Low expression of pro-apoptotic proteins Bax, Bak and Smac indicates prolonged progression-free survival in chemotherapy-treated metastatic melanoma
| Autor: | Markus Rehm, Mairin Rafferty, Peter Dynoodt, Elodie Hirschenhahn, Joost van den Oord, William M. Gallagher, Ciaran de Chaumont, Cristiano Guttà, Claudia Aura, Arman Rahman, Madhuri Warren, Jesuchristopher Joseph, Emilie M. Charles, Jasper Wouters |
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| Rok vydání: | 2020 |
| Předmět: |
SMAC/DIABLO
Male Cancer Research Skin Neoplasms Time Factors medicine.medical_treatment Pattern Recognition Automated Prognostic markers 0302 clinical medicine Medicine Melanoma bcl-2-Associated X Protein 0303 health sciences Tissue microarray lcsh:Cytology Middle Aged Immunohistochemistry Progression-Free Survival 3. Good health XIAP bcl-2 Homologous Antagonist-Killer Protein 030220 oncology & carcinogenesis GROWTH Female biological phenomena cell phenomena and immunity Life Sciences & Biomedicine PATIENT PROGNOSIS Immunology Down-Regulation Antineoplastic Agents Article Mitochondrial Proteins 03 medical and health sciences Cellular and Molecular Neuroscience Predictive Value of Tests Image Interpretation Computer-Assisted MANAGEMENT Biomarkers Tumor Humans CANCER PATIENTS Progression-free survival lcsh:QH573-671 CLINICAL-SIGNIFICANCE BCL-2 EXPRESSION DACARBAZINE Aged 030304 developmental biology Chemotherapy Science & Technology business.industry Gene Expression Profiling Cell Biology medicine.disease PHASE-III Tissue Array Analysis Apoptosis CELLS Cancer cell Cancer research Apoptosis Regulatory Proteins business |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 2, Pp 1-12 (2020) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-020-2309-3 |
| Popis: | Despite the introduction of novel targeted therapies, chemotherapy still remains the primary treatment for metastatic melanoma in poorly funded healthcare environments or in case of disease relapse, with no reliable molecular markers for progression-free survival (PFS) available. As chemotherapy primarily eliminates cancer cells by apoptosis, we here evaluated if the expression of key apoptosis regulators (Bax, Bak, Bcl-2, Bcl-xL, Smac, Procaspase-9, Apaf-1, Procaspase-3 and XIAP) allows prognosticating PFS in stage III/IV melanoma patients. Following antibody validation, marker expression was determined by automated and manual scoring of immunohistochemically stained tissue microarrays (TMAs) constructed from treatment-naive metastatic melanoma biopsies. Interestingly and counter-intuitively, low expression of the pro-apoptotic proteins Bax, Bak and Smac indicated better prognosis (log-rank p 12 months) on a case-by-case basis (area under the receiver operating characteristic curve (ROC AUC) = 0.79). Taken together, our results therefore suggest that Bax, Bak and Smac jointly define a signature with potential clinical utility in chemotherapy-treated metastatic melanoma. ispartof: CELL DEATH & DISEASE vol:11 issue:2 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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