The association between bromodomain proteins and cancer stemness in different solid tumor types

Area of Science:

• Oncology
• Epigenetics
• Molecular Biology

Background:

• Cancer stemness, characterized by stem cell-like traits, drives tumor development and relapse.
• Epigenetic aberrations, including bromodomain (BrD) proteins, are implicated in cancer, but their role in cancer stemness is unclear.

Purpose of the Study:

• To investigate the association between bromodomain protein expression and cancer stemness across various solid tumors.
• To identify specific BrD proteins linked to cancer stemness and explore their therapeutic potential.

Main Methods:

• Utilized TCGA and GEO databases for gene expression analysis.
• Employed bioinformatic tools including Oncomine, PrognoScan, GEPIA2, TIMER2.0, TISIDB, GSEA, and R2 platform.
• Correlated BrD family member expression with cancer stemness markers and tumor grade.

Main Results:

• Upregulation of ATAD2 and SMARCA4, and downregulation of SMARCA2, were associated with enhanced cancer stemness.
• High ATAD2 expression, particularly in higher-grade tumors, correlated with stem cell markers and c-Myc targets.
• The association of other BrD proteins with de-differentiation was tumor-specific.

Conclusions:

• Bromodomain proteins, especially ATAD2, play a significant role in regulating cancer stemness across diverse solid tumors.
• High ATAD2 expression is a robust indicator of cancer stemness and MYC pathway activation.
• ATAD2 represents a promising druggable target for treating de-differentiated tumors, particularly those with MYC overexpression.