Low expression of BAZ2B may promote breast cancer progression by reshaping tumour metabolism, suppressing apoptosis and altering immune signalling, according to a comprehensive multi-omics analysis combining patient datasets with laboratory experiments.
BAZ2B (bromodomain adjacent to zinc finger domain 2B) is a chromatin-associated protein involved in epigenetic regulation, non-coding RNA control and ageing. While its biological functions are increasingly recognised, its relevance in cancer has been uncertain. New data suggest BAZ2B acts as a tumour suppressor in breast cancer and potentially across multiple malignancies.
BAZ2B Expression Linked to Prognosis and Diagnosis
Using large public datasets including TCGA, GEO and GTEx, researchers found that BAZ2B expression was consistently reduced in several cancer types, with particularly marked downregulation in breast cancer. Lower BAZ2B levels were associated with poorer overall survival on Kaplan–Meier analysis, suggesting prognostic significance.
Receiver operating characteristic analyses also indicated diagnostic potential, as BAZ2B expression reliably distinguished tumour tissue from normal breast tissue. Immune profiling using TIMER2.0 showed correlations between low BAZ2B expression and altered immune cell infiltration, hinting at broader effects on the tumour microenvironment.
Functional Impact on Tumour Behaviour
Laboratory experiments helped translate these bioinformatic findings into clinically meaningful biology. Knocking down BAZ2B in breast cancer cell lines led to increased proliferation, colony formation, migration and invasion, while apoptosis was suppressed.
At a molecular level, BAZ2B depletion reduced pro-apoptotic proteins Bax and p53, alongside increased expression of the anti-apoptotic protein Bcl-2. These changes align with a more aggressive, treatment-resistant phenotype that clinicians often encounter in advanced disease.
Metabolic Reprogramming and Signalling Pathways
Loss of BAZ2B also promoted glycolytic metabolism, a hallmark of cancer progression. Cells with reduced BAZ2B showed increased lactate production and upregulation of key glycolytic enzymes including LDHA, HK1, HK2, PKM2 and PFK1. This supports a role for BAZ2B in restraining the Warburg effect.
Integrated multi-omics analyses further revealed co-activation of pro-inflammatory signalling and mTOR pathways, alongside suppression of apoptotic mechanisms and disruption of DNA repair processes.
Clinical Implications for Breast Cancer Care
Validation using tissue microarrays, proteomic data and immunohistochemistry confirmed reduced BAZ2B expression in tumour samples compared with adjacent normal tissue. While causality cannot yet be assumed, these findings position BAZ2B as a promising biomarker and potential therapeutic target. Further studies will be needed to determine whether restoring BAZ2B activity could translate into clinical benefit for patients with breast cancer.
Reference
Guo J et al. Pan-cancer and multi-omics analyses reveal the diagnostic and prognostic value of BAZ2B in cancer. Scientific Reports. 2026; doi: 10.1038/s41598-025-33622-2.
