Gene Expression Pattern of ESPL1, PTTG1 and PTTG1IP Can Potentially Predict Response to TKI First-Line Treatment of Patients with Newly Diagnosed CML
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. Molecular Response in Treatment of Chronic Myeloid Leukemia
1.2. ESPL1/Separase, PTTG1/Securin and PTTG1IP/Securin Interacting Protein
2. Materials and Methods
2.1. Patients and Controls
2.2. Sample Preparation and Quantification of BCR::ABL1
2.3. Relative Quantification of ESPL1, PTTG1, PTTG1IP Transcript Levels
2.4. Statistics
3. Results
3.1. Relative Gene Expression of ESPL1, PTTG1 and PTTG1IP
3.2. Distance Analysis for Risk Stratification
3.3. Leukocyte Count at ID Differs between R and NR Cohort
3.4. ESPL1, PTTG1 and PTTG1IP Gene Expression Levels in R Cohort Correlate with Time until Achievement of MMR
3.5. Leukocyte Counts at Time of ID, BCR::ABL1 Quotients and TKI Therapy Correlate with Time until Achievement of MMR
3.6. Predictable NR Display Lower ESPL1 and PTTG1IP Transcript Levels Compared to Corresponding R
3.7. NR and R Cohort Assignment Concurs with Rate of BCR::ABL1 Decline after 3 Months of TKI Treatment
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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ANOVA | ESPL1 | PTTG1 | PTTG1IP |
---|---|---|---|
global | p < 0.0001 | p = 0.0036 | p = 0.1736 |
controls vs. NR * | p < 0.0001 | p = 0.0127 | - |
controls vs. R * | p = 0.0061 | p = 0.0167 | - |
NR vs. R * | p = 0.3910 | p = 0.9998 | - |
Sample No. | Sensitivity | Specificity | Sum | Cut-Off |
---|---|---|---|---|
1 | 1 | 0 | 1 | 0.549594 |
2 | 1 | 0.021739 | 1.021739 | 0.633119 |
3 | 1 | 0.043478 | 1.043478 | 0.750284 |
4 | 1 | 0.065217 | 1.065217 | 0.773095 |
5 | 1 | 0.086957 | 1.086957 | 0.951466 |
6 | 1 | 0.108696 | 1.108696 | 0.980357 |
7 | 0.980392 | 0.108696 | 1.089088 | 1.150964 |
8 | 0.960784 | 0.108696 | 1.06948 | 1.156968 |
9 | 0.960784 | 0.130435 | 1.091219 | 1.162309 |
10 | 0.960784 | 0.152174 | 1.112958 | 1.17719 |
11 | 0.941176 | 0.152174 | 1.09335 | 1.244523 |
12 | 0.921569 | 0.152174 | 1.073743 | 1.335997 |
13 | 0.901961 | 0.152174 | 1.054135 | 1.355251 |
14 | 0.882353 | 0.152174 | 1.034527 | 1.441234 |
15 | 0.882353 | 0.173913 | 1.056266 | 1.488975 |
16 | 0.862745 | 0.173913 | 1.036658 | 1.534161 |
17 | 0.843137 | 0.173913 | 1.01705 | 1.601827 |
18 | 0.823529 | 0.173913 | 0.997442 | 1.605338 |
19 | 0.823529 | 0.195652 | 1.019182 | 1.61878 |
20 | 0.823529 | 0.217391 | 1.040921 | 1.637496 |
21 | 0.803922 | 0.217391 | 1.021313 | 1.647798 |
22 | 0.803922 | 0.23913 | 1.043052 | 1.652854 |
23 | 0.784314 | 0.23913 | 1.023444 | 1.708054 |
24 | 0.764706 | 0.23913 | 1.003836 | 1.757046 |
25 | 0.764706 | 0.26087 | 1.025575 | 1.793212 |
26 | 0.745098 | 0.26087 | 1.005968 | 1.793669 |
27 | 0.72549 | 0.26087 | 0.98636 | 1.79974 |
