Qualitative and Quantitative Requirements for Assessing Prognostic Markers in Prostate Cancer
Abstract
:1. Introduction
2. Experimental Section
Parameter | No. of patients (%) | |
---|---|---|
Study cohort on TMA | Biochemical relapse among categories | |
(n = 12,427) | ||
Follow-up (mo) | ||
n | 11,665 (93.9%) | 2769 (23.7%) |
Mean | 48.9 | - |
Median | 36.4 | - |
Age (y) | ||
≤50 | 334 (2.7%) | 81 (24.3%) |
51–59 | 3061 (24.8%) | 705 (23%) |
60–69 | 7188 (58.2%) | 1610 (22.4%) |
≥70 | 1761 (14.3%) | 370 (21%) |
Pretreatment prostate specific antigen (PSA) (ng/mL) | ||
<4 | 1585 (12.9%) | 242 (15.3%) |
4–10 | 7480 (60.9%) | 1355 (18.1%) |
10–20 | 2412 (19.6%) | 737 (30.6%) |
>20 | 812 (6.6%) | 397 (48.9%) |
pT category (AJCC 2002) | ||
pT2 | 8187 (66.2%) | 1095 (13.4%) |
pT3a | 2660 (21.5%) | 817 (30.7%) |
pT3b | 1465 (11.8%) | 796 (54.3%) |
pT4 | 63 (0.5%) | 51 (81%) |
Gleason grade | ||
≤3 + 3 | 2983 (24.1%) | 368 (12.3%) |
3 + 4 | 6945 (56.2%) | 1289 (18.6%) |
4 + 3 | 1848 (15%) | 788 (42.6%) |
≥4 + 4 | 584 (4.7%) | 311 (53.3%) |
pN category | ||
pN0 | 6970 (91%) | 1636 (23.5%) |
pN+ | 693 (9%) | 393 (56.7%) |
Surgical margin | ||
Negative | 9990 (81.9%) | 1848 (18.5%) |
Positive | 2211 (18.1%) | 853 (38.6%) |
3. Results and Discussion
3.1. Impact of the Tissue Quality
Marker | Low quality tissue | Number of analyzed tissue spots | Association strength | |||
---|---|---|---|---|---|---|
1600 | 3200 | 6400 | 10,000 | |||
Marker #32 | included | 0.1039 | 0.5243 | 0.1879 | 0.0952 | No association |
excluded | 0.9431 | 0.6612 | 0.7653 | 0.6515 | ||
Marker #13 | included | 0.0112 | <0.0001 | <0.0001 | <0.0001 | Weak |
excluded | 0.012 | 0.0004 | <0.0001 | <0.0001 | ||
Marker #12 (MTC02) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Weak |
excluded | 0.0238 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #31 | included | 0.1307 | 0.0091 | <0.0001 | <0.0001 | Weak |
excluded | 0.2414 | 0.0031 | <0.0001 | <0.0001 | ||
Marker #37 | included | 0.0017 | <0.0001 | <0.0001 | <0.0001 | Weak |
excluded | 0.1159 | 0.0012 | 0.0008 | <0.0001 | ||
Marker #7 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #10 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #2 (CD10) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #21 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #27 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #39 (p53) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #4 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker#3 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #5 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #33 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #16 (NBS1) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #18 (AR) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #22 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #24 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #23 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #36 (KPNA2) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #35 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #30 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Moderate |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #6 (FOXP2) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #8 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #9 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #11 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #14 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #15 (LPCAT) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #19 (RBM3) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #26 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #26 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #25 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #29 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Strong |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #1 (CD147) | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Inverse |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #17 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Inverse |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #20 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Inverse |
