Validation of mono-ADP-ribosylated proteins as diagnostic and prognostic tool in oncology
Principal Investigators
Fellow
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.
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Aimi F, Moch H, Schraml P, Hottiger MO. Mod Pathol. 2021 Aug;34(8):1468-1477. doi: 10.1038/s41379-021-00788-9. Epub 2021 Mar 19. PMID: 33742140 Free article.