Patient-matched analysis identifies deregulated networks in prostate cancer to guide personalized therapeutic intervention.
Fiche publication
Date publication
janvier 2021
Journal
American journal of cancer research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich, Dr MENDOZA Manuel
Tous les auteurs :
Kumar A, Kasikci Y, Badredine A, Azzag K, Quintyn Ranty ML, Zaidi F, Aragou N, Mazerolles C, Malavaud B, Mendoza-Parra MA, Vandel L, Gronemeyer H
Lien Pubmed
Résumé
Prostate cancer (PrCa) is the second most common malignancy in men. More than 50% of advanced prostate cancers display the TMPRSS2-ERG fusion. Despite extensive cancer genome/transcriptome data, little is known about the impact of mutations and altered transcription on regulatory networks in the PrCa of individual patients. Using patient-matched normal and tumor samples, we established somatic variations and differential transcriptome profiles of primary ERG-positive prostate cancers. Integration of protein-protein interaction and gene-regulatory network databases defined highly diverse patient-specific network alterations. Different components of a given regulatory pathway were altered by novel and known mutations and/or aberrant gene expression, including deregulated ERG targets, and were validated by using a novel methodology. Consequently, different sets of pathways were altered in each individual PrCa. In a given PrCa, several deregulated pathways share common factors, predicting synergistic effects on cancer progression. Our integrated analysis provides a paradigm to identify druggable key deregulated factors within regulatory networks to guide personalized therapies.
Mots clés
Cancer systems biology, patient-matched deregulated networks, personalized therapy, prostate cancer
Référence
Am J Cancer Res. 2021 ;11(11):5299-5318