YBX1 Expression Marks Proliferative Tumour States with Context-Dependent Genomic Instability: A Pan-Cancer Analysis

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Y-box binding protein 1 (YB-1) is a DNA/RNA-binding protein involved in cell cycle regulation, DNA repair, and stress adaptation.
• Elevated YB-1 expression is linked to aggressive cancers, but its pan-cancer genomic and clinical associations require further definition.

Purpose of the Study:

• To investigate the pan-cancer genomic and clinical correlates of YBX1 expression.
• To determine if YBX1's association with genomic instability reflects proliferative activity or an independent program.

Main Methods:

• Integrative pan-cancer analysis of transcriptomic, proteomic, genomic, and clinical data across 53 datasets (33 tumor types).
• Analysis of YBX1 mRNA and YB-1 protein levels.
• Correlation of YBX1 expression with mutation burden, chromosomal alterations, hypoxia, and homologous recombination deficiency.

Main Results:

• YBX1 mRNA expression is highly variable, rarely altered at the genomic level.
• High YBX1 expression correlates with cell cycle, mitotic, and signaling pathways, and aggressive clinicopathological features.
• YBX1 expression associates with increased mutation burden, chromosomal alterations, and hypoxia, but the latter is attenuated by accounting for proliferation.
• High YBX1 mRNA and protein levels are linked to advanced disease stage, higher grade, and poorer survival.

Conclusions:

• Elevated YBX1 expression identifies proliferative and aggressive tumor states.
• Genomic instability features associated with YBX1 likely arise from shared proliferative biology.
• YB-1 serves as a pan-cancer biomarker for aggressive disease and poor prognosis.