This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features.
Testing the association between 18294 genes and 12 clinical features across 1010 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.
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16 genes correlated to 'Time to Death'.
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PGK1|5230 , MAFA|389692 , NFKBIA|4792 , IRF2|3660 , SUSD3|203328 , ...
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1577 genes correlated to 'AGE'.
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ESR1|2099 , DSC2|1824 , TMEFF1|8577 , DZIP1|22873 , LRFN5|145581 , ...
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148 genes correlated to 'NEOPLASM.DISEASESTAGE'.
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MMRN1|22915 , ABCA9|10350 , LHFP|10186 , ABCA10|10349 , C7|730 , ...
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123 genes correlated to 'PATHOLOGY.T.STAGE'.
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NDNL2|56160 , ZMYM6|9204 , ERMN|57471 , TLR10|81793 , SELE|6401 , ...
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56 genes correlated to 'PATHOLOGY.N.STAGE'.
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NR2F2|7026 , HMSD|284293 , SVEP1|79987 , HTR2B|3357 , F2R|2149 , ...
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1207 genes correlated to 'PATHOLOGY.M.STAGE'.
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NACA2|342538 , HOOK2|29911 , SSBP4|170463 , CCDC130|81576 , RNH1|6050 , ...
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5 genes correlated to 'GENDER'.
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SLC39A11|201266 , FAM104A|84923 , CSNK1D|1453 , GINS2|51659 , TMEM49|81671
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6528 genes correlated to 'HISTOLOGICAL.TYPE'.
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CDH1|999 , RAPGEF3|10411 , TENC1|23371 , AVPR2|554 , PSMD12|5718 , ...
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923 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
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SELO|83642 , PAK2|5062 , ZBTB17|7709 , RING1|6015 , CAPN10|11132 , ...
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40 genes correlated to 'NUMBER.OF.LYMPH.NODES'.
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HMSD|284293 , SNED1|25992 , POU4F1|5457 , PODN|127435 , HTR2B|3357 , ...
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5204 genes correlated to 'RACE'.
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CRYBB2|1415 , FAM3A|60343 , CROCCL1|84809 , LOC90784|90784 , LRRC37A2|474170 , ...
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No genes correlated to 'ETHNICITY'
Complete statistical result table is provided in Supplement Table 1
Table 1. Get Full Table This table shows the clinical features, statistical methods used, and the number of genes that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.
Clinical feature | Statistical test | Significant genes | Associated with | Associated with | ||
---|---|---|---|---|---|---|
Time to Death | Cox regression test | N=16 | shorter survival | N=6 | longer survival | N=10 |
AGE | Spearman correlation test | N=1577 | older | N=426 | younger | N=1151 |
NEOPLASM DISEASESTAGE | Kruskal-Wallis test | N=148 | ||||
