College of Engineering, Peking University, Beijing 100871, China.
Dept of Hepatopancreatobiliary Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Institute for Precision Medicine, Tsinghua University, Beijing 102218, China; Dept. of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
EBioMedicine. 2019 Aug;46:133-149. doi: 10.1016/j.ebiom.2019.07.044. Epub 2019 Jul 30.
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.
Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs 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.
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 16.5 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.
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. FUND: National Natural Science Foundation of China; Zhejiang Province Science and Technology Program; China Scholarship Council.
对胰腺导管腺癌 (PDAC) 患者进行手术可切除性评估不仅基于影像学，而且具有高度主观性。迫切需要一种客观的方法。我们报告了一种基于表型循环肿瘤细胞 (CTC) 的血液检测在 PDAC 患者术前肿瘤转移和总生存 (OS) 预后评估中的临床价值。
前瞻性地采集 46 例经病理证实的 PDAC 患者手术前的静脉血样本，并使用专门设计的 TU-chip™进行免疫分析。捕获的 CTC 被分为上皮 (E)、间充质和混合 (H) 表型。另外 45 名非肿瘤健康供体提供血液用于细胞系验证研究和 CTC 假阳性定量。
一个由离散组合的 CTC 表型组成的验证多变量模型：“H-CTC≥15.0 CTCs/2ml 或 E-CTC≥11.0 CTCs/2ml”，对转移具有最佳预测性，敏感性为 1.000（95%CI 0.889-1.000），特异性为 0.886（95%CI 0.765-0.972）。使用 Cox 比例风险模型构建的调整后的 Kaplan-Meier 中位 OS，按 E-CTC <11.0 CTCs/2 ml 分层，为 16.5 个月，E-CTC≥11.0 CTCs/2 ml 为 5.5 个月（HR=0.050，95%CI 0.004-0.578，P=0.016）。这些 OS 结果与转移分析的结果一致。
我们的工作表明，H-CTC 是转移的更好预测因子，E-CTC 是 OS 的显著独立预测因子。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。
国家自然科学基金；浙江省科技计划；中国国家留学基金委。
