA) is unclear. This study used data obtained from The Cancer Genome Atlas (TCGA) to assess IGFBP1 expression, investigating its clinical outcome-related relevance, and explore its correlation in the context of ESCA tumor microenvironment. The Wilcoxon rank-sum test indicated a notable overexpression of IGFBP1 in ESCA compared to normal tissues, which was further validated via immunohistochemistry. Functional enrichment analysis identified tumor-related pathways, while ssGSEA/CIBERSORT methods linked IGFBP1 expression to altered immune infiltration. Furthermore, an investigation of single-cell data sourced from the GSE196756 data uncovered unique immune cell subsets linked to the expression of IGFBP1. The application of Cox regression alongside Kaplan-Meier survival analyses indicated that elevated levels of IGFBP1 were correlated with unfavorable outcomes in overall survival (OS), and disease-specific survival (DSS). Functional validation utilizing CCK-8 and transwell assays revealed that IGFBP1 silencing significantly suppressed the proliferative, invasive, and migratory capabilities of ESCA cell lines. Furthermore,
in vivo
analyses also presented similar results. Collectively, these results position IGFBP1 as a prognostic biomarker in ESCA, highlighting its functional involvement in tumor progression.
Hui-Juan Jiang, Jun-Ling Zhu, Zhang Lei et al.· Frontiers in Immunology· 0 citations
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.
Hui-Juan Jiang, Jun-Ling Zhu, Zhang Lei et al.· Frontiers in Oncology· 0 citations
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