Background:Atezolizumab plus bevacizumab and lenvatinib are standard treatments for advanced hepatocellular carcinoma, but conventional tumor markers such as alpha-fetoprotein and des-gamma-carboxy prothrombin have a limited ability to reflect treatment responses. Circulating tumor cells with cancer stem cell characteristics have emerged as promising biomarkers. We examined the dynamics of cancer stem cell-related circulating tumor cell subsets and tumor markers at early and maximal response phases in patients with unresectable hepatocellular carcinoma undergoing systemic therapy.Methods:Sixty-two patients treated with either atezolizumab plus bevacizumab or lenvatinib were retrospectively analyzed. Peripheral blood was collected at baseline, during the early phase (during one to three months), and at maximal response. Circulating tumor cell subsets expressing cancer stem cell markers (CD90, epithelial cell adhesion molecule; CD133, vimentin) were assessed using multiparametric flow cytometry and compared with alpha-fetoprotein and des-gamma-carboxy prothrombin.Results:Early decreases in CD90-positive circulating tumor cells after therapy were associated with tumor shrinkage, longer periods of progression-free survival in both groups, and prolonged overall survival in the atezolizumab plus bevacizumab group. By contrast, early changes in alpha-fetoprotein and des-gamma-carboxy prothrombin were not consistently related to tumor size, progression-free survival, or overall survival. At maximal response, changes in CD90-positive circulating tumor cells reflected tumor burden more accurately than alpha-fetoprotein or des-gamma-carboxy prothrombin.Conclusions:These findings indicate that cancer stem cell-related circulating tumor cell subsets, particularly CD90-positive cells, may serve as valuable biomarkers for monitoring treatment response and predicting prognosis in unresectable hepatocellular carcinoma. CD90-positive circulating tumor cells perform dynamic monitoring superior to conventional markers such as alpha-fetoprotein and des-gamma-carboxy prothrombin.
背景：阿特珠单抗联合贝伐珠单抗以及仑伐替尼是晚期肝细胞癌的标准治疗方案，但传统肿瘤标志物如甲胎蛋白和脱-γ-羧基凝血酶原在反映治疗反应方面能力有限。具有癌症干细胞特征的外周血循环肿瘤细胞已成为有前景的生物标志物。本研究旨在探讨接受系统治疗的不可切除肝细胞癌患者，在早期和最大反应阶段癌症干细胞相关循环肿瘤细胞亚群及肿瘤标志物的动态变化。 方法：回顾性分析62例接受阿特珠单抗联合贝伐珠单抗或仑伐替尼治疗的患者。分别于基线期、早期（治疗后1-3个月内）及最大反应期采集外周血样本。通过多参数流式细胞术检测表达癌症干细胞标志物（CD90、上皮细胞黏附分子；CD133、波形蛋白）的循环肿瘤细胞亚群，并与甲胎蛋白和脱-γ-羧基凝血酶原水平进行比较。 结果：治疗后早期CD90阳性循环肿瘤细胞的减少与肿瘤缩小、两组患者更长的无进展生存期相关，且在阿特珠单抗联合贝伐珠单抗组中与总生存期延长显著相关。相比之下，甲胎蛋白和脱-γ-羧基凝血酶原的早期变化与肿瘤大小、无进展生存期或总生存期无稳定关联。在最大反应期，CD90阳性循环肿瘤细胞的变化比甲胎蛋白或脱-γ-羧基凝血酶原更能准确反映肿瘤负荷。 结论：这些发现表明，癌症干细胞相关循环肿瘤细胞亚群，特别是CD90阳性细胞，可作为监测不可切除肝细胞癌治疗反应和预测预后的重要生物标志物。CD90阳性循环肿瘤细胞在动态监测方面优于甲胎蛋白和脱-γ-羧基凝血酶原等传统标志物。
肿瘤(癌症)患者之家