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

Sun Y 1 , Wu G 2 , Cheng KS 1 , Chen A 1 , Neoh KH 1 , Chen S 1 Show all authors , Tang Z 1 , Lee PF 3 , Dai M 4 , Han RPS 5

Affiliations 

  • 1 College of Engineering, Peking University, Beijing 100871, China
  • 2 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
  • 3 Dept. of Mechanical & Materials Engineering, University Tunku Abdul Rahman, Bandar Sungai Long, Selangor, Malaysia
  • 4 Dept. of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address: daimh@pumch.cn
  • 5 College of Engineering, Peking University, Beijing 100871, China; Integrated Chinese & Western Medicine Oncology Research Center, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, China.. Electronic address: ray-han@jxutcm.edu.cn
EBioMedicine, 2019 Aug;46:133-149.
PMID: 31375425 DOI: 10.1016/j.ebiom.2019.07.044

Abstract

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 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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