Circulating Tumor Cells with Stem-Like Phenotypes for Diagnosis, Prognosis, and Therapeutic Response Evaluation in Hepatocellular Carcinoma
Circulating Tumor Cells with Stem-Like Phenotypes for Diagnosis, Prognosis, and Therapeutic Response Evaluation in Hepatocellular Carcinoma
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具有干细胞样表型的循环肿瘤细胞用于肝细胞癌的诊断、预后和治疗反应评估
DOI：
10.1158/1078-0432.ccr-17-1753
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发表时间：
2018-05-01
影响因子：
11.5
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Guo, Wei;Sun, Yun-Fan;Fan, Jia
背景：在本研究中，我们评估了具有干细胞表型的循环肿瘤细胞(CTC)在诊断、预后和监测方面的临床价值。方法：研究不同亚型的CTC，并在一项独立验证的多中心患者研究中构建多标记诊断CTC小组(总计1,006例)，包括健康人和慢性乙型肝炎(CHB)、肝硬变(LC)、良性肝病变(BHL)和与乙肝相关的肝细胞癌(HCC)患者，受试者工作特性曲线下面积(AUC-ROC)反映诊断的准确性。结果：CTC仪表组的AUC在训练组为0.88[敏感度=72.5%，特异度=95.0%，阳性预测值(PPV)=92.4，阴性预测值(NPV)=77.8]，验证组为0.93(敏感度=82.1%，特异度=94.2%，PPV=89.9，NPV=89.3)。该专家小组在检测早期和甲胎蛋白阴性的肝细胞癌，以及区分肝细胞癌与慢性乙型肝炎、LC和BHL方面表现同样出色。肿瘤切除后CTC负荷显著降低，持续高CTC负荷的患者术后肿瘤复发倾向明显。预测肿瘤复发的预测意义进一步得到证实[训练：HR=2.692；95%可信区间(CI)，1.617~4.483；P<；0.001；验证：HR=3.127；95%CI，1.360~7.190；P=0.007]。结论：我们的CTC小组在肝癌诊断中具有很高的敏感性和特异性，可作为风险预测和治疗监测的实时参数，使早期决策能够量身定制有效的抗肿瘤策略。(C)2018年AACR。
Background: In the present study, we assessed the clinical value of circulating tumor cells (CTC) with stem-like phenotypes for diagnosis, prognosis, and surveillance in hepatitis B virus (HBV)related hepatocellular carcinoma (HCC) by an optimized qPCR-based detection platform.Methods: Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter patient study with independent validation (total n = 1,006), including healthy individuals and patients with chronic hepatitis B infection (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL), and HBV-related HCC, with area under the receiver operating characteristic curve (AUC-ROC) reflecting diagnostic accuracy. The role of the CTC panel in treatment response surveillance and its prognostic significance were further investigated.Results: The AUC of the CTC panel was 0.88 in the training set [sensitivity = 72.5%, specificity = 95.0%, positive predictive value (PPV) = 92.4, negative predictive value (NPV) = 77.8] and 0.93 in the validation set (sensitivity = 82.1%, specificity = 94.2%, PPV = 89.9, NPV = 89.3). This panel performed equally well in detecting early-stage and a-fetoprotein-negative HCC, as well as differentiating HCC from CHB, LC, and BHL. The CTC load was decreased significantly after tumor resection, and patients with persistently high CTC load showed a propensity of tumor recurrence after surgery. The prognostic significance of the CTC panel in predicting tumor recurrence was further confirmed [training: HR = 2.692; 95% confidence interval (CI), 1.617-4.483; P < 0.001; and validation: HR = 3.127; 95% CI, 1.360-7.190; P = 0.007].Conclusions: Our CTC panel showed high sensitivity and specificity in HCC diagnosis and could be a real-time parameter for risk prediction and treatment monitoring, enabling early decision-making to tailor effective antitumor strategies. (C) 2018 AACR.