This pipeline uses various statistical tests to identify miRs whose log2 expression levels correlated to selected clinical features.
Testing the association between 469 miRs and 14 clinical features across 363 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one miRs.
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1 miR correlated to 'AGE'.
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HSA-MIR-627
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34 miRs correlated to 'PATHOLOGY.T.STAGE'.
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HSA-MIR-3676 , HSA-MIR-133A-1 , HSA-MIR-30A , HSA-MIR-222 , HSA-MIR-221 , ...
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11 miRs correlated to 'PATHOLOGY.N.STAGE'.
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HSA-MIR-133A-2 , HSA-MIR-3676 , HSA-MIR-221 , HSA-MIR-133B , HSA-MIR-217 , ...
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1 miR correlated to 'HISTOLOGICAL.TYPE'.
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HSA-MIR-10A
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1 miR correlated to 'COMPLETENESS.OF.RESECTION'.
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HSA-MIR-3676
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11 miRs correlated to 'NUMBER.OF.LYMPH.NODES'.
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HSA-MIR-133A-2 , HSA-MIR-221 , HSA-MIR-133B , HSA-MIR-3676 , HSA-MIR-217 , ...
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43 miRs correlated to 'GLEASON_SCORE_COMBINED'.
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HSA-MIR-133B , HSA-MIR-133A-2 , HSA-MIR-1-2 , HSA-MIR-217 , HSA-MIR-221 , ...
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43 miRs correlated to 'GLEASON_SCORE_PRIMARY'.
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HSA-MIR-221 , HSA-MIR-133B , HSA-MIR-1-2 , HSA-MIR-133A-2 , HSA-MIR-222 , ...
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6 miRs correlated to 'GLEASON_SCORE_SECONDARY'.
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HSA-MIR-133B , HSA-MIR-592 , HSA-MIR-217 , HSA-MIR-133A-2 , HSA-MIR-514-3 , ...
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43 miRs correlated to 'GLEASON_SCORE'.
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HSA-MIR-133B , HSA-MIR-133A-2 , HSA-MIR-217 , HSA-MIR-1-2 , HSA-MIR-221 , ...
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17 miRs correlated to 'PSA_RESULT_PREOP'.
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HSA-MIR-145 , HSA-MIR-222 , HSA-MIR-221 , HSA-MIR-133A-1 , HSA-MIR-15B , ...
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No miRs correlated to 'Time to Death', 'PSA_VALUE', and 'RACE'.
Complete statistical result table is provided in Supplement Table 1
Clinical feature | Statistical test | Significant miRs | Associated with | Associated with | ||
---|---|---|---|---|---|---|
Time to Death | Cox regression test | N=0 | ||||
AGE | Spearman correlation test | N=1 | older | N=1 | younger | N=0 |
PATHOLOGY T STAGE | Spearman correlation test | N=34 | higher stage | N=2 | lower stage | N=32 |
PATHOLOGY N STAGE | Wilcoxon test | N=11 | class1 | N=11 | class0 | N=0 |
HISTOLOGICAL TYPE | Wilcoxon test | N=1 | prostate adenocarcinoma acinar type | N=1 | prostate adenocarcinoma other subtype | N=0 |
COMPLETENESS OF RESECTION | Kruskal-Wallis test | N=1 | ||||
NUMBER OF LYMPH NODES | Spearman correlation test | N=11 | higher number.of.lymph.nodes | N=2 | lower number.of.lymph.nodes | N=9 |
GLEASON_SCORE_COMBINED | Spearman correlation test | N=43 | higher score | N=20 | lower score | N=23 |
GLEASON_SCORE_PRIMARY | Spearman correlation test | N=43 | higher score | N=16 | lower score | N=27 |
GLEASON_SCORE_SECONDARY | Spearman correlation test | N=6 | higher score | N=3 | lower score | N=3 |
