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.
免疫检查点抑制剂在肝细胞癌（HCC）患者中展现出良好的疗效，但目前尚缺乏可靠的生物标志物来预测疾病进展。来源于外周血的循环肿瘤细胞（CTCs）在监测治疗效果方面受到关注。本研究连续收集接受阿特珠单抗联合贝伐珠单抗（Atezo+Bev）治疗的HCC患者的CTCs，通过分析分子表达及CTC数量的变化以寻找有效的生物标志物。结果显示，Atezo+Bev治疗期间CTC数量的变化可反映肿瘤体积。基于新一代测序（NGS）的靶向RNA测序分析发现，转化生长因子（TGF）-β信号通路分子表达升高的患者治疗反应较差，而凋亡信号通路分子表达升高的患者则呈现良好反应。此外，与CTC数量变化相比，CTC中TGF-β信号通路分子表达的变化能更准确、更及时地预测治疗反应。总体而言，对CTC来源RNA的NGS分析表明，TGF-β信号通路分子的变化较CTC数量变化能更早预测治疗反应。这些发现提示，CTC中TGF-β分子表达的变化可能作为新型生物标志物，用于早期预测接受Atezo+Bev治疗的不可切除HCC患者的治疗反应。
肿瘤(癌症)患者之家