Sex Dimorphism in DEN/TCPOBOP-Induced Hepatocellular Carcinoma

Background

Hepatocellular carcinoma (HCC) is markedly more common in males, but the mechanism behind that sex bias is not well resolved — particularly which molecular differences appear at which stage of disease progression, and whether they are causes or consequences.

Method

Using a DEN/TCPOBOP-induced mouse model, I analysed paired transcriptomic and metabolomic data across 174 mice, spanning three stages of progression: hepatitis, cirrhosis, and HCC.

The analysis had three parts:

1. Multi-omics profiling to identify metabolites that differ by sex across stages.
2. A hormone rescue arm, testing whether estrogen supplementation moves those markers.
3. Network integration, linking WGCNA and PPI hub genes back to the metabolomic findings.

Tools: R (DESeq2, WGCNA), Python, transcriptomics, metabolomics.

Results

• 12 core sex-biased metabolites were identified, concentrated in the bile acid, tryptophan, and acylcarnitine pathways.
• Estrogen supplementation reversed the bile acid marker TUDCA (+97%) and rescued roughly half of the male–female gap in a composite disease score.
• 155 links between hub genes and metabolomic findings emerged from network integration, pointing to candidate drivers of sex-biased liver disease progression.

The project is ongoing.