Proteomic profiling identifies outcome-predictive markers in patients with peripheral T-cell lymphoma, not otherwise specified
| Autor: | Knud Bendix, Tim Svenstrup Poulsen, Bent Honoré, Søren Besenbacher, Martin Bjerregård Pedersen, Stephen Hamilton-Dutoit, Francesco d'Amore, Kristina Lystlund Lauridsen, Michael Boe Møller, Maja Ludvigsen, Peter Nørgaard |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Proteomics 0301 basic medicine Proteome Lymphoid Tissue Peripheral T-cell lymphoma not otherwise specified Biology Pathogenesis 03 medical and health sciences 0302 clinical medicine Tandem Mass Spectrometry Biomarkers Tumor medicine Humans Lymphoid Neoplasia Proteomic Profiling Aldehyde Dehydrogenase Mitochondrial Tumor Suppressor Proteins Not Otherwise Specified Computational Biology Lymphoma T-Cell Peripheral Hematology Prognosis medicine.disease Lymphoma DNA-Binding Proteins 030104 developmental biology Lymphatic system Phosphopyruvate Hydratase 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Female human activities Chromatography Liquid |
| Zdroj: | Ludvigsen, M, Bjerregård Pedersen, M, Lystlund Lauridsen, K, Svenstrup Poulsen, T, Hamilton-Dutoit, S J, Besenbacher, S, Bendix, K, Møller, M B, Nørgaard, P, d'Amore, F & Honoré, B 2018, ' Proteomic profiling identifies outcome-predictive markers in patients with peripheral T-cell lymphoma, not otherwise specified ', Blood Advances, vol. 2, no. 19, pp. 2533-2542 . https://doi.org/10.1182/bloodadvances.2018019893 |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2018019893 |
| Popis: | Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) constitutes a heterogeneous category of lymphomas, which do not fit into any of the specifically defined T-cell lymphoma entities. Both the pathogenesis and tumor biology in PTCL-NOS are poorly understood. Protein expression in pretherapeutic PTCL-NOS tumors was analyzed by proteomics. Differentially expressed proteins were compared in 3 distinct scenarios: (A) PTCL-NOS tumor tissue (n = 18) vs benign lymphoid tissue (n = 8), (B) clusters defined by principal component analysis (PCA), and (C) tumors from patients with chemosensitive vs refractory PTCL-NOS. Selected differentially expressed proteins identified by proteomics were correlated with clinico-pathological features and outcome in a larger cohort of patients with PTCL-NOS (n = 87) by immunohistochemistry (IHC). Most proteins with altered expression were identified comparing PTCL-NOS vs benign lymphoid tissue. PCA of the protein profile defined 3 distinct clusters. All benign samples clustered together, whereas PTCL-NOS tumors separated into 2 clusters with different patient overall survival rates (P = .001). Differentially expressed proteins reflected large biological diversity among PTCL-NOS, particularly associated with alterations of “immunological” pathways. The 2 PTCL-NOS subclusters defined by PCA showed disturbance of “stress-related” and “protein metabolic” pathways. α-Enolase 1 (ENO1) was found differentially expressed in all 3 analyses, and high intratumoral ENO1 expression evaluated by IHC correlated with poor outcome (hazard ratio, 2.09; 95% confidence interval, 1.17-3.73; P = .013). High expression of triosephosphate isomerase (TPI1) also showed a tendency to correlate with poor survival (P = .057). In conclusion, proteomic profiling of PTCL-NOS provided evidence of markedly altered protein expression and identified ENO1 as a novel potential prognostic marker. |
| Databáze: | OpenAIRE |
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