Tumour-associated circulating microparticles: A novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia
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Arnulf Willms1, Clara Müller2, Henrike Julich2, Niklas Klein2, Robert Schwab1, Christoph Güsgen1, Ines Richardsen1, Sebastian Schaaf1, Marcin Krawczyk2,3, Marek Krawczyk4, Frank Lammert2, Detlef Schuppan5, Veronika Lukacs-Kornek2, Miroslaw Kornek1,2
1Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany
2Department of Medicine II, Saarland University Medical Center, Homburg/Saar, Germany
3Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
4Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
5Institute of Translational Immunology and Research Center for Immune Therapy, Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
Miroslaw Kornek, e-mail: [email protected]
Keywords: biomarker, CD147, CD326, CRC, diagnosis
Received: March 07, 2016 Accepted: April 02, 2016 Published: April 26, 2016
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.
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