Correlation between mRNAseq expression and clinical features
Breast Invasive Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1Q23XZ4
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1Q23XZ4
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features.

Summary

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.

  • 16 genes correlated to 'Time to Death'.

    • PGK1|5230 ,  MAFA|389692 ,  NFKBIA|4792 ,  IRF2|3660 ,  SUSD3|203328 ,  ...

  • 1577 genes correlated to 'AGE'.

    • ESR1|2099 ,  DSC2|1824 ,  TMEFF1|8577 ,  DZIP1|22873 ,  LRFN5|145581 ,  ...

  • 148 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • MMRN1|22915 ,  ABCA9|10350 ,  LHFP|10186 ,  ABCA10|10349 ,  C7|730 ,  ...

  • 123 genes correlated to 'PATHOLOGY.T.STAGE'.

    • NDNL2|56160 ,  ZMYM6|9204 ,  ERMN|57471 ,  TLR10|81793 ,  SELE|6401 ,  ...

  • 56 genes correlated to 'PATHOLOGY.N.STAGE'.

    • NR2F2|7026 ,  HMSD|284293 ,  SVEP1|79987 ,  HTR2B|3357 ,  F2R|2149 ,  ...

  • 1207 genes correlated to 'PATHOLOGY.M.STAGE'.

    • NACA2|342538 ,  HOOK2|29911 ,  SSBP4|170463 ,  CCDC130|81576 ,  RNH1|6050 ,  ...

  • 5 genes correlated to 'GENDER'.

    • SLC39A11|201266 ,  FAM104A|84923 ,  CSNK1D|1453 ,  GINS2|51659 ,  TMEM49|81671

  • 6528 genes correlated to 'HISTOLOGICAL.TYPE'.

    • CDH1|999 ,  RAPGEF3|10411 ,  TENC1|23371 ,  AVPR2|554 ,  PSMD12|5718 ,  ...

  • 923 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • SELO|83642 ,  PAK2|5062 ,  ZBTB17|7709 ,  RING1|6015 ,  CAPN10|11132 ,  ...

  • 40 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • HMSD|284293 ,  SNED1|25992 ,  POU4F1|5457 ,  PODN|127435 ,  HTR2B|3357 ,  ...

  • 5204 genes correlated to 'RACE'.

    • CRYBB2|1415 ,  FAM3A|60343 ,  CROCCL1|84809 ,  LOC90784|90784 ,  LRRC37A2|474170 ,  ...

  • No genes correlated to 'ETHNICITY'

Results
Overview of the results

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        
Clinical variable #1: 'Time to Death'

16 genes related to 'Time to Death'.

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
List of top 10 genes differentially expressed by 'Time to Death'

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
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
Clinical variable #2: 'AGE'

1577 genes related to 'AGE'.

Table S3.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 58.65 (13)
  Significant markers N = 1577
  pos. correlated 426
  neg. correlated 1151
List of top 10 genes differentially expressed by 'AGE'

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
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

148 genes related to 'NEOPLASM.DISEASESTAGE'.

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
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

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
Clinical variable #4: 'PATHOLOGY.T.STAGE'

123 genes related to 'PATHOLOGY.T.STAGE'.

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
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
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
Clinical variable #5: 'PATHOLOGY.N.STAGE'

56 genes related to 'PATHOLOGY.N.STAGE'.

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
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
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
Clinical variable #6: 'PATHOLOGY.M.STAGE'

1207 genes related to 'PATHOLOGY.M.STAGE'.

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
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
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
Clinical variable #7: 'GENDER'

5 genes related to 'GENDER'.

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
List of 5 genes differentially expressed by 'GENDER'

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
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
Clinical variable #8: 'HISTOLOGICAL.TYPE'

6528 genes related to 'HISTOLOGICAL.TYPE'.

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
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
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
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

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
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
Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

40 genes related to 'NUMBER.OF.LYMPH.NODES'.

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
List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

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
Clinical variable #11: 'RACE'

5204 genes related to 'RACE'.

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
List of top 10 genes differentially expressed by 'RACE'

Table S22.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
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
Clinical variable #12: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S23.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 36
  NOT HISPANIC OR LATINO 803
     
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = BRCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

  • Clinical data file = BRCA-TP.merged_data.txt

  • Number of patients = 1010

  • Number of genes = 18294

  • Number of clinical features = 12

Survival analysis

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

Correlation analysis

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

ANOVA analysis

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

Student's t-test analysis

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

Q value calculation

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.

Download Results

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.

References
[1] Andersen and Gill, Cox's regression model for counting processes, a large sample study, Annals of Statistics 10(4):1100-1120 (1982)
[2] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[3] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[5] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)
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