| International Session（Symposium）1(JSGE・JGES・JSH・JSGS・JSGCS) |
| Thu. October 31st 9:00 - 11:30 Room 11: Portopia Hotel South Wing Topaz |
| Circulating Tumor Cells as Prognostic Biomarker in Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab | |||
| Yosuke Murata1, Takuto Nosaka1, Yasunari Nakamoto1 | |||
| 1Second Department of Internal Medicine, University of Fukui | |||
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| [Background]Circulating tumor cells (CTCs) derived from peripheral blood have attracted attention as a biomarker in monitoring therapeutic efficacy. Combination immunotherapy has promising outcomes in hepatocellular carcinoma (HCC) patients. However, there is no reliable biomarker predicting disease progression. In this study, CTCs were serially collected from HCC patients undergoing combination immunotherapy, Atezolizumab plus Bevacizumab (Atezo+Bev) or Tremelimumab plus Durvalumab (STRIDE). Changes in molecular profiles of CTCs were analyzed to identify effective biomarkers. [Methods]Peripheral bloods were collected from 26 HCC patients treated with Atezo+Bev(n=22) or STRIDE(n=4). CTCs were enriched using RosetteSep and CTC (CD45(-)PanCK(+) cells) numbers were counted using flow cytometry. CTC-derived RNA underwent targeted RNA sequencing of 373 genes with next-generation sequencing (NGS) and qRT-PCR. [Results]CTC numbers of PR/SD group decreased at response evaluation, compared with baseline (212±25 vs.103±23, p<0.01) and increased at PD responses. In NGS analysis of Atezo+Bev group, unsupervised hierarchical clustering classified into two clusters: Patients with elevated TGF-β signaling molecules had poorer responses, whereas those with elevated apoptosis signaling molecules had favorable responses(p<0.05). Furthermore, TGF-β signaling molecules, CDKN2B, GRB2 and PIK3R1 changed earlier, 3weeks after starting Atezo+Bev, significantly correlating with therapeutic response, although this was not significant in STRIDE. [Conclusions]NGS analysis of CTCs showed that changes in TGF-β signaling molecules correlated to therapeutic response. Molecular profiling in CTCs may serve as prognostic biomarkers in HCC patients undergoing Atezo+Bev. |
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Index Term 1: CTC Index Term 2: biomarker |
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