Abstract 5758: Characteristic profile of blood-based ctDNA suggests angiogenesis and immune escape in hepatocellular carcinoma

Abstract Background: Circulating tumor DNA (ctDNA) is a type of DNA released from tumor cells captured in blood circulation system. It provides a noninvasive approach to interrogate a patient’s genomic landscape and actionable mutations with well application prospect. However, the difference of genomic profiles between tissue and ctDNA still brings confusions to related researches. Therefore, we tried to elucidate whether blood-based ctDNA has its own characteristic profile to reflect tumor status in hepatocellular carcinoma (HCC). Methods: Tumor tissue and blood samples from 118 HCC patients of Xiangya Hospital Central South University, were analyzed using NGS (panel on 147 gene). NGS data from a Chinese population extended cohort (385 tissues and 79 blood samples) of HCC were used to validate the mutation characteristics. Data from HCC cohorts of The Cancer Genome Atlas (TCGA) was used to analyze the disease-free survival (DFS) of different mutations. Results: In the hospital cohort, there were 9 high-frequency mutant genes in tissue and blood, including TP53 (74.58% vs 74.58%), MSH2(23.73% vs 8.47%), LRP1B (20.34% vs 23.73%), ATM (18.64% vs 13.56%), CTNNB1 (11.86% vs 13.56%) et.al which consistent with previous reports. There were 32 genes (74.04%) with a mutation frequency of more than 6% that were unique to blood samples. In extended cohort, the mutation profile was similar to the hospital cohort, in which 35 genes (52.24%) specific in ctDNA profile and 18 genes of them identical to the hospital cohort. Interestingly, when these ctDNA-specific genes were analysed by gene ontology, most genes were involved in angiogenesis. The prognostic analysis in ctDNA-specific genes showed that patients with higher level of MAP3K1 had worse DFS (p=0.028). In addition, the gene co-expression network analysis showed MAP3K1 and NOTCH1/2/3 expression had a significant positive correlation, that Notch family members were also belonged to the ctDNA-specific genes and associated with tumor immune escape. Conclusions: The results showed the mutation characteristic of tissues and ctDNA in HCC, and suggest that angiogenic and tumor immune escape related ctDNA-specific genes might be able to predict recurrence risk independently of baseline tissue samples. Citation Format: Lin Chia Yan, Liu Miao, Hu Xue, Huang Meng Li. Characteristic profile of blood-based ctDNA suggests angiogenesis and immune escape in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5758.