Comprehensive Analysis of Biologic and Prognostic Implication for ZNF536 in Pan-Cancer

Objectives: Zinc Finger Protein 536 (ZNF536) is a highly conserved zinc finger protein, acting as DNA-binding transcrip-tion suppressor, and negatively regulating neuron differentiation. However, the role of ZNF536 in cancers is still unknown. Methods: In this study, we aim to comprehensively explore the biologic and prognostic implication of ZNF536 in pan-cancer by multi-layered analysis. The mRNA differential expression and DNA methylation of ZNF536 in pan-cancer and normal controls based on The Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEx) data were inter-preted. Immunohistochemistry was performed on a tissue micro-array to detect the protein expression of ZNF536. The prognostic implication of ZNF536 in pan-cancer was studied by survival analysis. The cBioPortal database was used to display ZNF536 genomic alterations. The co-expression of ZNF536 and immune-related genes in pan-cancer was inves-tigated. Further research was made on the relationship between ZNF536 expression and tumor immune microenviron-ment. CancerSEA was employed to excavate the ZNF536 expression at single cell level with different cancer function. The biological function of ZNF536 in pan-cancer was exhibited by gene enrichment analysis. Results:The ZNF536 mRNA was highly expressed in 4 out of 33 cancers, but lowly expressed in 22 cancers. Immunohis-tochemistry on the tissue micro-array confirmed the high expression of ZNF536 protein in pancreatic adenocarcinoma (PAAD) and low expression in stomach adenocarcinoma (STAD). DNA hypermethylation in prostate adenocarcinoma (PRAD) was observed, which might result in its down-regulated expression. High expression of ZNF536 predicted poor prognosis in 5 cancers, but predicted favorable prognosis in 2 cancers. Genomic alterations of ZNF536 showed mu-tation in 26 cancers and amplification in 20 cancers. The altered group usually had worse prognosis. ZNF536 mRNA expression was correlated with the degree of immune infiltrates in pan-cancer. Single cell sequencing and gene enrich-ment analysis showed that the ZNF536-correlated genes might regulate a variety of biological processes in pan-cancer, mainly via angiogenesis pathway. Conclusion: Our results indicated that ZNF536 might be a prognostic and immune-related biomarker for specific ma-lignancies through the angiogenesis pathway.