The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody

BACKGROUND: Based on molecular biomarkers, anti-angiogenic drugs in combination with programmed cell death protein 1 (PD-1) antibodies can screen the potentially beneficial populations with hepatocellular carcinoma (HCC) and predict the efficacy after treatment. Therefore, we aimed to study predictive molecular biomarkers to improve the effectiveness of immuno-targeted combination therapy for HCC. PATIENTS AND METHODS: Baseline clinical data, blood samples, and imaging data of the first evaluation after two cycles of treatment were collected for 40 patients with advanced HCC who underwent combination therapy, and then these data were compared according to the efficacy. Since 15 patients had complete hematology samples, we additionally tested the T lymphocyte subpopulations of these 15 patients and also compared them according to the efficacy. In addition, we also selected five patients who benefited the most from the combination therapy and five patients with the worst curative effect for gene detection based on survival time and efficacy evaluation. Finally, the relationship between certain clinical characteristics, laboratory indicators, specific T lymphocyte subpopulations, gene mutations and the response of immuno-targeted combination therapy for HCC was evaluated. RESULTS: The high levels of CD3(+)CD4(+)CD279(+), CD3(+)CD8(+)CD45RO(+)CD62L(+)T lymphocytes and tumor mutational burden (TMB) were associated with good efficacy of the combination therapy (P=0.03, P<0.01 and P=0.03). The high levels of CD3(+)CD4(+)CD28(+) T lymphocytes were associated with poor efficacy of the combination therapy (P=0.02). The high mutation frequency of TP53 and ARID1A appeared in the non-response cohort. In addition, amplification mutation of 11q13-CCND1, FGF3, FGF4, and FGF19 was found in a patient with hyperprogression (HP). CONCLUSIONS: The certain clinical characteristics, laboratory indicators, specific T lymphocyte subpopulations, and gene mutations established in this paper were potential predictive biomarkers for HCC patients treated with combination therapy.