CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients
CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients
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CTC 表型分析用于术前评估胰腺导管腺癌的肿瘤转移和总体生存率。
DOI：
10.1016/j.ebiom.2019.07.044
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发表时间：
2019-08-01
期刊：
影响因子：
11.1
通讯作者：
Han, Ray P. S.
中科院分区：
文献类型：
--
作者：
Sun, Yukun;Wu, Guangdong;Han, Ray P. S.
背景：对胰腺导管腺癌(PDAC)患者的手术可切除性的评估不仅基于影像，而且具有高度的主观性。迫切需要一种客观的方法。我们报告了基于表型循环肿瘤细胞(CTC)的血液检测在评估PDAC患者术前肿瘤转移和总生存期(OS)方面的临床价值。方法：前瞻性采集46例经病理证实的PDAC患者的手术前静脉血样本，并使用专门设计的TU芯片(TM)进行免疫检测。将捕获的CFCs分化为上皮型(E)、间叶型(MSC)和混合型(H)。另有45名非肿瘤性健康献血者提供了血液换细胞系验证研究和CTC假阳性定量。结果：由分离组合的CTC表型组成的经验证的多变量模型：“H-CTC>；=15.0CTCs/2ml或E-CTC>；=11.0CTCs/2ml”产生了最优的转移预测模型，其敏感度为1.000(95%CI 0.889-1.000)，特异度为0.886(95%CI 0.765-0.972)。用COX比例风险模型建立的调整后的Kaplan-Meier中位OS，分层为E-CTC和11.0CTCS/2ml分别为165月和5.5月(HR=0.050，95%CI为0.004~0.578，P=0.016)。这些OS的结果与转移分析的结果一致。解释：我们的工作表明H-CTC是更好的转移预测因子，而E-CTC是OS显著的独立预测因子。CTC表型模型有可能发展成为一种可靠和准确的血液检测方法，用于PDAC患者的转移和OS评估。(C)2019年提交人。爱思唯尔出版公司(Elsevier B.V.)
Background: The evaluation for surgical resectability of pancreatic ductal adenocarcinoma (PDAC) patients is not only imaging-based but highly subjective. An objective method is urgently needed. We report on the clinical value of a phenotypic circulating tumor cell (CTC)-based blood test for a preoperative prognostic assessment of tumor metastasis and overall survival (OS) of PDAC patients.Methods: Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip (TM). Captured CFCs were differentiated into epithelial (E), mesenchymal and hybrid (H) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification.Findings: A validated multivariable model consisting of disjunctively combined CTC phenotypes: "H-CTC >= 15.0 CTCs/2ml OR E-CTC >= 11.0 CTCs/2ml" generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889-1.000) and specificity of 0.886 (95% CI 0.765-0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E-CTC < 11.0 CTCs/2 ml was 165 months and for E-CTC >= 11.0 CTCs/2 ml was 5.5 months (HR = 0.050, 95% CI 0.004-0.578, P = .016). These OS results were consistent with the outcome of the metastatic analysis.Interpretation: Our work suggested that H-CTC is a better predictor of metastasis and E-CTC is a significant independent predictor of OS. The CTC phenotyping model has the potential to be developed into a reliable and accurate blood test for metastatic and OS assessments of PDAC patients. (C) 2019 The Authors. Published by Elsevier B.V.