28 | 0.705882 | 0.26087 | 0.966752 | 1.810044 |
29 | 0.705882 | 0.282609 | 0.988491 | 1.840533 |
30 | 0.686275 | 0.282609 | 0.968883 | 1.864345 |
31 | 0.686275 | 0.304348 | 0.990622 | 1.95028 |
32 | 0.666667 | 0.304348 | 0.971014 | 1.964042 |
33 | 0.666667 | 0.326087 | 0.992754 | 2.015026 |
34 | 0.666667 | 0.347826 | 1.014493 | 2.039745 |
35 | 0.647059 | 0.347826 | 0.994885 | 2.042153 |
36 | 0.627451 | 0.347826 | 0.975277 | 2.05187 |
37 | 0.627451 | 0.369565 | 0.997016 | 2.057197 |
38 | 0.607843 | 0.369565 | 0.977408 | 2.069368 |
39 | 0.607843 | 0.391304 | 0.999147 | 2.085874 |
40 | 0.588235 | 0.391304 | 0.97954 | 2.096926 |
41 | 0.568627 | 0.391304 | 0.959932 | 2.122027 |
42 | 0.568627 | 0.413043 | 0.981671 | 2.124711 |
43 | 0.568627 | 0.434783 | 1.00341 | 2.180675 |
44 | 0.568627 | 0.456522 | 1.025149 | 2.189591 |
45 | 0.54902 | 0.456522 | 1.005541 | 2.195555 |
46 | 0.54902 | 0.478261 | 1.02728 | 2.20937 |
47 | 0.54902 | 0.5 | 1.04902 | 2.277969 |
48 | 0.54902 | 0.521739 | 1.070759 | 2.283053 |
49 | 0.54902 | 0.543478 | 1.092498 | 2.316287 |
50 | 0.54902 | 0.565217 | 1.114237 | 2.358355 |
51 | 0.54902 | 0.586957 | 1.135976 | 2.363681 |
52 | 0.529412 | 0.586957 | 1.116368 | 2.376338 |
53 | 0.509804 | 0.586957 | 1.09676 | 2.405917 |
54 | 0.509804 | 0.608696 | 1.1185 | 2.429324 |
55 | 0.509804 | 0.630435 | 1.140239 | 2.444764 |
56 | 0.509804 | 0.652174 | 1.161978 | 2.456408 |
57 | 0.509804 | 0.673913 | 1.183717 | 2.465865 |
58 | 0.490196 | 0.673913 | 1.164109 | 2.469809 |
59 | 0.470588 | 0.673913 | 1.144501 | 2.516639 |
60 | 0.45098 | 0.673913 | 1.124893 | 2.564055 |
61 | 0.45098 | 0.695652 | 1.146633 | 2.565945 |
62 | 0.45098 | 0.717391 | 1.168372 | 2.611456 |
63 | 0.431373 | 0.717391 | 1.148764 | 2.678705 |
64 | 0.431373 | 0.73913 | 1.170503 | 2.710391 |
65 | 0.431373 | 0.76087 | 1.192242 | 2.73141 |
66 | 0.411765 | 0.76087 | 1.172634 | 2.771444 |
67 | 0.392157 | 0.76087 | 1.153026 | 2.799222 |
68 | 0.392157 | 0.782609 | 1.174766 | 2.815116 |
69 | 0.392157 | 0.804348 | 1.196505 | 2.85643 |
70 | 0.392157 | 0.826087 | 1.218244 | 2.860967 |
71 | 0.372549 | 0.826087 | 1.198636 | 2.880366 |
72 * | 0.372549 | 0.847826 | 1.220375 | 3.021803 |
73 | 0.352941 | 0.847826 | 1.200767 | 3.028484 |
74 | 0.333333 | 0.847826 | 1.181159 | 3.061431 |
75 | 0.313725 | 0.847826 | 1.161552 | 3.115181 |
76 | 0.313725 | 0.869565 | 1.183291 | 3.149723 |
77 | 0.313725 | 0.891304 | 1.20503 | 3.156747 |
78 | 0.294118 | 0.891304 | 1.185422 | 3.205288 |
79 | 0.27451 | 0.891304 | 1.165814 | 3.209935 |
80 | 0.27451 | 0.913043 | 1.187553 | 3.334363 |
81 | 0.254902 | 0.913043 | 1.167945 | 3.347152 |
82 | 0.235294 | 0.913043 | 1.148338 | 3.452303 |
83 | 0.235294 | 0.934783 | 1.170077 | 3.481048 |
84 | 0.215686 | 0.934783 | 1.150469 | 3.481381 |
85 | 0.215686 | 0.956522 | 1.172208 | 3.547112 |