PATHOLOGY T STAGE | Spearman correlation test | N=123 | higher stage | N=30 | lower stage | N=93 |
PATHOLOGY N STAGE | Spearman correlation test | N=56 | higher stage | N=46 | lower stage | N=10 |
PATHOLOGY M STAGE | Kruskal-Wallis test | N=1207 | ||||
GENDER | Wilcoxon test | N=5 | male | N=5 | female | N=0 |
HISTOLOGICAL TYPE | Kruskal-Wallis test | N=6528 | ||||
RADIATIONS RADIATION REGIMENINDICATION | Wilcoxon test | N=923 | yes | N=923 | no | N=0 |
NUMBER OF LYMPH NODES | Spearman correlation test | N=40 | higher number.of.lymph.nodes | N=34 | lower number.of.lymph.nodes | N=6 |
RACE | Kruskal-Wallis test | N=5204 | ||||
ETHNICITY | Wilcoxon test | N=0 |
Table S1. Basic characteristics of clinical feature: 'Time to Death'
Time to Death | Duration (Months) | 0-234.3 (median=21.5) |
censored | N = 872 | |
death | N = 117 | |
Significant markers | N = 16 | |
associated with shorter survival | 6 | |
associated with longer survival | 10 |
Table S2. Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test
HazardRatio | Wald_P | Q | C_index | |
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PGK1|5230 | 2 | 1.035e-07 | 0.0019 | 0.682 |
MAFA|389692 | 1.61 | 1.63e-07 | 0.003 | 0.705 |
NFKBIA|4792 | 0.44 | 1.809e-07 | 0.0033 | 0.362 |
IRF2|3660 | 0.34 | 9.568e-07 | 0.018 | 0.357 |
SUSD3|203328 | 0.82 | 1.336e-06 | 0.024 | 0.333 |
PARP3|10039 | 0.6 | 1.699e-06 | 0.031 | 0.357 |
TNFRSF14|8764 | 0.66 | 2.177e-06 | 0.04 | 0.39 |
LRP11|84918 | 1.73 | 2.256e-06 | 0.041 | 0.617 |
DIP2B|57609 | 2.2 | 4.106e-06 | 0.075 | 0.581 |
PCMT1|5110 | 2.1 | 4.845e-06 | 0.089 | 0.661 |
Table S3. Basic characteristics of clinical feature: 'AGE'
AGE | Mean (SD) | 58.65 (13) |
Significant markers | N = 1577 | |
pos. correlated | 426 | |
neg. correlated | 1151 |
Table S4. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
ESR1|2099 | 0.3492 | 5.771e-30 | 1.06e-25 |
DSC2|1824 | -0.261 | 5.453e-17 | 9.97e-13 |
TMEFF1|8577 | -0.257 | 1.665e-16 | 3.05e-12 |
DZIP1|22873 | -0.2553 | 2.668e-16 | 4.88e-12 |
LRFN5|145581 | -0.253 | 1.139e-15 | 2.08e-11 |
ZNF521|25925 | -0.2484 | 1.742e-15 | 3.19e-11 |
RELN|5649 | -0.2473 | 5.742e-15 | 1.05e-10 |
TFPI2|7980 | -0.2432 | 9.093e-15 | 1.66e-10 |
FAT2|2196 | -0.2423 | 9.312e-15 | 1.7e-10 |
TNFSF11|8600 | -0.2428 | 1.34e-14 | 2.45e-10 |
Table S5. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'
NEOPLASM.DISEASESTAGE | Labels | N |
STAGE I | 80 | |
STAGE IA | 80 | |
STAGE IB | 10 | |
STAGE II | 9 | |
STAGE IIA | 341 | |
STAGE IIB | 228 | |
STAGE III | 2 | |
STAGE IIIA | 138 | |
STAGE IIIB | 27 | |
STAGE IIIC | 59 | |
STAGE IV | 17 | |
STAGE TIS | 1 | |
STAGE X | 17 | |
Significant markers | N = 148 |
Table S6. Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'
ANOVA_P | Q | |
---|---|---|
MMRN1|22915 | 1.453e-10 | 2.66e-06 |
ABCA9|10350 | 5.392e-09 | 9.86e-05 |
LHFP|10186 | 6.848e-09 | 0.000125 |
ABCA10|10349 | 7.215e-09 | 0.000132 |
C7|730 | 7.812e-09 | 0.000143 |
MFAP4|4239 | 8.974e-09 | 0.000164 |
GLI1|2735 | 1.023e-08 | 0.000187 |
SDPR|8436 | 1.327e-08 | 0.000243 |
CCL14|6358 | 2.055e-08 | 0.000376 |
SPARCL1|8404 | 2.156e-08 | 0.000394 |
Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'
PATHOLOGY.T.STAGE | Mean (SD) | 1.93 (0.72) |
N | ||
1 | 264 | |
2 | 589 | |
3 | 118 | |
4 | 36 | |
Significant markers | N = 123 | |
pos. correlated | 30 | |
neg. correlated | 93 |
Table S8. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
