Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells

Abstract
Although 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.

Citation
Malara, N., Coluccio, M. L., Limongi, T., Asande, M., Trunzo, V., Cojoc, G., … Di Fabrizio, E. (2014). Folic Acid Functionalized Surface Highlights 5-Methylcytosine-Genomic Content within Circulating Tumor Cells. Small, n/a–n/a. doi:10.1002/smll.201400498

Acknowledgements
This 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.

Publisher
Wiley

Journal
Small

DOI
10.1002/smll.20140049810.1002/smll.201470135

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