Pan-Cancer Analysis of Tumor Suppressor ZNF132 Reveals Its Diagnostic and Prognostic Significance with Immunomodulatory Implications in Colorectal Cancer

Background: Zinc finger protein 132 (ZNF132) has emerged as a potential tumor suppressor, with its dysregulation closely associated with the initiation and progression of various malignancies. However, a comprehensive assessment of ZNF132's expression patterns across diverse cancer types, its clinical prognostic implications, and its immunoregulatory role in colorectal cancer remains insufficiently characterized. This study aims to elucidate the biological functions of ZNF132 within the context of colorectal cancer. Methods: We utilized transcriptomic data from 33 cancer types obtained from The Cancer Genome Atlas (TCGA) and the TCGA-COADREAD dataset to systematically analyze the expression characteristics of ZNF132 and its differential expression in colorectal cancer. Validation of protein expression was conducted using data from the Human Protein Atlas (HPA). The relationship between ZNF132 and immune infiltration was examined through single-sample gene set enrichment analysis (ssGSEA) and Spearman correlation analysis. We evaluated the diagnostic, prognostic, and independent risk prediction capabilities of ZNF132 using receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and multivariable Cox regression models. Additionally, we explored the biological pathways associated with ZNF132-related differentially expressed genes through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), supplemented by in vitro experiments to investigate the functional roles of ZNF132 in colorectal cancer. Results: Pan-cancer analysis demonstrated a significant downregulation of ZNF132 in colorectal and rectal cancers, accompanied by reduced protein levels in colorectal cancer tissues. Immune infiltration analysis revealed significant correlations between ZNF132 and various immune cell subtypes in colorectal cancer, notably a negative correlation with Th17 cells and NK CD56bright cells, while exhibiting positive correlations with T helper cells, central memory T cells, macrophages, and Th2 cells. The expression of ZNF132 was significantly associated with clinical pathological features in colorectal cancer patients, including age, M stage, and pathological grade. ROC curve analysis indicated that ZNF132 possesses high sensitivity and specificity for colorectal cancer diagnosis (AUC = 0.845). Kaplan-Meier analysis further confirmed that elevated ZNF132 expression correlates with extended survival in colorectal cancer patients. Multivariable Cox regression analysis identified ZNF132 as an independent risk factor for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in these patients. Enrichment analysis suggested that ZNF132 modulates tumor progression by influencing calcium signaling, PPAR pathways, and apoptosis-related genes. Functional assays demonstrated that ZNF132 significantly inhibits the proliferation, migration, and invasion of colorectal cancer cells. Conclusion: ZNF132 functions as a novel tumor suppressor, influencing colorectal cancer progression through the regulation of the immune microenvironment and malignant cellular phenotypes. Its diagnostic and prognostic potential offers new therapeutic targets for clinical application.