Investigating the Prognostic Potential of ABTB1 Identified as a Hub Gene in B-Cell Acute Leukemia through Bioinformatics Analysis

Abstract

Background: Although some studies have highlighted the potential tumor-suppressive role of Ankyrin repeat and BTB/POZ domain-containing protein 1 (ABTB1) in various malignancies, its significance in B-cell acute lymphoblastic leukemia (B-ALL) remains unclear. This study aimed to explore the potential of ABTB1 as a prognostic marker for B-ALL. Methods: Firstly, we identified differentially expressed genes (DEGs) in a patient with recurrent B-ALL, encompassing recurrence and complete remission, using bioinformatics methods. A protein-protein interaction (PPI) network for the identified DEGs was constructed using the Search Tool for Recurring Instances of Neighbouring Genes (STRING) database and visualized using Cytoscape software. Hub gene analysis was conducted utilizing three distinct algorithms (Degree, Maximal Clique Centrality (MCC), and Density of Maximum Neighborhood Component (DMNC)) via the cytoHubba plugin. The top 15 genes identified by each algorithm were designated as hub genes. Subsequently, transcriptome and clinical data from the TARGET database were then retrieved. mRNA expression profiles from 199 B-ALL cases were subjected to univariate Cox analysis to identify prognostic gene markers. Hub genes (p < 0.05) were then isolated from this gene pool. Kaplan-Meier analysis was conducted to examine the association between the extracted hub genes and overall survival (OS). Further screening of OS-related hub genes, considering hazard ratios from univariate Cox analysis and the regulatory patterns of DEGs, identified potential prognostic biomarkers. Finally, the expressions of the screened hub genes were validated, and their clinical significance was assessed in paediatric B-ALL patients. Results: A total of 2666 DEGs were identified, comprising 930 upregulated and 1736 downregulated genes. Three candidate hub genes, namely ABTB1 (Hazard Ratio (HR) = 0.683, p < 0.05), a disintegrin and a metalloproteinase domain-8 (ADAM8) (HR = 0.729, p < 0.05), and G protein-coupled 84 (GPR84) (HR = 0.868, p < 0.05), were markedly downregulated and associated with poor prognosis in B-ALL. Subsequent validation revealed that only ABTB1 was differentially expressed between newly diagnosed B-ALL patients and those with complete remission. Furthermore, ABTB1 exhibited significant associations with white blood cell count and risk stratification. Additionally, the protein expression of ABTB1 was reduced in newly diagnosed B-ALL patients. Conclusions: ABTB1 emerges as a promising novel prognostic biomarker in B-ALL, shedding light on its potential role in disease progression and prognosis.