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NDNL2|56160 | -0.1758 | 1.975e-08 | 0.000361 |
ZMYM6|9204 | -0.1748 | 2.349e-08 | 0.00043 |
ERMN|57471 | -0.173 | 3.43e-08 | 0.000627 |
TLR10|81793 | -0.1701 | 5.904e-08 | 0.00108 |
SELE|6401 | -0.1686 | 7.438e-08 | 0.00136 |
ZNF167|55888 | -0.1658 | 1.235e-07 | 0.00226 |
FAM189A1|23359 | -0.1679 | 1.537e-07 | 0.00281 |
C14ORF139|79686 | -0.1641 | 1.628e-07 | 0.00298 |
MIAT|440823 | -0.1616 | 2.512e-07 | 0.00459 |
SEMA3D|223117 | -0.1614 | 2.729e-07 | 0.00499 |
Table S9. Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'
PATHOLOGY.N.STAGE | Mean (SD) | 0.77 (0.91) |
N | ||
0 | 477 | |
1 | 335 | |
2 | 111 | |
3 | 70 | |
Significant markers | N = 56 | |
pos. correlated | 46 | |
neg. correlated | 10 |
Table S10. Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
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NR2F2|7026 | 0.1838 | 5.375e-09 | 9.83e-05 |
HMSD|284293 | -0.2349 | 1.094e-08 | 2e-04 |
SVEP1|79987 | 0.1736 | 3.731e-08 | 0.000682 |
HTR2B|3357 | 0.1728 | 4.288e-08 | 0.000784 |
F2R|2149 | 0.1706 | 6.329e-08 | 0.00116 |
SNED1|25992 | 0.1677 | 1.057e-07 | 0.00193 |
LTBP2|4053 | 0.1608 | 3.478e-07 | 0.00636 |
NUDT4|11163 | 0.1606 | 3.613e-07 | 0.00661 |
PODN|127435 | 0.1602 | 3.897e-07 | 0.00713 |
CHI3L2|1117 | -0.1569 | 6.816e-07 | 0.0125 |
Table S11. Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'
PATHOLOGY.M.STAGE | Labels | N |
CM0 (I+) | 2 | |
M0 | 859 | |
M1 | 17 | |
MX | 132 | |
Significant markers | N = 1207 |
Table S12. Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'
ANOVA_P | Q | |
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NACA2|342538 | 1.077e-13 | 1.97e-09 |
HOOK2|29911 | 1.36e-13 | 2.49e-09 |
SSBP4|170463 | 9.737e-13 | 1.78e-08 |
CCDC130|81576 | 1.188e-12 | 2.17e-08 |
RNH1|6050 | 1.898e-12 | 3.47e-08 |
VENTX|27287 | 2.366e-12 | 4.33e-08 |
NEURL2|140825 | 4.654e-12 | 8.51e-08 |
AKAP8|10270 | 5.355e-12 | 9.79e-08 |
TSSK6|83983 | 5.423e-12 | 9.92e-08 |
SLC39A13|91252 | 7.573e-12 | 1.38e-07 |
Table S13. Basic characteristics of clinical feature: 'GENDER'
GENDER | Labels | N |
FEMALE | 999 | |
MALE | 11 | |
Significant markers | N = 5 | |
Higher in MALE | 5 | |
Higher in FEMALE | 0 |
Table S14. Get Full Table List of 5 genes differentially expressed by 'GENDER'. 6 significant gene(s) located in sex chromosomes is(are) filtered out.
W(pos if higher in 'MALE') | wilcoxontestP | Q | AUC | |
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SLC39A11|201266 | 9961 | 3.46e-06 | 0.0624 | 0.9065 |
FAM104A|84923 | 9895 | 4.811e-06 | 0.0868 | 0.9004 |
CSNK1D|1453 | 9813 | 7.201e-06 | 0.13 | 0.893 |
GINS2|51659 | 9690 | 1.302e-05 | 0.235 | 0.8818 |
TMEM49|81671 | 9642 | 1.633e-05 | 0.295 | 0.8774 |
Table S15. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'
HISTOLOGICAL.TYPE | Labels | N |
INFILTRATING CARCINOMA NOS | 1 | |
INFILTRATING DUCTAL CARCINOMA | 749 | |
INFILTRATING LOBULAR CARCINOMA | 167 | |
MEDULLARY CARCINOMA | 5 | |
MIXED HISTOLOGY (PLEASE SPECIFY) | 29 | |
MUCINOUS CARCINOMA | 14 | |
OTHER SPECIFY | 44 | |
Significant markers | N = 6528 |
Table S16. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'
ANOVA_P | Q | |
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CDH1|999 | 1.008e-56 | 1.84e-52 |
RAPGEF3|10411 | 2.775e-41 | 5.08e-37 |
TENC1|23371 | 3.492e-38 | 6.39e-34 |
