Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells
Coluccio, Maria Laura
De Vitis, Stefania
Di Fabrizio, Enzo M.
KAUST DepartmentPhysical Sciences and Engineering (PSE) Division
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AbstractAlthough the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor's stadiation, therapy, and early relapsing lesions. Within surface's bio-functionalization and cell's isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient's blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy.© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
SponsorsThis work was partially supported by the Grants from the PON "Nuove strategie nanotecnologiche per la messa a punto di farmaci e presidi diagnostici diretti verso cellule cancerose circolanti" project (code: PON01_02782), the Interregional Research Centre for Food Safety & Health (IRC_FSC) project (cod. PON a3-00359) granted to the Department of Health Science of the University Magna Graecia of Catanzaro, the FIRB "Rete Nazionale di Ricerca sulle Nanoscienze ItalNanoNet" project (cod. RBPR05JH2P_010, CUP B41J09000110005) granted to the nanotechnology laboratory of the Department of Experimental Medicine of the University of Magna Graecia of Catanzaro and the "Fondo Sociale Europeo - POR Calabria FSE 2007/2013" Program. The authors thank R. Giammaria for revising the English text.