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Proteomic profiling identifies outcome-predictive markers in patients with peripheral T-cell lymphoma, not otherwise specified by Maja Ludvigsen, Martin Bjerregård Pedersen, Kristina Lystlund Lauridsen, Tim Svenstrup Poulsen, Stephen Jacques Hamilton-Dutoit, Søren Besenbacher, Knud Bendix, Michael Boe Møller, Peter Nørgaard, Francesco d’Amore, and Bent Honoré BloodAdv Volume 2(19): October 9, 2018 © 2018 by The American Society of Hematology
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Maja Ludvigsen et al. Blood Adv 2018;2:2533-2542
© 2018 by The American Society of Hematology
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Study design and flowchart of the analyses.
Study design and flowchart of the analyses. Initially proteins in all samples were separated using 2D-PAGE. PTCL-NOS cases were dichotomized according to PCA and clinical outcome in C1 vs C2 and G1 vs G2, respectively. Differential protein expressions were compared in: analysis A, PTCL-NOS (n = 18) vs N (n = 8); analysis B, PCA defined clusters C1 (n = 7) vs C2 (n = 11); and analysis C, PTCL-NOS patients with primary refractory disease (G1) with survival <100 days (n = 4) vs PTCL-NOS patients with chemosensitive disease and survival >2 years (G2) (n = 8). In the latter analysis, 6 cases were omitted for failing to fulfill the defined criteria of treatment response. Spots with ≥twofold differential expression were excised, and protein identifications were performed by liquid chromatography tandem mass spectrometry (LC-MS/MS). ENO1, TPI1, and ALDH2 protein expression was assessed in a larger cohort of PTCL-NOS patients (n = 87) by IHC and digitally quantified using digital image analysis on TMA cores. ALDH2, aldehyde dehydrogenase 2, mitochondrial; CR, complete remission; N, nonneoplastic tissue; TPI1, triosephosphate isomerase. Maja Ludvigsen et al. Blood Adv 2018;2: © 2018 by The American Society of Hematology
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PCA cluster analysis. PCA cluster analysis. (A) PCA analysis showing distinct separation of PTCL-NOS tumors from nonneoplastic lymphoid reference tissue and additional clustering within PTCL-NOS in distinct groups (ie, C1 and C2). (B) Hierachical clustering showing distinct protein profiles between N, C1, and C2. With this analysis, 1 of the C2 patients clustered with the C1 group. Green denotes downregulation, and red denotes upregulation. (C) OS of PTCL-NOS patients according to groups (C1 and C2) identified from cluster analysis. N, nonneoplastic lymphoid tissue. Maja Ludvigsen et al. Blood Adv 2018;2: © 2018 by The American Society of Hematology
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Immunohistochemical evaluation of putative predictive markers and outcome in PTCL-NOS patients.
Immunohistochemical evaluation of putative predictive markers and outcome in PTCL-NOS patients. Representative images showing high and low expression of ENO1 (A-B), ALDH2 (D-E), and TPI1 (G-H) by IHC are shown in PTCL-NOS tissue. OS curves for the patients according to marker expression (C,F,I).Original magnification ×10. Maja Ludvigsen et al. Blood Adv 2018;2: © 2018 by The American Society of Hematology
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