title: 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.
authors.affiliation: Italian Institute of Technology, Arnesano, Lecce, Italy; BIONEM, University of Magna Graecia, Campus S. Venuta, Viale Europa, 88100, Catanzaro, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Malara
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Coluccio
authors.forename: Tania
authors.initials: T
authors.lastname: Limongi
authors.forename: Monica
authors.initials: M
authors.lastname: Asande
authors.forename: Valentina
authors.initials: V
authors.lastname: Trunzo
authors.forename: Gheorghe
authors.initials: G
authors.lastname: Cojoc
authors.forename: Cinzia
authors.initials: C
authors.lastname: Raso
authors.forename: Patrizio
authors.initials: P
authors.lastname: Candeloro
authors.forename: Gerardo
authors.initials: G
authors.lastname: Perozziello
authors.forename: Raffaella
authors.initials: R
authors.lastname: Raimondo
authors.forename: Stefania
authors.initials: S
authors.lastname: De Vitis
authors.forename: Laura
authors.initials: L
authors.lastname: Roveda
authors.forename: Maria
authors.initials: M
authors.lastname: Renne
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Prati
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mollace
authors.forename: Enzo
authors.initials: E
authors.lastname: Di Fabrizio
mesh_terms: D044503:5-Methylcytosine / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000235:genetics; D001774:Blood Chemical Analysis / Q000295:instrumentation* / Q000379:methods; D002478:Cells, Cultured; D019175:DNA Methylation; D004797:Enzyme-Linked Immunosorbent Assay; D005492:Folic Acid / Q000737:chemistry* / Q000494:pharmacology; D052138:Genes, Neoplasm; D006801:Humans; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D013499:Surface Properties; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D044503:5-Methylcytosine; D005492:Folic Acid
keywords: folic acid; folic acid receptors; functionalized surfaces; hyper-methylated circulating tumor cells