ZNF556 serves as an immunological and prognostic biomarker in colon adenocacinoma

Colon adenocarcinoma (COAD) is one of the most common and deadliest digestive tract malignancies, but its diagnostic and prognostic markers still need further exploration as targets for risk stratification and treatment response.

COAD cohorts were retrieved from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Differences in gene expression were analyzed using relevant R packages, followed by gene function enrichment analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Next, the Kaplan-Meier method and LASSO regression analysis were employed to screen for prognostic signature genes associated with the survival of COAD patients. Furthermore, comprehensive analyses were conducted to assess the role of this signature gene in immunomodulation and genetic mutation. Single-cell RNA sequencing (scRNA-seq) analyses were performed using the GSE166555 dataset. Additionally, CCK-8, colony formation, wound healing and Transwell assays were used to evaluate the biological functions of the signature gene in COAD cells.

Differential expression analysis and WGCNA led to the identification of 156 candidate genes, which were primarily enriched in functional pathways including the cell cycle, P53 signaling pathway, and cellular senescence. Subsequently, LASSO regression combined with survival analysis screened out ZNF556 as a characteristic prognostic gene for COAD. The expression level of ZNF556 correlates with the infiltration of plasma cells, mast cells, and monocytes, and is further associated with the expression of multiple immune checkpoint genes. Additionally, gene mutation analysis revealed a significant correlation between mutant TP53 and ZNF556 expression. ScRNA-seq analysis further indicated that, in the context of COAD, ZNF556 may exert a key regulatory role in the differentiation of epithelial cells, thereby facilitating tumor initiation and progression. Furthermore, subsequent experiments confirmed the cancer-promoting effect of ZNF556, whose expression was positively regulated by mutant TP53.

ZNF556 was highly up-regulated in COAD tissues, with high expression correlating with poor prognosis and difference in TIICs. It functions as a diagnostic, immunological and prognostic biomarker for COAD, and a potential therapeutic target.