Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Karyopherin alpha2 (KPNA2) dysregulation is implicated in various cancers, including hepatocellular carcinoma (HCC).
• A comprehensive multi-omics understanding of KPNA2 in HCC is crucial for advancing diagnostic, prognostic, and therapeutic strategies.

Purpose of the Study:

• To conduct a multi-omics analysis of KPNA2 alterations in HCC at genetic, epigenetic, transcriptomic, and proteomic levels.
• To investigate the correlations between KPNA2's molecular characteristics and HCC's clinicopathological features.
• To develop predictive models for HCC patient survival and explore KPNA2's role in immune infiltration and metabolic pathways.

Main Methods:

• Integrative multi-omics analyses including gene copy number variation (CNV), methylation, and gene expression.
• Statistical analyses such as Spearman correlation, Cox regression, Kaplan-Meier survival, and receiver operating characteristic (ROC) analyses.
• Evaluation of immune cell infiltration using Microenvironment Cell Populations-counter (MCP-counter) and assessment of KPNA2 protein levels via ELISA.

Main Results:

• Significant correlations were found between KPNA2 expression, its CNV, and methylation status in HCC.
• Constructed risk models based on KPNA2 alterations and tumor stage effectively predicted overall survival (OS) and disease-free survival (DFS).
• KPNA2 expression showed associations with immune cell infiltration and fatty acid metabolism pathways, and was decreased in HCC patient plasma.

Conclusions:

• Multilevel dysregulation of KPNA2 in HCC is linked to immune infiltration and fatty acid metabolism.
• KPNA2 exhibits significant clinicopathological relevance in HCC, highlighting its potential as a diagnostic and prognostic biomarker.
• The study underscores KPNA2's multifaceted roles in HCC progression and suggests its potential as a therapeutic target.