CTC Phenotyping for a Preoperative Assessment of Tumor Metastasis and Overall Survival of Pancreatic Cancer Patients

Abstract

Purpose: Our work investigated the clinical value of a phenotypic circulating tumor cell (CTC)-based blood test by suggesting its use for a preoperative prognostic assessment of tumor metastasis and overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC) patients. Experimental Design: Venous blood samples from 46 pathologically confirmed PDAC patients comprising 35 local (stage I-III) subjects as the control cohort and 11 metastatic (stage IV) subjects as the case cohort were collected prospectively before surgery and immunoassayed using a specially designed TU-chipTM. Captured CTCs were differentiated into epithelial (E), mesenchymal (M) and hybrid (H) phenotypes. Results: A validated multivariable model consisting of disjunctively combined CTC phenotypes: ≥ 15.0 CTCs/2 OR E-CTC ≥ 11.0 CTCs/2 ml produced 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 constructed using Cox proportional-hazard models and stratified for E-CTC < 11 CTCs/2ml was 16.5 months and for E-CTC ≥ 11.0 CTCs/2ml was 5.5 months (HR=0.050, 95% CI 0.004-0.578, P=0.016). These OS results were consistent with the outcome of the metastatic analysis; the median survival of metastatic patients was less than 6 months but for surgically resected local patients, it was almost 1.5 years. Conclusions: 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 de-veloped into a reliable and accurate blood test for metastatic and OS assessments of PDAC patients. Funding: Key Project of the Science and Technology Program of Zhejiang, Grant No: 2014C03028 and China Scholarship Council (via a scholarship to K.S.C.). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: This work was performed in accordance to the Declaration of Helsinki with the research protocol approved by the hospital institutional review board of the Chinese Academy of Medical Sciences & Peking Union Medical College Hospital.