DNA methylation patterns in blood of patients with colorectal cancer and adenomatous colorectal polyps
Elisa Cassinotti
Department of Surgical Sciences, Minimally Invasive Surgery Research Center, University of Insubria, Varese, Italy
Elisa Cassinotti and Joshua Melson contributed equally to this work.
Search for more papers by this authorJoshua Melson
Division of Gastroenterology, Department of Medicine, Rush University Medical Center, Chicago, IL
Elisa Cassinotti and Joshua Melson contributed equally to this work.
Search for more papers by this authorThomas Liggett
Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center, Chicago, IL
Search for more papers by this authorAnatoliy Melnikov
Department of Radiation Oncology, Rush University Medical Center, Chicago, IL
Search for more papers by this authorSohrab Mobarhan
Division of Gastroenterology, Department of Medicine, Rush University Medical Center, Chicago, IL
Search for more papers by this authorLuigi Boni
Department of Surgical Sciences, Minimally Invasive Surgery Research Center, University of Insubria, Varese, Italy
Search for more papers by this authorSergio Segato
Department of Gastroenterology, Azienda Ospedaliero Universitaria, Fondazione Macchi di Varese, Varese, Italy
Search for more papers by this authorCorresponding Author
Victor Levenson
Department of Radiation Oncology, Rush University Medical Center, Chicago, IL
Tel: 312-942-0555
Rush University Medical Center, Department of Radiation Oncology, 1750 W. Harrison Street, Jelke Bldg, 1303, Chicago, IL 60612Search for more papers by this authorElisa Cassinotti
Department of Surgical Sciences, Minimally Invasive Surgery Research Center, University of Insubria, Varese, Italy
Elisa Cassinotti and Joshua Melson contributed equally to this work.
Search for more papers by this authorJoshua Melson
Division of Gastroenterology, Department of Medicine, Rush University Medical Center, Chicago, IL
Elisa Cassinotti and Joshua Melson contributed equally to this work.
Search for more papers by this authorThomas Liggett
Department of Neurological Sciences, Multiple Sclerosis Center, Rush University Medical Center, Chicago, IL
Search for more papers by this authorAnatoliy Melnikov
Department of Radiation Oncology, Rush University Medical Center, Chicago, IL
Search for more papers by this authorSohrab Mobarhan
Division of Gastroenterology, Department of Medicine, Rush University Medical Center, Chicago, IL
Search for more papers by this authorLuigi Boni
Department of Surgical Sciences, Minimally Invasive Surgery Research Center, University of Insubria, Varese, Italy
Search for more papers by this authorSergio Segato
Department of Gastroenterology, Azienda Ospedaliero Universitaria, Fondazione Macchi di Varese, Varese, Italy
Search for more papers by this authorCorresponding Author
Victor Levenson
Department of Radiation Oncology, Rush University Medical Center, Chicago, IL
Tel: 312-942-0555
Rush University Medical Center, Department of Radiation Oncology, 1750 W. Harrison Street, Jelke Bldg, 1303, Chicago, IL 60612Search for more papers by this authorAbstract
Colorectal cancer (CRC) screening rates are currently suboptimal. Blood-based screening could improve rates of earlier detection for CRC and adenomatous colorectal polyps. In this study, we evaluated the feasibility of plasma-based detection of early CRC and adenomatous polyps using array-mediated analysis methylation profiling of 56 genes implicated in carcinogenesis. Methylation of 56 genes in patients with Stages I and II CRC (N = 30) and those with adenomatous polyps (N = 30) were compared with individuals who underwent colonoscopy and were found to have neither adenomatous changes nor CRC. Composite biomarkers were developed for adenomatous polyps and CRC, and their sensitivity and specificity was estimated using five-fold cross validation. Six promoters (CYCD2, HIC1, PAX 5, RASSF1A, RB1 and SRBC) were selected for the biomarker, which differentiated CRC patients and controls with 84% sensitivity and 68% specificity. Three promoters (HIC1, MDG1 and RASSF1A) were selected for the biomarker, which differentiated patients with adenomatous polyps and controls with sensitivity of 55% and specificity of 65%. Methylation profiling of plasma DNA can detect early CRC with significant accuracy and shows promise as a methodology to develop biomarkers for CRC screening.
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