CTNNB1 mutations in hepatocellular carcinoma: Prognostic significance and superior survival outcomes in patients treated with immunotherapy

Background: Hepatocellular Carcinoma (HCC) is a fatal malignancy which carries variable responses to standard treatments. Recent advances in genetic research have provided a clearer image of some mutations driving HCC development, which gave an opportunity for targeted therapies like (Wnt/B-catenin) pathway inhibitors to intervene. CTNNB1 (B-catenin) gene mutation, which is present in 20-40 was found to affect behavior of the tumor and its response to treatment and was linked with a better overall prognosis and may be a therapeutic target for HCC treatment. We aim to further investigate the impact of CTNNB1 mutations on treatment response and overall survival (OS) in patients with HCC. Methods: We used cBioPortal for Cancer Genomics server to gather data of 2453 samples from 5 studies conducted between 2018 and 2024. The data were used to analyze the prevalence of CTNNB1 mutation in HCC patients, its impact on survival rates, and how it compares to other common mutations like TP53. Survival outcomes for HCC patients who received immunotherapy as part of their treatment regimen were compared between CTNNB1 and TP53 mutations. Kaplan-Meier survival curves were generated for median OS analysis and compared by using log-rank test. All statistical comparisons were considered significant if p lt; 0.05. Results: Our study cohort included patients with HCC who received immunotherapy as part of their treatment. Males constituted 64.2 while the remainder were females. More than half of our study subjects were white constituting about 55.73 and CCTNNB1 mutations was 540 and 174, respectively. Patients with TP53 mutation had a median OS of 25.15 months (95 22.61 - 28.15) compared to 39.78 months (95 32.56 - 53.33) among CTNNB1 patients. The difference was statistically significant (p=0.00314). Conclusion: Our study suggests that CTNNB1 mutations in HCC are linked to a better median OS compared to TP53 mutations, which aligns with current literature data. This also suggests that therapies targeting the Wnt/B-catenin pathway may represent promising therapeutic outcomes for HCC patients. However, further research is crucial to validate these findings and assess the clinical implications of CTNNB1 mutation status to provide personalized treatment plans and ultimately improve patient care.Citation Format: Bayan Khasawneh, Saifudeen Abdelrahim, Abdullah Esamil, Ebtesam Al-Najjar, Maen Abdelrahim. CTNNB1 mutations in hepatocellular carcinoma: Prognostic significance and superior survival outcomes in patients treated with immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A037.