CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients

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™. 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. 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 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. 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. FUND: National Natural Science Foundation of China; Zhejiang Province Science and Technology Program; China Scholarship Council.