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Abstract：
Immune checkpoint inhibitors have promising outcomes in patients with hepatocellular carcinoma (HCC); however, there is no reliable biomarker for predicting disease progression. Circulating tumor cells (CTCs) derived from peripheral blood have attracted attention in monitoring therapeutic efficacy. In this study, CTCs were serially collected from HCC patients undergoing atezolizumab plus bevacizumab (Atezo+Bev), and changes in molecular expression and CTC numbers were analyzed to identify effective biomarkers. Changes in CTC numbers during Atezo+Bev reflected the tumor volume. Targeted RNA sequencing with next-generation sequencing (NGS) revealed that patients with elevated transforming growth factor (TGF)-β signaling molecules had a poorer response, whereas those with elevated apoptosis signaling molecules had a favorable response. In addition, compared with changes in CTC counts, changes in TGF-β signaling molecule expression in CTCs accurately and promptly predicted treatment response. Overall, NGS analysis of CTC-derived RNA showed that changes in TGF-β signaling molecules predict treatment response earlier than changes in CTC counts. These findings suggest that changes in the expression of TGF-β molecules in CTCs could serve as novel biomarkers for the early prediction of therapeutic response in patients with unresectable HCC undergoing Atezo+Bev.
摘要：
免疫检查点抑制剂在肝细胞癌（HCC）患者中有希望的结果;然而，没有可靠的生物标志物来预测疾病进展.来自外周血的循环肿瘤细胞（CTC）在监测治疗效果方面引起了关注。在这项研究中,CTC从接受阿特珠单抗加贝伐单抗（Atezo+Bev）的HCC患者中连续收集，并分析分子表达和CTC数量的变化以鉴定有效的生物标志物。Atezo+Bev期间CTC数量的变化反映了肿瘤体积。靶向RNA测序与下一代测序（NGS）显示，转化生长因子（TGF）-β信号分子升高的患者反应较差，而那些细胞凋亡信号分子升高的患者有良好的反应。此外,与CTC计数的变化相比，CTC中TGF-β信号分子表达的变化能准确、及时地预测治疗反应。总的来说,CTC衍生RNA的NGS分析显示TGF-β信号分子的变化比CTC计数的变化更早预测治疗反应。这些发现表明，CTC中TGF-β分子表达的变化可以作为新的生物标志物，用于早期预测接受AtezoBev的不可切除HCC患者的治疗反应。
