Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer.
Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation.



Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC.



We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ⩾3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001).



CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|Veteran's Health Administration, Greater Los Angeles, Department of Surgery, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
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Ankeny
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|Veteran's Health Administration, Greater Los Angeles, Department of Surgery, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
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Court
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Hou
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Li
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Song
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Wu
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Chen
California NanoSystems Institute, University of California, 570 Westwood Plaza, Los Angeles, CA 90095, USA.
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Lee
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Lin
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|Veteran's Health Administration, Greater Los Angeles, Department of Surgery, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
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Sho
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Rochefort
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Girgis
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Yao
UCLA Center for Pancreatic Diseases, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|Department of Hematology/Oncology, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Wainberg
UCLA Center for Pancreatic Diseases, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|Department of Gastroenterology, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Muthusamy
UCLA Center for Pancreatic Diseases, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|Department of Gastroenterology, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Watson
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|UCLA Center for Pancreatic Diseases, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Donahue
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|UCLA Center for Pancreatic Diseases, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Hines
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|UCLA Center for Pancreatic Diseases, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Reber
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Graeber
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California, Los Angeles, 570 Westwood Plaza, Los Angeles, CA 90095-1770, USA.
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Tseng
Department of Surgery, University of California Los Angeles, 575 Westwood Plaza, Los Angeles, CA 90095, USA.|Veteran's Health Administration, Greater Los Angeles, Department of Surgery, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.|UCLA Center for Pancreatic Diseases, 575 Westwood Plaza, Los Angeles, CA 90095, USA.
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Tomlinson
D014408:Biomarkers, Tumor / Q000097:blood; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000473:pathology*; D015331:Cohort Studies; D006801:Humans; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000473:pathology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)