The Oncogenic and Immunological Roles of Apoptosis Antagonistic Transcription Factors in Human Tumors: A Pan-Cancer Analysis

Abstract

Background. Apoptosis-antagonizing transcription factor (AATF) participates in tumor progression in multiple cancer types. However, its role across cancers is not well understood. Methods. Data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) were used to analyze the multiomic roles of AATF in 33 tumor types, including gene and protein expression, survival prognosis, gene mutation, DNA methylation, protein phosphorylation, AATF coexpressed genes and their enrichment analysis, and immunological analysis. Results. In TCGA and GTEx databases, 31 tumors and their corresponding normal tissues had AATF expression data, and it was differentially expressed in 29 of them. AATF was elevated in 27 tumors, decreased in 2 tumors, and was a risk factor for overall survival (OS) in 8 tumors and a risk factor for disease-free survival (DFS) in 4 tumors. AATF expression levels in various cancer types were significantly correlated with the infiltration levels of cancer-associated fibroblasts, endothelial cells, CD4+ T cells, B cells, myeloid dendritic cells, eosinophils, and macrophages. The immune checkpoints PD-1, PD-L1, and CTLA4 were positively correlated with AATF expression in bladder urothelial carcinoma (BLCA), kidney chromophobe (KICH), and prostate adenocarcinoma (PRAD). Conclusion. In cancer, AATF expression is generally higher than that in normal tissue, and it is also associated with immunomodulation-related genes. AATF may be a risk factor for poor prognosis across cancers.