Abstract
OBJECTIVE: The PYGO2 gene plays a significant role in various cancers. However, its prognostic significance and involvement in immune infiltration in liver cancer remain unclear. This study aimed to comprehensively evaluate PYGO2 expression and its associations with prognosis and clinicopathological features in liver cancer. METHODS: Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were analyzed. Functional enrichment analysis and immune cell infiltration assessments were performed to explore potential pathogenic mechanisms. RESULTS: PYGO2 was highly expressed in multiple cancer types, including bladder urothelial carcinoma, breast invasive carcinoma, cholangiocarcinoma, diffuse large B-cell lymphoma, and liver cancer. Analysis of 50 paired liver cancer tissues from TCGA revealed significant upregulation of PYGO2 expression. Moreover, high PYGO2 expression was significantly associated with pathological T stage, overall pathological stage, tumor status, and race. Kaplan-Meier survival analysis showed that low PYGO2 expression correlated with improved overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in liver cancer patients. Functional enrichment analysis identified several enriched pathways, including the reactive oxygen species signaling pathway, MYC targets, interferon-alpha response, immune response regulation signaling pathway, and leukocyte migration. Additionally, PYGO2 overexpression was associated with lower proportions of cytotoxic cells, dendritic cells, immature dendritic cells, mast cells, neutrophils, plasmacytoid dendritic cell-like cells, Th17 cells, and regulatory T cells, but a higher proportion of Th2 cells. Furthermore, the high PYGO2 expression group exhibited increased immune checkpoint gene expression, particularly PDCD1. CONCLUSION: PYGO2 is a promising prognostic biomarker for liver cancer, given its strong associations with clinicopathological features, survival outcomes, and immune-related characteristics.