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

Natalia Malara, Maria Laura Coluccio, Tania Limongi, Monica Asande, Valentina Trunzo, Gheorghe Cojoc, Cinzia Raso, Patrizio Candeloro, Gerardo Perozziello, Raffaella Raimondo, Stefania De Vitis, Laura Roveda, Maria Renne, Ubaldo Prati, Vincenzo Mollace, Enzo Di Fabrizio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4324-4331
Number of pages8
JournalSmall
Volume10
Issue number21
DOIs
Publication statusPublished - Nov 12 2014

Keywords

  • folic acid
  • folic acid receptors
  • functionalized surfaces
  • hyper-methylated circulating tumor cells

ASJC Scopus subject areas

  • Biomaterials
  • Engineering (miscellaneous)
  • Biotechnology
  • Medicine(all)

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  • Cite this

    Malara, N., Coluccio, M. L., Limongi, T., Asande, M., Trunzo, V., Cojoc, G., Raso, C., Candeloro, P., Perozziello, G., Raimondo, R., De Vitis, S., Roveda, L., Renne, M., Prati, U., Mollace, V., & Di Fabrizio, E. (2014). Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells. Small, 10(21), 4324-4331. https://doi.org/10.1002/smll.201400498