Murata Yosuke, Nosaka Takuto, Akazawa Yu, Tanaka Tomoko, Takahashi Kazuto, Naito Tatsushi, Matsuda Hidetaka, Ohtani Masahiro, Nakamoto Yasunari
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Cancers (Basel). 2024 Jun 29;16(13):2410. doi: 10.3390/cancers16132410.
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）患者中取得了令人鼓舞的疗效；然而，目前尚无可靠的生物标志物来预测疾病进展。源自外周血的循环肿瘤细胞（CTC）在监测治疗效果方面受到了关注。在本研究中，对接受阿替利珠单抗联合贝伐单抗（阿替利珠单抗+贝伐单抗）治疗的HCC患者连续采集CTC，并分析分子表达和CTC数量的变化，以确定有效的生物标志物。阿替利珠单抗+贝伐单抗治疗期间CTC数量的变化反映了肿瘤体积。采用下一代测序（NGS）进行靶向RNA测序显示，转化生长因子（TGF）-β信号分子升高的患者反应较差，而凋亡信号分子升高的患者反应良好。此外，与CTC计数的变化相比，CTCs中TGF-β信号分子表达的变化能准确、迅速地预测治疗反应。总体而言，对CTC衍生RNA的NGS分析表明，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，CTCs中TGF-β分子表达的变化可作为接受阿替利珠单抗+贝伐单抗治疗的不可切除HCC患者早期预测治疗反应的新型生物标志物。
