title: Immunomediated Pan-cancer Regulation Networks are Dominant Fingerprints After Treatment of Cell Lines with Demethylation.
abstract: Pan-cancer studies are particularly relevant not only for addressing the complexity of the inherently observed heterogeneity but also for identifying clinically relevant features that may be common to the cancer types. Immune system regulations usually reveal synergistic modulation with other cancer mechanisms and in combination provide insights on possible advances in cancer immunotherapies. Network inference is a powerful approach to decipher pan-cancer systems dynamics. The methodology proposed in this study elucidates the impacts of epigenetic treatment on the drivers of complex pan-cancer regulation circuits involving cell lines of five cancer types. These patterns were observed from differential gene expression measurements following demethylation with 5-azacytidine. Networks were built to establish associations of phenotypes at molecular level with cancer hallmarks through both transcriptional and post-transcriptional regulation mechanisms. The most prominent feature that emerges from our integrative network maps, linking pathway landscapes to disease and drug-target associations, refers primarily to a mosaic of immune-system crosslinked influences. Therefore, characteristics initially evidenced in single cancer maps become motifs well summarized by network cores and fingerprints.
authors.affiliation: Laboratory of Integrative Systems Medicine (LISM), Institute of Clinical Physiology, National Research Council of Italy (CNR), Pisa, Italy.; Medical Oncology Department, MIRO, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Mariama
authors.initials: M
authors.lastname: El Baroudi
authors.affiliation: Cancer Therapy UOS, Institute of Clinical Phsyiology, National Research Council of Italy (CNR), Siena, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cinti
authors.affiliation: Laboratory of Integrative Systems Medicine (LISM), Institute of Clinical Physiology, National Research Council of Italy (CNR), Pisa, Italy.; Center for Computational Science, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Enrico
authors.initials: E
authors.lastname: Capobianco
keywords: demethylation; drug-target maps; gene networks; immunomediated regulation; pan-cancer