Abstract 995P
Background
CTNNB1, encoding β-catenin and associated with regulation of WNT pathway, plays an important role in development of hepatocellular carcinoma (HCC). It was reported as an immune-resistant biomarker in HCC. However, the landscape of CTNNB1 mutations in Chinese HCC patients and mechanisms of CTNNB1 mutations underlying immune resistance remain unclear.
Methods
FFPE tumor and matched blood samples of 1303 Chinese HCC patients were analyzed in a CAP & CLIA certified laboratory using next-generation sequencing targeting 450 cancer genes. IHC staining was performed on FFPE tissue sections of 672 HCC patients using anti-PD-L1 antibody 28-8 or 22C3. A total of 408 HCC patients from public database were also included to evaluate the relationship between CTNNB1 mutations and tumor infiltrating lymphocytes (TILs). Mutational data was collected from TCGA and immune cell infiltration data was downloaded from TIEMR website.
Results
CTNNB1 mutations were detected in 20.2% of Chinese HCC patients, and 98.5% mutations were SNV/Indels. D32-S37 within the β-TRCP binding site was hot-spot region (55.0%). Compared with wild-type cohort, mutational frequencies of ARID2 (10.3% vs. 4.9%, P<0.01) and NFE2L2 (7.6% vs. 3.3%, P<0.01) were significantly higher in patients with CTNNB1 mutations, whereas TP53 (44.5% vs. 64.7%, P<0.01), RB1 (1.9% vs. 16.2%, P<0.01), AXIN1 (6.1% vs. 14.7%, P<0.01) mutations and 11q13 amplification (4.6% vs. 10.4%, P<0.01) were less abundant. CTNNB1 mutations were found to be significantly correlated with TMB-H (top 20% of HCC, 29.7% vs. 20.4%, P<0.01), but not correlated with PD-L1 expression (CPS>1). TILs analysis revealed that CD4+, CD8+ T cells, dendritic cells, macrophages and neutrophils infiltration were significantly lower in CTNNB1-mutant HCC patients (P<0.01 for all).
Conclusions
This is the largest Chinese HCC cohort studying the variation information of CTNNB1 and CTNNB1 mutations occurred in 20.2% of patients. CTNNB1 mutations were significant associated with TMB-H but showed lower immune cell infiltration in HCC patients. Further researches are still needed to better understand the most appropriate treatments for CTNNB1-mutant HCC population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.