An Integrative Analysis Reveals the Underlying Association Between CTNNB1 Mutation and Immunotherapy in Hepatocellular Carcinoma

Abstract

Background: Tumor mutational burden (TMB) was verified to be closely associated with immune checkpoint inhibitors, but it is unclear whether gene mutation has an effect on immunotherapy of hepatocellular carcinoma (HCC). This research aimed to investigate the underlying correlation between gene mutation and immunotherapy in HCC. Methods: The somatic gene mutation data and gene expression data were retrieved from International Cancer Genome Consortium database and The Cancer Genome Atlas (TCGA) database. The mutational genes were selected by the intersection of three cohorts and further identified using survival analysis and TMB correlation analysis. After the identification of key mutational gene, we explored the correlation between gene mutation and both the immune cell infiltration and immune inhibitors. The signaling pathways associated with gene mutation were confirmed through gene set enrichment analysis. Furthermore, the survival analysis and mutational analysis based on TCGA cohort were performed for the validation of included gene. Conclusion: Our research firstly revealed the underlying association between CTNNB1 mutation and immunotherapy, and we speculated that CTNNB1 mutation may modulate NK cells by affecting CD96. However, more functional experiments should be performed for verification.

Multiomics analysis of tumor mutational burden across cancer types

“…In combination with the aforementioned findings, we attributed the poor prognosis of KICH patients with a high TMB to the higher frequency of TP53 mutations ( Table S1 A). In patients with LIHC, we found that the CTNNB1 mutation group had a higher TMB ( Table S1 A), which was significantly correlated with a better prognosis in LIHC [65] . The TMB of the TP53 mutation group was also higher ( Table S1 A), which has previously been reported to be related to a higher TMB and worse outcome in patients with hepatocellular carcinoma [66] .…”

Strong ALK and PD-L1 positive IHC expression related ALK amplification in an advanced lung sarcomatoid carcinoma: A therapeutic trap?

“…The presence of the CTNNB1 mutation has also been associated with a better response to immunotherapy in other cancers. [16,17] This could be explained by the role of CTNNB1 in modulating the activity of NK cells by affecting CD96. Further investigations should be performed to better understand the role of this mutation in non-small cell lung cancer.…”

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

“…Therefore, it can be considered as a reliable biomarker for HCC response to immunotherapy. 77 Next generation sequencing (NGS) seems to be beneficial in clinical course and for treatment of HCC patients, as it can provide predictions about advantages of immunotherapy in HCC patients. The mutation in CTNNB1 and abnormal activation of Wnt/β-catenin signaling reduce response of HCC patients to immune checkpoint inhibitors.…”