Abstract 1457: Discovery of biomarkers assocaited with treatment responses to sorafenib and transarterial chemoembolisation (TACE) in Chinese hepatocellular carcinoma patients

Abstract

Abstract Background: Liver cancer is one of the most deadly tumors. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. Sorafenib, a multi-target kinase inhibitor, is one the main systemic therapy drug of HCC. It increased the median overall survival time from 7.9 mo to 10.7 mo for patients with advanced stage HCC. However, about 60% of HCC patients done't respond well to sorafenib, and most of them develop progression in below 6 mo. Similarly, TACE is also an effective treatment of HCC but only with partial response rate. Therefore, finding new strategies to screen the best matched patients is key to improve the efficacy of sorafenib and TACE treatment. Methods: We evaluated the efficacy of sorafenib starting with 98 HCC patients but only 73 patients completed the study because 24 dropped out due to death (n=2), drug violation (n=4), adverse reactions (n=3), and failure of outcome evaluation (n=15). Forty-five patients were treated by TACE. We divided the patients to a progressive disease (PD) group (46.6%, 34 patients) and a Non-PD group (53.4%, including 2 with partial response and 37 with stable disease) based on their CT and MRI evaluations. At the same time, we performed Whole-exome sequencing (WES) on the tumor samples and patient-matched blood samples. Results: We found the PD group, comparing with the Non-PD group, had a higher proportion of patients with MSI (P = 0.028) and mutations in WNT/ß-catenin signaling and chromatin modification pathways, as well as cytoband deletions at 21q11, 1p21.1, 8q24.3, 11p11.12, 5p15.33, and 17q25.3. On contrast, cytoband amplifications at 12p13, 21q22.3, and 8q21 only appeared in the Non-PD group. We also observed a prominent decrease in the PD group COSMIC mutational signature 10 which is believed to associate with POLE mutation. We found MUC16 and FLG2 genes were related to a better survival time. Mutation of NANOGNB, and cytoband deletions at 3q11.2, 4q13.2,11q11,11q22.2 and 17q25.3 were related to a shorter survival time. (p<0.05 for all above except otherwise specified). Conclusions: We found several genes and chromosome variation were associated with sorafenib efficacy and overall survival in HCC patients. These findings indicated that mutations and chromosomal fragment deletions can lead to sorafenib resistance. Mutations of MUC16 and FLG2 may be potential drug targets in HCC. Citation Format: Zhiqiang Wu, Xiaoyu Zhou, Shengzhou Wang, Jinhuai Li, Jun Liu, Wenbo Guo. Discovery of biomarkers assocaited with treatment responses to sorafenib and transarterial chemoembolisation (TACE) in Chinese hepatocellular carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1457.