AVPR2|554 | 1.452e-37 | 2.66e-33 |
PSMD12|5718 | 7.646e-37 | 1.4e-32 |
PSMD14|10213 | 8.616e-37 | 1.58e-32 |
ADAM33|80332 | 2.813e-36 | 5.14e-32 |
LRRC70|100130733 | 5.274e-36 | 9.64e-32 |
MUSTN1|389125 | 6.204e-36 | 1.13e-31 |
USHBP1|83878 | 7.863e-36 | 1.44e-31 |
923 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
Table S17. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 285 | |
YES | 725 | |
Significant markers | N = 923 | |
Higher in YES | 923 | |
Higher in NO | 0 |
Table S18. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'
W(pos if higher in 'YES') | wilcoxontestP | Q | AUC | |
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SELO|83642 | 132103 | 5.191e-12 | 9.5e-08 | 0.6393 |
PAK2|5062 | 76184 | 7.93e-11 | 1.45e-06 | 0.6313 |
ZBTB17|7709 | 130110 | 1.34e-10 | 2.45e-06 | 0.6297 |
RING1|6015 | 129823 | 2.101e-10 | 3.84e-06 | 0.6283 |
CAPN10|11132 | 129754 | 2.339e-10 | 4.28e-06 | 0.628 |
BBC3|27113 | 129696 | 2.559e-10 | 4.68e-06 | 0.6277 |
FAM100A|124402 | 129306 | 4.668e-10 | 8.54e-06 | 0.6258 |
ZNF513|130557 | 129209 | 5.413e-10 | 9.9e-06 | 0.6253 |
IDUA|3425 | 129078 | 6.606e-10 | 1.21e-05 | 0.6247 |
NBN|4683 | 77673 | 7.994e-10 | 1.46e-05 | 0.6241 |
Table S19. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'
NUMBER.OF.LYMPH.NODES | Mean (SD) | 2.33 (4.6) |
Significant markers | N = 40 | |
pos. correlated | 34 | |
neg. correlated | 6 |
Table S20. Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
HMSD|284293 | -0.2559 | 5.4e-09 | 9.88e-05 |
SNED1|25992 | 0.1906 | 2.134e-08 | 0.00039 |
POU4F1|5457 | -0.2454 | 5.294e-08 | 0.000968 |
PODN|127435 | 0.1792 | 1.436e-07 | 0.00263 |
HTR2B|3357 | 0.1725 | 4.229e-07 | 0.00774 |
NR2F2|7026 | 0.1709 | 5.403e-07 | 0.00988 |
F2R|2149 | 0.1692 | 6.942e-07 | 0.0127 |
NUDT4|11163 | 0.1641 | 1.504e-06 | 0.0275 |
SVEP1|79987 | 0.1613 | 2.319e-06 | 0.0424 |
LRRC32|2615 | 0.1603 | 2.631e-06 | 0.0481 |
Table S21. Basic characteristics of clinical feature: 'RACE'
RACE | Labels | N |
AMERICAN INDIAN OR ALASKA NATIVE | 1 | |
ASIAN | 57 | |
BLACK OR AFRICAN AMERICAN | 139 | |
WHITE | 718 | |
Significant markers | N = 5204 |
Table S22. Get Full Table List of top 10 genes differentially expressed by 'RACE'
ANOVA_P | Q | |
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CRYBB2|1415 | 1.372e-31 | 2.51e-27 |
FAM3A|60343 | 1.865e-26 | 3.41e-22 |
CROCCL1|84809 | 4.652e-26 | 8.51e-22 |
LOC90784|90784 | 1.245e-25 | 2.28e-21 |
LRRC37A2|474170 | 1.793e-25 | 3.28e-21 |
C14ORF167|55449 | 2.815e-24 | 5.15e-20 |
TOP1MT|116447 | 3.621e-23 | 6.62e-19 |
TRMT2A|27037 | 4.523e-23 | 8.27e-19 |
MPST|4357 | 7.264e-23 | 1.33e-18 |
TSPO|706 | 7.952e-23 | 1.45e-18 |
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Expresson data file = BRCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
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Clinical data file = BRCA-TP.merged_data.txt
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Number of patients = 1010
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Number of genes = 18294
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Number of clinical features = 12
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 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 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 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.