Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Samples
2.2. Sequencing and Mutation Analysis
2.3. Tissue Microarray Construction
2.4. Immunohistochemistry and Scoring
2.5. Statistical Analysis
3. Results
3.1. EZH1 and EZH2 Mutations
3.2. EZH1, EZH,2 and H3K27me3 Protein Expression Levels in T-Cell Lymphomas
3.3. Associations between EZH1, EZH2 and H3K27me3 Protein Expression
3.4. Associations between EZH1, EZH2 and H3K27me3 Protein Expression and Clinicopathological Characteristics
3.5. Divergent Effects of EZH1 and EZH2/H3K27me3 Protein Expression on Patient Prognosis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | MEITL n = 33 | |
---|---|---|
n (%) | ||
Sex | Female | 16 (49) |
Male | 12 (36) | |
Not evaluable | 5 (15) | |
Age | Median (years) (range) | 62 (38–92) |
Histopathology | CD3positive | 33 (100) |
CD4negative | 31(94) | |
CD8positive | 27 (82) | |
CD58positive | 31 (94) | |
T-cell Receptor | αβpositive | 10 (30) |
γδpositive | 9 (27) | |
Not evaluable | 14 (42) |
Characteristics | T-NHL n = 46 | Nodal T-NHL n = 34 | |
---|---|---|---|
n (%) | n (%) | ||
Sex | Female | 15 (33) | 12 (35) |
Male | 31 (67) | 22 (65) | |
Age | Median (years) (range) | 64.1 (36–92) | 64.4 (51–92) |
B symptoms | Absent | 27 (59) | 20 (59) |
Present | 18 (39) | 14 (41) | |
Not evaluable | 1 (2) | 0 (0) | |
Bone marrow involvement | Absent | 32 (70) | 25 (74) |
Present | 10 (22) | 7 (21) | |
Not evaluable | 4 (9) | 2 (6) | |
Ann Arbor stage | Stages I and II | 8 (17) | 6 (18) |
Stages III and IV | 28 (61) | 25 (74) | |
Not evaluable | 10(22) | 3 (9) | |
IPI | 0–2 | 18 (39) | 15 (44) |
3–5 | 19 (41) | 17 (50) | |
Not evaluable | 9 (20) | 2 (6) | |
ECOG | 0–1 | 20 (43) | 16 (47) |
2–5 | 6 (13) | 5 (15) | |
Not evaluable | 20 (43) | 13 (38) | |
WBC | Normal | 13 (28) | 8 (24) |
Upper limit of normal | 11 (24) | 7 (21) | |
Not evaluable | 22 (48) | 19 (56) | |
LDH | Normal | 6 (13) | 2 (6) |
Upper limit of normal | 19 (41) | 17 (50) | |
Not evaluable | 21 (46) | 15 (44) | |
Ki-67 expression | <65% | 16 (35) | 12 (35) |
≥65% | 14 (30) | 10 (29) | |
Not evaluable | 19 (35) | 12 (35) | |
Relapse | Absent | 23 (50) | 14 (41) |
Present | 23 (50) | 20 (59) | |
First-line treatment | (R)-CHO(E)P | 37 (80) | 33 (97) |
Others | 9 (20) | 1 (1) |
T-NHL (n = 41) | Nodal T-NHL (n = 30) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Variable | Categories | HR | 95% CI | p-Value | HR | 95% CI | p-Value | ||
LL | UL | LL | UL | ||||||
Overall Survival | |||||||||
Sex | female vs. male | 3.816 | 0.990 | 14.699 | 0.052 | 2.900 | 0.462 | 18.198 | 0.256 |
Age in years | 1.053 | 0.998 | 1.111 | 0.059 | 1.070 | 0.979 | 1.171 | 0.137 | |
Ann Arbor stage | III–IV vs. I–II | 0.148 | 0.021 | 1.042 | 0.055 | ||||
B Symptoms | present vs. absent | 1.182 | 0.411 | 3.397 | 0.756 | 1.066 | 0.166 | 6.822 | 0.947 |
Bone marrow involvement | present vs. absent | 2.148 | 0.614 | 7.513 | 0.232 | 1.312 | 0.220 | 7.814 | 0.766 |
EZH1 expression | high vs. low | 0.183 | 0.044 | 0.767 | 0.020 | 0.085 | 0.008 | 0.859 | 0.037 |
EZH2 expression | high vs. low | 8.245 | 1.898 | 35.826 | 0.005 | 28.398 | 2.166 | 372.334 | 0.011 |
H3K27me3 expression | high vs. low | 2.322 | 0.688 | 7.836 | 0.175 | 3.500 | 0.735 | 16.652 | 0.115 |
Progression-Free Survival | |||||||||
Sex | female vs. male | 1.607 | 0.630 | 4.097 | 0.321 | 0.959 | 0.289 | 3.179 | 0.945 |
Age in years | 1.008 | 0.966 | 1.051 | 0.728 | 0.987 | 0.932 | 1.046 | 0.660 | |
Ann Arbor stage | III–IV vs. I–II | 0.933 | 0.249 | 3.495 | 0.918 | ||||
B Symptoms | present vs. absent | 1.299 | 0.512 | 3.298 | 0.582 | 0.888 | 0.250 | 3.159 | 0.855 |
Bone marrow involvement | present vs. absent | 4.621 | 1.706 | 12.515 | 0.003 | 3.750 | 1.252 | 11.231 | 0.018 |
EZH1 expression | high vs. low | 0.668 | 0.246 | 1.814 | 0.428 | 0.391 | 0.104 | 1.471 | 0.165 |
EZH2 expression | high vs. low | 3.754 | 1.233 | 11.426 | 0.020 | 5.147 | 1.472 | 17.998 | 0.010 |
H3K27me3 expression | high vs. low | 1.326 | 0.546 | 3.218 | 0.533 | 1.537 | 0.469 | 5.038 | 0.478 |
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Schümann, F.L.; Groß, E.; Bauer, M.; Rohde, C.; Sandmann, S.; Terziev, D.; Müller, L.P.; Posern, G.; Wienke, A.; Fend, F.; Hansmann, M.-L.; Klapper, W.; Rosenwald, A.; Stein, H.; Dugas, M.; Müller-Tidow, C.; Wickenhauser, C.; Binder, M.; Weber, T. Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas. Biomedicines 2021, 9, 1842. https://doi.org/10.3390/biomedicines9121842
Schümann FL, Groß E, Bauer M, Rohde C, Sandmann S, Terziev D, Müller LP, Posern G, Wienke A, Fend F, Hansmann M-L, Klapper W, Rosenwald A, Stein H, Dugas M, Müller-Tidow C, Wickenhauser C, Binder M, Weber T. Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas. Biomedicines. 2021; 9(12):1842. https://doi.org/10.3390/biomedicines9121842
Chicago/Turabian StyleSchümann, Franziska Lea, Elisabeth Groß, Marcus Bauer, Christian Rohde, Sarah Sandmann, Denis Terziev, Lutz P. Müller, Guido Posern, Andreas Wienke, Falko Fend, Martin-Leo Hansmann, Wolfram Klapper, Andreas Rosenwald, Harald Stein, Martin Dugas, Carsten Müller-Tidow, Claudia Wickenhauser, Mascha Binder, and Thomas Weber. 2021. "Divergent Effects of EZH1 and EZH2 Protein Expression on the Prognosis of Patients with T-Cell Lymphomas" Biomedicines 9, no. 12: 1842. https://doi.org/10.3390/biomedicines9121842