Alu cell-free DNA concentration,Alu index,and LINE-1 hypomethylation as a cancer predictor |
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| Affiliation: | 1. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil;2. Laboratório de Marcadores Circulantes, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil;3. Instituto Nacional de Câncer (INCA-HCIII), Rio de Janeiro, Brazil;1. Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 26 Plocka St., Warsaw 01-138, Poland;2. Department of Thoracic Surgery, National Institute of Tuberculosis and Lung Diseases, 26 Plocka St., Warsaw 01-138, Poland;3. Department of Pathomorphology, National Institute of Tuberculosis and Lung Diseases, 26 Plocka St., Warsaw 01-138, Poland;1. Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, No.42, Baiziting, Nanjing City 210009, Jiangsu Province, China;2. Department of Hematology, The First Affiliated Hospital of Wannan Medical College, No.2, Zheshan West Road, Wuhu City 241001, Anhui Province, China;3. Department of Pathology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, No.42, Baiziting, Nanjing City 210009, Jiangsu Province, China;4. Soochow University, No.1, Shizi Street, Suzhou city 215006, Jiangsu Province, China;5. Clinic laboratory of Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences, No.12, Jiangwangmiao Street, Xuanwu District, Nanjing City 210042, Jiangsu Province, China;6. Department of Radiotherapy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, No.42, Baiziting, Nanjing City 210009, Jiangsu Province, China;7. Department of Medical Oncology, Nantong Tumor Hospital, No.48, Qingnian West Road, Nantong city 226000, Jiangsu Province, China;8. Department of Medical Oncology, Lanxi County People''s Hospital. No.65, North Street of Langxi County, 242100, Anhui Province, China |
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| Abstract: | IntroductionThe liquid biopsy approach, a less-invasive diagnostic tool, enables the detection of disease-specific genetic and epigenetic aberrations. Approximately 66–69% of the human genome may be composed of transposable repetitive elements, including Alu and LINE-1. This study aimed to investigate whether Alu-derived cell-free DNA (cfDNA) concentrations, Alu index, and LINE-1 methylation could be used to distinguish patients with cancers from healthy individuals.MethodsTwo sets of primers, shorter and longer Alu fragments, were used to amplify Alu elements, followed by the quantitation of Alu DNA concentration and its integrity index. LINE-1 methylation status was then analyzed with quantitative PCR using methylation- and unmethylation-specific TaqMan probes.ResultsBoth Alu index and LINE-1 methylation level were significantly different in comparison between patients with lung or breast cancer and the healthy controls. The area under the ROC curve of the Alu index and LINE-1 hypomethylation was 0.742 and 0.848 for lung cancer, respectively, and 0.724 and 0.890 for breast cancer, respectively. However, Alu longer fragment DNA concentration was significantly correlated with Alu index in comparison to LINE-1 hypomethylation. Regression analysis suggested that the LINE-1 methylation level, rather than the Alu index, was a good discriminator for lung and breast cancers.ConclusionsThis study investigated the genome-wide Alu index and LINE-1 methylation status; their associations with cancers suggested that these combinatory panels could be implemented as a triage test to discriminate cancer patients from healthy individuals. |
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| Keywords: | Cell-free DNA Biomarker DNA methylation |
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