Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment, tracing a biomarker signature specific for this tumor

Antonio Fadda, Davide Gentilini, Loredana Moi, 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 LeoneSilvia Giordano, Federica Di Nicolantonio, Amedeo Columbano, Patrizia Zavattari

Research output: Contribution to journalArticle

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.
Original languageItalian
Pages (from-to)907-920
Number of pages14
JournalInternational Journal of Cancer
Volume143
Issue number4
DOIs
Publication statusPublished - Aug 15 2018

Cite this

Fadda, A., Gentilini, D., Moi, L., Barault, L., Leoni, V. P., Sulas, P., Zorcolo, L., Restivo, A., Cabras, F., Fortunato, F., Zavattari, C., Varesco, L., Gismondi, V., De Miglio, M. R., Scanu, A. M., Colombi, F., Lombardi, P., Sarotto, I., Loi, E., ... Zavattari, P. (2018). Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment, tracing a biomarker signature specific for this tumor. International Journal of Cancer, 143(4), 907-920. https://doi.org/10.1002/ijc.31380