Transcriptomic characterization of hepatocellular carcinoma with CTNNB1 mutation

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Hepatocellular carcinoma (HCC) is a prevalent cancer globally and a significant health concern in China.
• Understanding the genetic landscape of HCC is crucial for developing effective treatments, especially in specific populations.

Purpose of the Study:

• To systematically analyze somatic mutations in Chinese HCC patients.
• To investigate the molecular mechanisms underlying HCC tumorigenesis in this population.
• To identify potential therapeutic targets for Chinese HCC patients.

Main Methods:

• Genotyping of hotspot mutations in key cancer-related genes (CSF1R, CTNNB1, KRAS, BRAF, NRAS, ERBB2, MET, PIK3CA, JAK1, SMO) in 156 HCC samples (110 HBV-positive, 46 HBV-negative).
• Transcriptomic analysis of CTNNB1 mutation-positive HBV-positive (CB+ HCC) tumors compared to adjacent non-cancerous liver tissue.
• In vitro functional validation of significantly altered genes.

Main Results:

• CTNNB1 mutations were the most frequent genetic alterations found.
• A slightly higher mutation rate was observed in HBV-positive HCC patients.
• Distinct CTNNB1 mutation patterns were identified between HBV-positive and HBV-negative groups.
• Significant transcriptomic changes were observed in CB+ tumors.
• Potential tumor suppressors (FoxA3, Onecut1) and oncogenes (MAFG, SSX1) were functionally validated.

Conclusions:

• This study provides the first comprehensive characterization of oncogenic mutations in Chinese HCC.
• Targeting the Wnt-β-catenin pathway is a potential therapeutic strategy for Chinese HCC patients.
• Targeting specific genes (ONECUT1, FOXA3, SSX1, MAFG) may be beneficial for CTNNB1 mutation-positive HCC.