There remains no reliable biomarker of therapeutic efficacy in hepatocellular carcinoma (HCC) for the PD-L1 inhibitor atezolizumab and bevacizumab (Atezo/Bev). Circulating tumor cells (CTCs) enable the serial collection of living tumor cells. Pre-treatment and serial CTC gene expression changes and tumor histology were evaluated to identify predictors of response to Atezo/Bev. Peripheral blood from 22 patients with HCC treated with Atezo/Bev and 24 patients treated with lenvatinib was serially collected. The RNA expression in CTCs was analyzed using qRT-PCR. Higher PD-L1 expression in pre-treatment CTCs was associated with response and improved prognosis with Atezo/Bev treatment, but not with lenvatinib. There was no correlation between PD-L1 expression in CTCs and that in liver tumor biopsy specimens scored using imaging software. Furthermore, PD-L1 RNA expression in CTCs was dynamically altered by Atezo/Bev, decreasing during effective response and increasing upon progression. CTC-derived RNA collected during Atezo/Bev indicates that patients with higher PD-L1 expression in CTCs at baseline were 3.9 times more responsive to treatment. Therefore, PD-L1 RNA levels in CTCs are an accurate response predictor and may be a monitorable biomarker that changes dynamically to reflect the response during Atezo/Bev treatment.
目前尚缺乏可靠的生物标志物来预测肝细胞癌（HCC）患者对PD-L1抑制剂阿特珠单抗联合贝伐珠单抗（Atezo/Bev）的疗效反应。循环肿瘤细胞（CTCs）能够实现活体肿瘤细胞的连续采集。本研究通过评估治疗前及连续采集的CTCs基因表达变化与肿瘤组织学特征，以识别Atezo/Bev治疗反应的预测因子。研究连续采集了22例接受Atezo/Bev治疗的HCC患者和24例接受仑伐替尼治疗患者的外周血样本，采用qRT-PCR技术分析CTCs中的RNA表达。结果显示，治疗前CTCs中较高的PD-L1表达与Atezo/Bev治疗的反应性及预后改善相关，但与仑伐替尼治疗无关。CTCs中的PD-L1表达与通过影像软件评估的肝肿瘤活检标本中的PD-L1表达无相关性。此外，CTCs中的PD-L1 RNA表达在Atezo/Bev治疗期间呈现动态变化：治疗有效时表达下降，疾病进展时表达升高。基于Atezo/Bev治疗期间采集的CTC来源RNA分析表明，基线时CTCs中PD-L1表达较高的患者对治疗的反应性提高3.9倍。因此，CTCs中的PD-L1 RNA水平可作为精准疗效预测指标，并可能成为可动态监测的生物标志物，实时反映Atezo/Bev治疗过程中的疗效变化。
肿瘤(癌症)患者之家