Genetic markers and phosphoprotein forms of beta-catenin pβ-Cat552 and pβ-Cat675 are prognostic biomarkers of cervical cancer
| العنوان: | Genetic markers and phosphoprotein forms of beta-catenin pβ-Cat552 and pβ-Cat675 are prognostic biomarkers of cervical cancer |
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| المؤلفون: | Elodie Girard, Suzy Scholl, Pierre Gestraud, Els M.J.J. Berns, Virginie Fourchotte, Maud Kamal, Aurélien Latouche, Charlotte Lecerf, Attila Kereszt, Sergio Roman Roman, Balazs Balint, Gemma Kenter, Fabrice Lecuru, Anne Floquet, Anne de la Rochefordiere, Marina Popovic, Heiko von der Leyen, Roman Rouzier, Leanne de Koning, Jonas Béal, Vincent Puard, Charlotte Ngo |
| المساهمون: | Medical Oncology, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), AII - Cancer immunology, Amsterdam Reproduction & Development (AR&D), CCA - Imaging and biomarkers, Obstetrics and gynaecology |
| المصدر: | EBioMedicine, 61:103049. Elsevier Scholl, S M, Beal, J, de Koning, L, Girard, E, Popovic, M, de la Rochefordière, A, Lecuru, F, Fourchotte, V, Ngo, C, Floquet, A, Berns, E MJJ, Kenter, G, Gestraud, P, von der Leyen, H, Lecerf, C, Puard, V, Roman, S R, Latouche, A, Kereszt, A, Balint, B, Rouzier, R & Kamal, M 2020, ' Genetic markers and phosphoprotein forms of beta-catenin pβ-Cat552 and pβ-Cat675 are prognostic biomarkers of cervical cancer ', EBioMedicine, vol. 61, 103049 . https://doi.org/10.1016/j.ebiom.2020.103049Test EBioMedicine EBioMedicine, Elsevier, 2020, 61, pp.103049-. ⟨10.1016/j.ebiom.2020.103049⟩ EBioMedicine, 61:103049. Elsevier BV EBioMedicine, Vol 61, Iss, Pp 103049-(2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, [SDV]Life Sciences [q-bio], lcsh:Medicine, Uterine Cervical Neoplasms, SCC, squamous cell carcinoma, LMW, low molecular weight, 0302 clinical medicine, Recurrence, Medicine, Copy-number variation, Phosphorylation, beta Catenin, media_common, lcsh:R5-920, LOF, Loss-of-function, WES, Whole exome sequencing, RPPA, Reverse phase protein array, Reverse phase protein lysate microarray, General Medicine, TCF4, transcription factor 4, Prognosis, HPV, Human papillomavirus, 3. Good health, 030220 oncology & carcinogenesis, Female, Disease Susceptibility, lcsh:Medicine (General), Research Paper, Genetic Markers, medicine.medical_specialty, DNA Copy Number Variations, Abbreviations:CC, Cervical cancer, CNV, copy number variation, Beta-catenin pβ-cat552 and pβ-cat675, Molecular and protein biomarkers for chemo-radiation efficiency, Malignancy, General Biochemistry, Genetics and Molecular Biology, Genetic Heterogeneity, 03 medical and health sciences, SDG 3 - Good Health and Well-being, PFS, Progression-free survival, Internal medicine, Exome Sequencing, Biomarkers, Tumor, Humans, media_common.cataloged_instance, Epigenetics, European union, Survival analysis, ATRX, Neoplasm Staging, business.industry, lcsh:R, Computational Biology, Cancer, Phosphoproteins, medicine.disease, Molecular landscape, 030104 developmental biology, Mutation, Cervical cancer, business |
| الوصف: | 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.euTest/ ) 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 (pβ-Cat552), ranked highest for good prognosis, while pβ-Cat675 was associated with worse prognosis. INTERPRETATION These findings call for molecularly targeted treatments involving p53, Wnt pathway, PI3K pathway, and epigenetic regulator genes. Pβ-Cat552 and pβ-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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2352-3964 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::916d8985f7a52722fd1f9b726275820aTest http://www.scopus.com/inward/record.url?scp=85092895744&partnerID=8YFLogxKTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....916d8985f7a52722fd1f9b726275820a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523964 |
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