GLEASON_SCORE | Spearman correlation test | N=43 | higher score | N=17 | lower score | N=26 |
PSA_RESULT_PREOP | Spearman correlation test | N=17 | higher psa_result_preop | N=1 | lower psa_result_preop | N=16 |
PSA_VALUE | Spearman correlation test | N=0 | ||||
RACE | Kruskal-Wallis test | N=0 |
Time to Death | Duration (Months) | 0.3-151.4 (median=23.9) |
censored | N = 355 | |
death | N = 6 | |
Significant markers | N = 0 |
AGE | Mean (SD) | 60.84 (7) |
Significant markers | N = 1 | |
pos. correlated | 1 | |
neg. correlated | 0 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSA-MIR-627 | 0.2473 | 5.454e-06 | 0.00256 |
PATHOLOGY.T.STAGE | Mean (SD) | 2.6 (0.51) |
N | ||
2 | 149 | |
3 | 208 | |
4 | 4 | |
Significant markers | N = 34 | |
pos. correlated | 2 | |
neg. correlated | 32 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSA-MIR-3676 | -0.3284 | 2.269e-10 | 1.06e-07 |
HSA-MIR-133A-1 | -0.3026 | 4.425e-09 | 2.07e-06 |
HSA-MIR-30A | -0.2952 | 1.083e-08 | 5.06e-06 |
HSA-MIR-222 | -0.2829 | 4.517e-08 | 2.1e-05 |
HSA-MIR-221 | -0.2646 | 3.372e-07 | 0.000157 |
HSA-MIR-145 | -0.2412 | 3.566e-06 | 0.00165 |
HSA-MIR-574 | -0.2405 | 3.821e-06 | 0.00177 |
HSA-MIR-133B | -0.238 | 5.107e-06 | 0.00236 |
HSA-MIR-378C | -0.2372 | 5.205e-06 | 0.0024 |
HSA-MIR-451 | -0.2369 | 5.356e-06 | 0.00246 |
PATHOLOGY.N.STAGE | Labels | N |
class0 | 263 | |
class1 | 44 | |
Significant markers | N = 11 | |
Higher in class1 | 11 | |
Higher in class0 | 0 |
W(pos if higher in 'class1') | wilcoxontestP | Q | AUC | |
---|---|---|---|---|
HSA-MIR-133A-2 | 3276 | 9.361e-06 | 0.00439 | 0.7092 |
HSA-MIR-3676 | 3417 | 2.46e-05 | 0.0115 | 0.699 |
HSA-MIR-221 | 3500 | 2.745e-05 | 0.0128 | 0.6975 |
HSA-MIR-133B | 3552 | 4.657e-05 | 0.0217 | 0.6919 |
HSA-MIR-217 | 7870 | 0.0001318 | 0.0613 | 0.6801 |
HSA-MIR-133A-1 | 3739 | 0.0001733 | 0.0804 | 0.6769 |
HSA-MIR-378 | 3743 | 0.0001784 | 0.0826 | 0.6765 |
HSA-MIR-1-2 | 3750 | 0.0001878 | 0.0867 | 0.6759 |
HSA-MIR-222 | 3788 | 0.0002471 | 0.114 | 0.6727 |
HSA-MIR-21 | 7762 | 0.0002891 | 0.133 | 0.6708 |
HISTOLOGICAL.TYPE | Labels | N |
PROSTATE ADENOCARCINOMA OTHER SUBTYPE | 14 | |
PROSTATE ADENOCARCINOMA ACINAR TYPE | 349 | |
Significant markers | N = 1 | |
Higher in PROSTATE ADENOCARCINOMA ACINAR TYPE | 1 | |
Higher in PROSTATE ADENOCARCINOMA OTHER SUBTYPE | 0 |
W(pos if higher in 'PROSTATE ADENOCARCINOMA ACINAR TYPE') | wilcoxontestP | Q | AUC | |
---|---|---|---|---|
HSA-MIR-10A | c("1129", "0.0006452") | c("1129", "0.0006452") | 0.299 | 0.7689 |
COMPLETENESS.OF.RESECTION | Labels | N |
R0 | 242 | |
R1 | 91 | |
R2 | 5 | |
RX | 11 | |
Significant markers | N = 1 |
ANOVA_P | Q | |
---|---|---|
HSA-MIR-3676 | 0.0001826 | 0.0857 |
NUMBER.OF.LYMPH.NODES | Mean (SD) | 0.34 (1.3) |
Significant markers | N = 11 | |
pos. correlated | 2 | |
neg. correlated | 9 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSA-MIR-133A-2 | -0.266 | 3.467e-06 | 0.00163 |
HSA-MIR-221 | -0.2483 | 1.226e-05 | 0.00574 |
HSA-MIR-133B | -0.2435 | 1.881e-05 | 0.00878 |
HSA-MIR-3676 | -0.2391 | 3.025e-05 | 0.0141 |
HSA-MIR-217 | 0.2285 | 5.963e-05 | 0.0277 |
HSA-MIR-133A-1 | -0.2202 | 0.000111 | 0.0515 |
HSA-MIR-1-2 | -0.2186 | 0.0001255 | 0.0581 |
HSA-MIR-21 | 0.2163 | 0.0001479 | 0.0683 |
HSA-MIR-222 | -0.2149 | 0.0001632 | 0.0752 |
HSA-MIR-378 | -0.2106 | 0.0002226 | 0.102 |
GLEASON_SCORE_COMBINED | Mean (SD) | 7.45 (0.92) |
Significant markers | N = 43 | |
pos. correlated | 20 | |
neg. correlated | 23 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSA-MIR-133B | -0.4192 | 8.526e-17 | 4e-14 |
HSA-MIR-133A-2 | -0.4039 | 2.298e-15 | 1.08e-12 |
HSA-MIR-1-2 | -0.3747 | 1.532e-13 | 7.15e-11 |
HSA-MIR-217 | 0.3727 | 2.094e-13 | 9.76e-11 |
HSA-MIR-221 | -0.3546 | 3.405e-12 | 1.58e-09 |
