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Genetic markers and phosphoprotein forms of beta-catenin pß-Cat552 and pß-Cat675 are prognostic biomarkers of cervical cancer.
Scholl, Suzy M; Beal, Jonas; de Koning, Leanne; Girard, Elodie; Popovic, Marina; de la Rochefordière, Anne; Lecuru, Fabrice; Fourchotte, Virginie; Ngo, Charlotte; Floquet, Anne; Berns, Els Mjj; Kenter, Gemma; Gestraud, Pierre; von der Leyen, Heiko; Lecerf, Charlotte; Puard, Vincent; Roman, Sergio Roman; Latouche, Aurelien; Kereszt, Attila; Balint, Balazs; Rouzier, Roman; Kamal, Maud.
Afiliação
  • Scholl SM; Department of Drug Development and Innovation, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France. Electronic address: suzy.scholl@gmail.com.
  • Beal J; Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, 75005 Paris, France.
  • de Koning L; Department of Translational Research, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.
  • Girard E; Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, 75005 Paris, France.
  • Popovic M; Oncology Institute of Vojvodina, Put doktora Goldmana, 421204 Sremska Kamenica, Serbia.
  • de la Rochefordière A; Department of Radiotherapy, Institut Curie, PSL Research University, 75005 Paris, France.
  • Lecuru F; Department of Surgery, Institut Curie, PSL Research University, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.
  • Fourchotte V; Department of Surgery, Institut Curie, PSL Research University, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.
  • Ngo C; Service de chirurgie cancérologique gynécologique et du sein, Hôpital Européen Georges Pompidou, APHP et faculté de médecine, Université Paris Descartes, France.
  • Floquet A; Chirurgie onco-gynécologique and Oncology, Institut Bergonié, Centre Régional de Lutte contre le Cancer Bordeaux-Aquitaine, France.
  • Berns EM; Dept Medical Oncology, Erasmus MC, 3000 CA Rotterdam, Netherlands.
  • Kenter G; Department of Drug Development and Innovation, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France; Department of Gynaecologic Oncology Amsterdam, Amsterdam UMC and The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands.
  • Gestraud P; Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, 75005 Paris, France.
  • von der Leyen H; Department of Drug Development and Innovation, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France; Hannover Clinical Trial Center, Hannover Medical School Germany.
  • Lecerf C; Department of Drug Development and Innovation, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.
  • Puard V; Department of Translational Research, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.
  • Roman SR; Department of Translational Research, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.
  • Latouche A; Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, 75005 Paris, France; Conservatoire national des arts et métiers, Paris, France.
  • Kereszt A; Department of Drug Development and Innovation, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France; SeqOmics Biotechnology Ltd, Vallalkozok utja 7, Morahalom, Hungary.
  • Balint B; Department of Drug Development and Innovation, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France; Department of Translational Research, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.
  • Rouzier R; Department of Surgery, Institut Curie, PSL Research University, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France; Bioinformatics and Computational Systems Biology of Cancer, PSL Research University, Mines Paris Tech, INSERM U900, 75005 Paris, France.
  • Kamal M; Department of Drug Development and Innovation, Institut Curie, PSL Research University, 75005 Paris & 92210 Saint-Cloud, France.
EBioMedicine ; 61: 103049, 2020 Nov.
Article em En | MEDLINE | ID: mdl-33096476
BACKGROUND: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality world wide and constitutes the third most common malignancy in women. The RAIDs consortium (http://www.raids-fp7.eu/) conducted a prospective European study [BioRAIDs (NCT02428842)] with the objective to stratify CC patients for innovative treatments. A "metagene" of genomic markers in the PI3K pathway and epigenetic regulators had been previously associated with poor outcome [2]. METHODS: To detect new, more specific, targets for treatment of patients who resist standard chemo-radiation, a high-dimensional Cox model was applied to define dominant molecular variants, copy number variations, and reverse phase protein arrays (RPPA). FINDINGS: Survival analysis on 89 patients with all omics data available, suggested loss-of-function (LOF) or activating molecular alterations in nine genes to be candidate biomarkers for worse prognosis in patients treated by chemo-radiation while LOF of ATRX, MED13 as well as CASP8 were associated with better prognosis. When protein expression data by RPPA were factored in, the supposedly low molecular weight and nuclear form, of beta-catenin, phosphorylated in Ser552 (pß-Cat552), ranked highest for good prognosis, while pß-Cat675 was associated with worse prognosis. INTERPRETATION: These findings call for molecularly targeted treatments involving p53, Wnt pathway, PI3K pathway, and epigenetic regulator genes. Pß-Cat552 and pß-Cat675 may be useful biomarkers to predict outcome to chemo-radiation, which targets the DNA repair axis. FUNDING: European Union's Seventh Program for research, technological development and demonstration (agreement N°304,810), the Fondation ARC pour la recherche contre le cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Marcadores Genéticos / Neoplasias do Colo do Útero / Beta Catenina Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biomarcadores Tumorais / Marcadores Genéticos / Neoplasias do Colo do Útero / Beta Catenina Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article