Abstract 1012P
Background
Immune checkpoint inhibitors (ICI) therapy is not suitable for all patients with cancer, and hepatocellular carcinoma (HCC) included, it depend largely on characteristics of tumor and biomarkers, We analyzed features of HCC related to biomarkers of immunotherapy such as tumor mutation burden (TMB), PD-L1 expression, and gene landscape, and mainly focused on the tumor location.
Methods
Tumor samples of 173 HCC patients were consecutively collected in China from January 2018 to November 2019, gene mutation and TMB level were analyzed by next generation sequencing (NGS), detected PD-L1 expression by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. TPS was arranged into the following intervals: strong positive ≥50%, moderate positive ≥5% and <50%, weak positive ≥1% and <5%, and negative <1%.
Results
All these tissue samples were divided as right (n=118) and left (55) hepatic lobe according anatomical location, NGS analysis showed that, higher mutation frequency of several genes, such as CTNNB1 (22.0% Vs 10.9%), CCND1 (6.8% Vs 1.8%), KEAP1 (10.2% Vs 1.8%), SMAD4 (5.1% Vs 1.8%) were found in right than in left hepatic lobe (p<0.05); while several other gene such as ARID1A (23.6% Vs 13.6%), ARID2 (14.5% Vs 5.1%), ALB (12.7% Vs 1.7%), were mutated more frequently in left than right hepatic lobe (p<0.05). TMB level was significantly different in right and left hepatic lobe (p<0.05), the media TMB level was 7.13 and 4.3 mutations/Mb for right and left hepatic lobe, respectively. Among these 173 HCC patients, 104 were detectable for PD-L1 expression. 32% (24/74) of right hepatic lobe were PD-L1 positive, 27% (8/30) of left were PD-L1 positive. Percentage of individuals had TPS as strong positive (2.7% Vs 0) and moderate positive (1.3% Vs 6.7%) were different between right and left hepatic lobe, while no significant difference was found for percentage of individuals had TPS as weak positive and negative.
Conclusions
Different anatomical sites of liver cancer hold different gene landscape, level of TMB and PD-L1 expression, this suggest HCC patients with different tumor location should be treated differently in the clinic, especially, for using immune checkpoint inhibitors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Zhang: Full/Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.