HSA-MIR-592 | 0.3691 | 1.665e-11 | 7.72e-09 |
HSA-MIR-133A-1 | -0.3381 | 3.686e-11 | 1.71e-08 |
HSA-MIR-21 | 0.3222 | 3.243e-10 | 1.5e-07 |
HSA-MIR-222 | -0.3217 | 3.473e-10 | 1.6e-07 |
HSA-MIR-3676 | -0.3161 | 1e-09 | 4.6e-07 |
GLEASON_SCORE_PRIMARY | Mean (SD) | 3.6 (0.61) |
Score | N | |
2 | 1 | |
3 | 167 | |
4 | 172 | |
5 | 23 | |
Significant markers | N = 43 | |
pos. correlated | 16 | |
neg. correlated | 27 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSA-MIR-221 | -0.3691 | 3.676e-13 | 1.72e-10 |
HSA-MIR-133B | -0.3694 | 4.096e-13 | 1.92e-10 |
HSA-MIR-1-2 | -0.3548 | 3.287e-12 | 1.54e-09 |
HSA-MIR-133A-2 | -0.3552 | 5.37e-12 | 2.5e-09 |
HSA-MIR-222 | -0.3416 | 2.267e-11 | 1.05e-08 |
HSA-MIR-133A-1 | -0.3261 | 1.93e-10 | 8.95e-08 |
HSA-MIR-3676 | -0.3108 | 1.967e-09 | 9.11e-07 |
HSA-MIR-217 | 0.2992 | 6.085e-09 | 2.81e-06 |
HSA-MIR-184 | -0.3102 | 3.519e-08 | 1.62e-05 |
HSA-MIR-425 | 0.2818 | 4.74e-08 | 2.18e-05 |
GLEASON_SCORE_SECONDARY | Mean (SD) | 3.85 (0.64) |
Score | N | |
3 | 106 | |
4 | 205 | |
5 | 52 | |
Significant markers | N = 6 | |
pos. correlated | 3 | |
neg. correlated | 3 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSA-MIR-133B | -0.2323 | 8.186e-06 | 0.00384 |
HSA-MIR-592 | 0.2462 | 1.089e-05 | 0.0051 |
HSA-MIR-217 | 0.2205 | 2.244e-05 | 0.0105 |
HSA-MIR-133A-2 | -0.2225 | 2.337e-05 | 0.0109 |
HSA-MIR-514-3 | -0.2364 | 0.0004179 | 0.194 |
HSA-MIR-21 | 0.1826 | 0.0004718 | 0.219 |
GLEASON_SCORE | Mean (SD) | 7.51 (0.95) |
Score | N | |
6 | 31 | |
7 | 199 | |
8 | 51 | |
9 | 80 | |
10 | 2 | |
Significant markers | N = 43 | |
pos. correlated | 17 | |
neg. correlated | 26 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSA-MIR-133B | -0.3757 | 1.513e-13 | 7.09e-11 |
HSA-MIR-133A-2 | -0.3622 | 1.924e-12 | 9.01e-10 |
HSA-MIR-217 | 0.3536 | 3.94e-12 | 1.84e-09 |
HSA-MIR-1-2 | -0.352 | 5.014e-12 | 2.34e-09 |
HSA-MIR-221 | -0.3462 | 1.17e-11 | 5.44e-09 |
HSA-MIR-222 | -0.3274 | 1.629e-10 | 7.56e-08 |
HSA-MIR-592 | 0.333 | 1.621e-09 | 7.51e-07 |
HSA-MIR-133A-1 | -0.3049 | 3.006e-09 | 1.39e-06 |
HSA-MIR-3676 | -0.3032 | 5.009e-09 | 2.31e-06 |
HSA-MIR-21 | 0.2888 | 2.096e-08 | 9.64e-06 |
PSA_RESULT_PREOP | Mean (SD) | 10.6 (11) |
Significant markers | N = 17 | |
pos. correlated | 1 | |
neg. correlated | 16 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
HSA-MIR-145 | -0.2449 | 2.484e-06 | 0.00117 |
HSA-MIR-222 | -0.241 | 3.639e-06 | 0.0017 |
HSA-MIR-221 | -0.2348 | 6.54e-06 | 0.00305 |
HSA-MIR-133A-1 | -0.2208 | 2.302e-05 | 0.0107 |
HSA-MIR-15B | 0.2159 | 3.53e-05 | 0.0164 |
HSA-MIR-100 | -0.2124 | 4.748e-05 | 0.022 |
HSA-MIR-204 | -0.2075 | 7.105e-05 | 0.0329 |
HSA-MIR-3647 | -0.2035 | 0.0001012 | 0.0468 |
HSA-MIR-130A | -0.201 | 0.0001201 | 0.0554 |
HSA-MIR-1-2 | -0.198 | 0.0001525 | 0.0702 |
PSA_VALUE | Mean (SD) | 0.98 (3.5) |
Significant markers | N = 0 |
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Expresson data file = PRAD-TP.miRseq_RPKM_log2.txt
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Clinical data file = PRAD-TP.merged_data.txt
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Number of patients = 363
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Number of miRs = 469
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Number of clinical features = 14
For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels
For continuous numerical clinical features, Spearman's rank correlation coefficients (Spearman 1904) and two-tailed P values were estimated using 'cor.test' function in R
For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R
For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R
For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.
In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.