excluded | 0.0004 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #34 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Inverse |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 | ||
Marker #38 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 | Inverse |
excluded | <0.0001 | <0.0001 | <0.0001 | <0.0001 |
Marker | Low quality tissue | Number of analyzed tissue spots | |||
---|---|---|---|---|---|
1600 | 3200 | 6400 | 10,000 | ||
#2 (CD10) | included | 0.0937 | 0.0006 | <0.0001 | <0.0001 |
excluded | 0.1215 | 0.0005 | <0.0001 | <0.0001 | |
#3 | included | 0.0761 | 0.0946 | 0.0595 | 0.0037 |
excluded | 0.1146 | 0.0761 | 0.0385 | 0.0043 | |
#4 | included | 0.0810 | 0.1082 | 0.0151 | <0.0001 |
excluded | 0.1059 | 0.0810 | 0.0060 | <0.0001 | |
#18 (AR) | included | 0.0082 | 0.0206 | 0.0006 | <0.0001 |
excluded | 0.0197 | 0.0082 | 0.0003 | <0.0001 | |
#35 | included | <0.0001 | <0.0001 | <0.0001 | <0.0001 |
excluded | 0.0230 | <0.0001 | <0.0001 | <0.0001 |
3.2. Impact of the Sample Size
Marker | n analy-zable | Number of analyzed tissue spots | Marker Power | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
50 | 100 | 200 | 400 | 800 | 1600 | 3200 | 6400 | 12,427 | |||
Marker #1 (CD147) | 7605 | 0.2417 | 0.4218 | 0.4550 | 0.4984 | 0.5396 | 0.3539 | 0.3428 | 0.0379 | 0.0019 | weak |
Marker #4 | 8025 | 0.0863 | 0.0998 | 0.9252 | 0.4330 | 0.4648 | 0.5781 | 0.0571 | 0.0666 | 0.0002 | weak |
Marker #3 | 7574 | 0.2276 | 0.0720 | 0.0673 | 0.7038 | 0.6825 | 0.0934 | 0.3195 | 0.0351 | 0.0016 | weak |
Marker #5 | 9473 | 0.8553 | 0.2279 | 0.9171 | 0.5532 | 0.1026 | 0.3192 | 0.0797 | 0.0097 | 0.0016 | weak |
Marker #6 (FOXP2) | 8284 | 0.7963 | 0.4436 | 0.0082 | 0.4058 | 0.4309 | 0.0776 | 0.0308 | 0.0011 | <0.0001 | weak |
Marker #7 | 9485 | <0.0001 | 0.4999 | 0.0056 | 0.2196 | 0.0492 | 0.0464 | 0.0796 | 0.0007 | <0.0001 | moderate |
Marker #8 | 8158 | 0.1175 | 0.5066 | 0.7638 | 0.1192 | 0.3055 | 0.0020 | 0.0548 | <0.0001 | <0.0001 | moderate |
Marker #9 | 6494 | 0.0494 | 0.9606 | 0.5709 | 0.1780 | 0.0603 | 0.0421 | 0.0564 | <0.0001 | <0.0001 | moderate |
Marker #33 | 9262 | 0.1088 | 0.2166 | 0.5932 | 0.6114 | 0.0017 | 0.0013 | 0.0105 | <0.0001 | <0.0001 | moderate |
Marker #10 | 9516 | 0.6617 | 0.8651 | 0.0836 | 0.1074 | 0.1415 | 0.0489 | 0.0041 | 0.0034 | <0.0001 | weak |
Marker #2 (CD10) | 8488 | 0.0722 | 0.5977 | 0.6268 | 0.2465 | 0.3409 | 0.5137 | 0.0001 | 0.0062 | 0.0012 | weak |
Marker #11 | 9627 | 0.5518 | 0.1662 | 0.0652 | 0.4009 | 0.5480 | 0.1911 | 0.0009 | 0.0046 | <0.0001 | weak |
Marker #12 (MTC02) | 8407 | 0.4313 | 0.9545 | 0.7656 | 0.9315 | 0.3693 | 0.2517 | 0.0013 | 0.0004 | <0.0001 | weak |
Marker #14 | 8654 | 0.7139 | 0.0146 | 0.6741 | 0.4165 | 0.1473 | 0.4119 | 0.0094 | 0.0002 | <0.0001 | weak |
Marker #16 (NBS1) | 8026 | 0.6506 | 0.0525 | 0.2071 | 0.7379 | 0.8382 | 0.2079 | 0.0004 | 0.0026 | <0.0001 | weak |
Marker #13 | 9875 | 0.8336 | 0.3172 | 0.2557 | 0.6717 | 0.0790 | 0.0962 | 0.0026 | 0.0004 | <0.0001 | weak |
Marker #15 (LPCAT) | 8762 | 0.7141 | 0.1713 | 0.5933 | 0.6978 | 0.2428 | 0.0449 | 0.0020 | 0.0003 | <0.0001 | weak |
