title: Tumour-associated circulating microparticles: A novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia.
abstract: Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the so-called liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagnosing minimal-invasively the presence and follow up treatment in non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreas carcinoma (PaCa). Tumour-associated MPs (taMPs) were quantified after isolation by centrifugation followed by flow cytometry analysis from the serum of cancer patients with CRC (n = 52), NSCLC (n = 40) and PaCa (n = 11). Healthy subjects (n = 55) or patients with struma nodosa (thyroid nodules) (n = 43) served as negative controls. In all three types of tumour entities, the presence of tumour was associated with an increase of circulating EpCAM+ and EpCAM+CD147+ taMPs. The presence of CD147+EpCAM+ taMPs were specific to tumour-bearing patients thus allowing the specific distinction of malignancies from patients with thyroid nodules. Increased level of EpCAM single positive MPs were, in turn, also detected in patients with thyroid nodules. Importantly, EpCAM+CD147+ taMPs correlated with the measured tumour-volume in CRC patients. EpCAM+ taMPs decreased at 7 days after curative R0 tumour resection suggesting a close dependence with tumour presence. AUROC values (up to 0.85 and 0.90), sensitivity/specificity scores, and positive/negative predictive values indicated a high diagnostic accuracy of EpCAM+CD147+ taMPs. Taken together, EpCAM+CD147+ double positive taMPs could potentially serve as novel promising clinical parameter for cancer screening, diagnosis, surveillance and therapy monitoring.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Willms
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Clara
authors.initials: C
authors.lastname: Müller
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Julich
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Klein
authors.affiliation: Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Schwab
authors.affiliation: Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Güsgen
authors.affiliation: Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Richardsen
authors.affiliation: Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schaaf
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany.|Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Krawczyk
authors.affiliation: Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Krawczyk
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.affiliation: Institute of Translational Immunology and Research Center for Immune Therapy, Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.affiliation: Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Lukacs-Kornek
authors.affiliation: Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany.|Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Kornek
mesh_terms: D000368:Aged; D051926:Basigin / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D055252:Cell-Derived Microparticles / Q000473:pathology*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D055088:Early Detection of Cancer / Q000191:economics / Q000379:methods*; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000073890:Liquid Biopsy / Q000191:economics; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: C497886:BSG protein, human; D014408:Biomarkers, Tumor; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D051926:Basigin
keywords: CD147; CD326; CRC; biomarker; diagnosis