School of Law and Criminal Justice, East China University of Political Science and Law, No. 555 Longyuan Road, Songjiang University Town, Shanghai 201620, China.
Shanghai Institute of Blood Transfusion, Shanghai Blood Center, No. 1191 Hongqiao Road, Shanghai 200051, China.
Biomolecules. 2022 Jun 13;12(6):822. doi: 10.3390/biom12060822.
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.
PBX4 属于前 B 细胞白血病同源盒 (PBX) 转录因子家族，作为 HOX 蛋白的转录共因子发挥作用，参与多种病理生理过程。最近的研究表明，PBX4 的失调与多种疾病密切相关，尤其是癌症。然而，来自癌症基因组图谱 (TCGA) 的 33 种癌症中 PBX4 潜在作用的研究仍然不足。因此，我们使用多个公共数据库进行了全面的泛癌症分析，以探索 PBX4 的作用。我们的结果表明，PBX4 在 17 种人类癌症中表达差异，并与病理分期、肿瘤分级以及免疫和分子亚型显著相关。我们使用 Kaplan-Meier plotter 和 PrognoScan 数据库发现 PBX4 表达与多种癌症预后值之间的显著关联。还发现 PBX4 表达与突变状态、DNA 甲基化、免疫浸润、药物敏感性和免疫检查点阻断 (ICB) 治疗有统计学上的关联。此外，我们从单细胞分辨率的角度发现 PBX4 参与了多种癌症的不同功能状态。富集分析结果表明，PBX4 相关基因富集在细胞周期过程、MAPK 级联、ncRNA 代谢过程、GTPase 活性的正调控以及脂肪酶活性的调节等过程中，主要参与胆固醇代谢、碱基切除修复、单纯疱疹病毒 1 感染、癌症转录失调和 Epstein-Barr 病毒感染等途径。总之，我们的综合分析可以帮助更好地理解 PBX4 在不同人类癌症中的潜在作用。
