Identifying the Potential Roles of PBX4 in Human Cancers Based on Integrative Analysis

Abstract

PBX4 belongs to the pre-B-cell leukemia homeobox (PBX) transcription factors family and acts as a transcriptional cofactor of HOX proteins participating in several pathophysiological processes. Recent studies have revealed that the dysregulation of PBX4 is closely related to multiple diseases, especially cancers. However, the research on PBX4’s potential roles in 33 cancers from the Cancer Genome Atlas (TCGA) is still insufficient. Therefore, we performed a comprehensive pan-cancer analysis to explore the roles of PBX4with multiple public databases. Our results showed that PBX4 was differentially expressed in 17 types of human cancer and significantly correlated to the pathological stage, tumor grade, and immune and molecular subtypes. We used the Kaplan–Meier plotter and PrognoScan databases to find the significant associations between PBX4 expression and prognostic values of multiple cancers. It was also found that PBX4 expression was statistically related to mutation status, DNA methylation, immune infiltration, drug sensitivity, and immune checkpoint blockade (ICB) therapy. Additionally, we found that PBX4 was involved in different functional states of multiple cancers from the single-cell resolution perspective. Enrichment analysis results showed that PBX4-related genes were enriched in the cell cycle process, MAPK cascade, ncRNA metabolic process, positive regulation of GTPase activity, and regulation of lipase activity and mainly participated in the pathways of cholesterol metabolism, base excision repair, herpes simplex virus 1 infection, transcriptional misregulation in cancer, and Epstein–Barr virus infection. Altogether, our integrative analysis could help in better understanding the potential roles of PBX4 in different human cancers.