Marker #17 | 7275 | 0.7259 | 0.2301 | 0.2169 | 0.3562 | 0.3492 | 0.0661 | 0.0094 | <0.0001 | <0.0001 | moderate |
Marker #18 (AR) | 7856 | 0.4576 | 0.0246 | 0.9451 | 0.6439 | 0.7573 | 0.3058 | <0.0001 | 0.0034 | <0.0001 | moderate |
Marker #20 | 6638 | 0.7489 | 0.7507 | 0.2524 | 0.4930 | 0.9583 | 0.0863 | 0.0001 | <0.0001 | <0.0001 | moderate |
Marker #19 (RBM3) | 8303 | 0.4712 | 0.1035 | 0.4893 | 0.2494 | 0.0134 | 0.0658 | 0.0006 | <0.0001 | <0.0001 | moderate |
Marker #21 | 9643 | 0.8921 | 0.6673 | 0.2718 | 0.0004 | 0.0086 | 0.0170 | <0.0001 | <0.0001 | <0.0001 | moderate |
Marker #28 | 6824 | 0.5465 | 0.0252 | 0.8696 | 0.6919 | 0.2038 | 0.0075 | 0.0026 | <0.0001 | <0.0001 | moderate |
Marker #22 | 7117 | 0.2824 | 0.8367 | 0.5302 | 0.9432 | 0.0591 | 0.0095 | <0.0001 | <0.0001 | <0.0001 | moderate |
Marker #24 | 9756 | 0.5724 | 0.3132 | 0.8763 | 0.6290 | 0.0686 | 0.0016 | <0.0001 | 0.0002 | <0.0001 | moderate |
Marker #23 | 9744 | 0.3087 | 0.0266 | 0.0008 | 0.1771 | 0.3495 | 0.0001 | 0.0004 | <0.0001 | <0.0001 | moderate |
Marker #29 | 9403 | 0.8852 | 0.0612 | 0.1260 | 0.1830 | 0.8574 | 0.0028 | <0.0001 | <0.0001 | <0.0001 | moderate |
Marker #27 | 7588 | 0.0607 | 0.2364 | 0.2661 | 0.0050 | 0.4899 | 0.0001 | <0.0001 | <0.0001 | <0.0001 | moderate |
Marker #26 | 9633 | 0.0169 | 0.5727 | 0.1760 | 0.7661 | 0.0491 | 0.0003 | <0.0001 | <0.0001 | <0.0001 | moderate |
Marker #25 | 7677 | 0.8371 | 0.3814 | 0.7065 | 0.0233 | 0.9297 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | moderate |
Marker #30 | 8174 | 0.3570 | 0.5619 | 0.3006 | 0.0028 | 0.1186 | 0.0002 | <0.0001 | <0.0001 | <0.0001 | strong |
Marker #31 | 10215 | 0.4072 | 0.4062 | 0.2342 | 0.3143 | 0.0040 | 0.0023 | 0.0002 | <0.0001 | <0.0001 | moderate |
Marker #35 | 10216 | 0.8828 | 0.4813 | 0.1523 | 0.1304 | 0.0018 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | strong |
Marker #34 | 7670 | 0.0833 | 0.3010 | 0.2137 | 0.0703 | 0.0001 | 0.0002 | <0.0001 | <0.0001 | <0.0001 | strong |
Marker #37 | 7822 | 0.0044 | 0.0106 | 0.1209 | 0.0247 | 0.0002 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | strong |
Marker #32 | 9467 | 0.8994 | 0.3867 | 0.0006 | 0.0640 | <0.0001 | 0.0004 | <0.0001 | <0.0001 | <0.0001 | strong |
Marker #36 (KPNA2) | 7943 | 0.1490 | 0.3803 | 0.0483 | 0.0044 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | strong |
Marker #39 (p53) | 10946 | 0.2686 | 0.1962 | 0.0192 | <0.0001 | 0.0055 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | strong |
Marker #38 | 9576 | 0.7878 | 0.3611 | 0.0091 | 0.0063 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 | strong |
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Burdelski, C.; Matuszewska, A.; Kluth, M.; Koop, C.; Grupp, K.; Steurer, S.; Wittmer, C.; Minner, S.; Tsourlakis, M.C.; Sauter, G.; Schlomm, T.; Simon, R. Qualitative and Quantitative Requirements for Assessing Prognostic Markers in Prostate Cancer. Microarrays 2014, 3, 137-158. https://doi.org/10.3390/microarrays3020137
Burdelski C, Matuszewska A, Kluth M, Koop C, Grupp K, Steurer S, Wittmer C, Minner S, Tsourlakis MC, Sauter G, Schlomm T, Simon R. Qualitative and Quantitative Requirements for Assessing Prognostic Markers in Prostate Cancer. Microarrays. 2014; 3(2):137-158. https://doi.org/10.3390/microarrays3020137
Chicago/Turabian StyleBurdelski, Christoph, Aleksandra Matuszewska, Martina Kluth, Christina Koop, Katharina Grupp, Stefan Steurer, Corinna Wittmer, Sarah Minner, Maria Christina Tsourlakis, Guido Sauter, Thorsten Schlomm, and Ronald Simon. 2014. "Qualitative and Quantitative Requirements for Assessing Prognostic Markers in Prostate Cancer" Microarrays 3, no. 2: 137-158. https://doi.org/10.3390/microarrays3020137