Diagnostic and prognostic role of cell‐free DNA testing for colorectal cancer patients

• Published in: International journal of cancer 2017-04, Vol.140 (8), p.1888-1898
• Main Authors: Bedin, Chiara, Enzo, Maria Vittoria, Del Bianco, Paola, Pucciarelli, Salvatore, Nitti, Donato, Agostini, Marco
• Format: Article
• Language: English
• Subjects: Adenoma; Aged; Alu Elements - genetics; ALU‐based; Biomarkers, Tumor - blood; Biopsy; Cancer; cell‐free DNA; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - blood; Colorectal Neoplasms - pathology; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; DNA, Neoplasm - blood; DNA, Neoplasm - genetics; Epigenesis, Genetic; Female; Frizzled-related protein 1; Humans; liquid biopsy; Male; Medical prognosis; Medical research; Medical screening; methylation; Middle Aged; Prognosis; Promoter Regions, Genetic; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.30565

Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU‐based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n = 114) in comparison to healthy subjects (n = 56) and patients with adenomatous lesions (n = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type‐specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease. What's new? Liquid biopsy of circulating cell‐free DNA (cfDNA) is an emerging approach in cancer screening that can potentially facilitate the early detection of tumor‐derived molecular alterations. In our study, designed to explore the utility of liquid biopsy in colorectal cancer (CRC) detection, cfDNA quantification was found to be sufficiently capable of differentiating CRC patients from healthy controls and from patients with adenomatous polyps. Moreover, among CRC patients, those with higher cfDNA levels experienced worse prognosis, suggesting that cfDNA dosage predicts survival. CRC detection through cfDNA quantification may be improved through the addition of methylation biomarkers.