Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment,tracing a biomarker signature specific for this tumor |
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| Authors: | Ludovic Barault Vera Piera Leoni Pia Sulas Luigi Zorcolo Angelo Restivo Francesco Cabras Federica Fortunato Cesare Zavattari Liliana Varesco Viviana Gismondi Maria Rosaria De Miglio Antonio Mario Scanu Federica Colombi Pasquale Lombardi Ivana Sarotto Eleonora Loi Francesco Leone Silvia Giordano Federica Di Nicolantonio Amedeo Columbano Patrizia Zavattari |
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| Institution: | 1. Department of Oncology, University of Torino, Turin, Italy;2. Candiolo Cancer Institute‐FPO, IRCCS, Candiolo, Italy;3. Unit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy;4. Department of Surgery, Colorectal Surgery Center, University of Cagliari, Cagliari, Italy;5. Independent Researcher, Machine Learning, Lucca, Italy;6. Unit of Hereditary Cancer, IRCCS AOU San Martino‐IST, Genoa, Italy;7. Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy;8. Unit of Biology and Genetics, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy |
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| Abstract: | Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment. The panel discriminates CRCs and adenomas from peritumoral and normal mucosa with very high specificity (100%) and sensitivity (99.9%). Interestingly, over 70% of the hypermethylated islands resulted in downregulation of gene expression. To establish the possible usefulness of these non‐invasive markers for detection of colon cancer, we selected three biomarkers and identified the presence of altered methylation in stool DNA and plasma cell‐free circulating DNA from CRC patients. |
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