86 | 0.215686 | 0.978261 | 1.193947 | 3.579134 |
87 | 0.196078 | 0.978261 | 1.174339 | 3.624489 |
88 | 0.176471 | 0.978261 | 1.154731 | 3.698418 |
89 | 0.156863 | 0.978261 | 1.135124 | 3.789116 |
90 | 0.137255 | 0.978261 | 1.115516 | 3.802186 |
91 | 0.117647 | 0.978261 | 1.095908 | 4.781442 |
92 | 0.098039 | 0.978261 | 1.0763 | 5.099709 |
93 ** | 0.098039 | 1 | 1.098039 | 5.917999 |
94 | 0.078431 | 1 | 1.078431 | 6.435286 |
95 | 0.058824 | 1 | 1.058824 | 8.635014 |
96 | 0.039216 | 1 | 1.039216 | 9.944185 |
97 | 0.019608 | 1 | 1.019608 | 10.28212 |
Parameter | Test | p-Value |
---|---|---|
Age | t-test | 0.873 |
Sex | Chi2-test | 0.990 |
Time until achievement of MMR | U-test | <0.001 |
Leukocyte count at ID | U-test | 0.018 |
BCR::ABL1 gene fusion type | Fisher-test | 0.487 |
BCR::ABL1 quotient | U-test | 0.067 |
BCR::ABL1 quotient IS * | U-test | 0.173 |
Proportion of imatinib to administered TKIs | U-test | 0.007 |
NR | R | p-Values | |
---|---|---|---|
Distance * | 8.42 ± 1.99 | 2.47 ± 0.18 | 0.0028 |
ΔCt ** ESPL1 | 8.48 ± 1.17 | 6.52 ± 0.25 | 0.018 |
ΔCt ** PTTG1 | 6.26 ± 3.26 | 3.97 ± 0.57 | 0.1936 |
ΔCt ** PTTG1IP | 7.89 ± 3.82 | 1.32 ± 0.84 | 0.0168 |
Leukocytes (cells/μL) | 19760 ± 23302 | 7180 ± 2097 | 0.2946 |
BCR::ABL1 quotient (%) | 14.29 ± 10.16 | 0.88 ± 1.10 | 0.0414 |
NR (n = 49) | R (n = 45) | |||
---|---|---|---|---|
Halving Time (Days) * 3 M (n = 40) | Doubling Time (Days) * 3 M (n = 9) | Halving Time (Days) * 3 M (n = 41) | Doubling Time (Days) * 3 M (n = 4) | |
Mean | 86 ± 87 | 72 ± 55 | 51 ± 18 | 268 ± 280 |
Median | 55 | 52 | 45 | 223 |
Min | 45 | 11 | 45 | 26 |
Max | 541 | 186 | 133 | 600 |
Range | 496 | 175 | 88 | 574 |
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Christiani, E.; Naumann, N.; Weiss, C.; Spiess, B.; Kleiner, H.; Fabarius, A.; Hofmann, W.-K.; Saussele, S.; Seifarth, W. Gene Expression Pattern of ESPL1, PTTG1 and PTTG1IP Can Potentially Predict Response to TKI First-Line Treatment of Patients with Newly Diagnosed CML. Cancers 2023, 15, 2652. https://doi.org/10.3390/cancers15092652
Christiani E, Naumann N, Weiss C, Spiess B, Kleiner H, Fabarius A, Hofmann W-K, Saussele S, Seifarth W. Gene Expression Pattern of ESPL1, PTTG1 and PTTG1IP Can Potentially Predict Response to TKI First-Line Treatment of Patients with Newly Diagnosed CML. Cancers. 2023; 15(9):2652. https://doi.org/10.3390/cancers15092652
Chicago/Turabian StyleChristiani, Eva, Nicole Naumann, Christel Weiss, Birgit Spiess, Helga Kleiner, Alice Fabarius, Wolf-Karsten Hofmann, Susanne Saussele, and Wolfgang Seifarth. 2023. "Gene Expression Pattern of ESPL1, PTTG1 and PTTG1IP Can Potentially Predict Response to TKI First-Line Treatment of Patients with Newly Diagnosed CML" Cancers 15, no. 9: 2652. https://doi.org/10.3390/cancers15092652