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Validation of mono-­ADP-­ribosylated proteins as diagnostic and prognostic tool in oncology

Principal Investigators

Micheal Hottiger, Department of Molecular Mechanisms of Disease, University of Zurich
Peter Schraml, Department of Pathology and Molecular Pathology, University Hospital Zurich

Fellow

Fabio Aimi, PhD

Keywords

KIDNEY CANCER, ADP-RIBOSYLATION, BIOMARKERS

Summary

Tumor stage-specific and prognostic biomarkers are important tools to better characterize and understand the behavior of cancer and are an integral part of the decision-making process along the course of the disease. ADP-ribosylation is a phylogenetically ancient, reversible posttranslational modification that involves the covalent transfer of one (i.e. MARylation), or several, ADP-ribose (ADPr) moieties (i.e. PARylation) from NAD+, which links this modification to the cell’s metabolic and redox state. Using different chemical approaches, we recently could generate ADP-ribosylated peptides allowing the generation of a first polyclonal antibody against MARylation. Immunostainings of clear cell Renal Cell Carcinoma (ccRCC) tissue microarrays identified two different anti-MAR staining patterns, of which one correlated with better overall survival. Based on the current knowledge on stress and cell death-induced ADP-ribosylation as well as on our preliminary data, we hypothesize that protein MARylation is a potential diagnostic and prognostic biomarker for the analysis of human cancers. Identifying and knowing the “ADP-ribosylation status” might thus be an integral part of tumor staging and patient stratification to optimize personalized cancer treatments in the future.