Correlation between mRNAseq expression and clinical features
Breast Invasive Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1X63KRJ
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/C1X63KRJ
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 18296 genes and 12 clinical features across 1039 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 23 genes correlated to 'Time to Death'.

    • NFKBIA|4792 ,  PGK1|5230 ,  TNFRSF14|8764 ,  LRP11|84918 ,  SUSD3|203328 ,  ...

  • 1650 genes correlated to 'AGE'.

    • ESR1|2099 ,  DSC2|1824 ,  TMEFF1|8577 ,  ZNF521|25925 ,  LRFN5|145581 ,  ...

  • 48 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • MMRN1|22915 ,  ABCA9|10350 ,  GLI1|2735 ,  MFAP4|4239 ,  C18ORF34|374864 ,  ...

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

    • ZMYM6|9204 ,  ERMN|57471 ,  NDNL2|56160 ,  IKZF4|64375 ,  SELE|6401 ,  ...

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

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

  • 2236 genes correlated to 'PATHOLOGY.M.STAGE'.

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

  • 5 genes correlated to 'GENDER'.

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

  • 6817 genes correlated to 'HISTOLOGICAL.TYPE'.

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

  • 1408 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

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

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

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

  • 5797 genes correlated to 'RACE'.

    • CRYBB2|1415 ,  CROCCL1|84809 ,  FAM3A|60343 ,  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=23 shorter survival N=8 longer survival N=15
AGE Spearman correlation test N=1650 older N=442 younger N=1208
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=48        
PATHOLOGY T STAGE Spearman correlation test N=127 higher stage N=31 lower stage N=96
PATHOLOGY N STAGE Spearman correlation test N=53 higher stage N=43 lower stage N=10
PATHOLOGY M STAGE Kruskal-Wallis test N=2236        
GENDER Wilcoxon test N=5 male N=5 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test N=6817        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=1408 yes N=1408 no N=0
NUMBER OF LYMPH NODES Spearman correlation test N=38 higher number.of.lymph.nodes N=30 lower number.of.lymph.nodes N=8
RACE Kruskal-Wallis test N=5797        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'Time to Death'

23 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=22.8)
  censored N = 897
  death N = 122
     
  Significant markers N = 23
  associated with shorter survival 8
  associated with longer survival 15
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
NFKBIA|4792 0.44 6.509e-08 0.0012 0.354
PGK1|5230 1.95 3.04e-07 0.0056 0.677
TNFRSF14|8764 0.64 4.653e-07 0.0085 0.385
LRP11|84918 1.77 5.13e-07 0.0094 0.618
SUSD3|203328 0.82 7.162e-07 0.013 0.334
MAFA|389692 1.54 1.567e-06 0.029 0.685
PARP3|10039 0.61 1.82e-06 0.033 0.361
PCMT1|5110 2.1 3.244e-06 0.059 0.653
MAP2K6|5608 0.71 4.188e-06 0.077 0.38
UBA7|7318 0.67 4.197e-06 0.077 0.366
Clinical variable #2: 'AGE'

1650 genes related to 'AGE'.

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

AGE Mean (SD) 58.62 (13)
  Significant markers N = 1650
  pos. correlated 442
  neg. correlated 1208
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 0.3463 2.798e-30 5.12e-26
DSC2|1824 -0.2603 2.384e-17 4.36e-13
TMEFF1|8577 -0.2538 1.5e-16 2.74e-12
ZNF521|25925 -0.2533 1.724e-16 3.15e-12
LRFN5|145581 -0.2564 1.805e-16 3.3e-12
DZIP1|22873 -0.25 4.358e-16 7.97e-12
RELN|5649 -0.2533 4.854e-16 8.88e-12
FAT2|2196 -0.2438 2.606e-15 4.77e-11
PCDH18|54510 -0.2412 4.739e-15 8.67e-11
TFPI2|7980 -0.2422 4.804e-15 8.79e-11
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

48 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S5.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 83
  STAGE IA 83
  STAGE IB 10
  STAGE II 5
  STAGE IIA 347
  STAGE IIB 238
  STAGE III 2
  STAGE IIIA 142
  STAGE IIIB 29
  STAGE IIIC 63
  STAGE IV 18
  STAGE TIS 1
  STAGE X 17
     
  Significant markers N = 48
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 9.303e-08 0.0017
ABCA9|10350 1.008e-07 0.00184
GLI1|2735 2.339e-07 0.00428
MFAP4|4239 3.132e-07 0.00573
C18ORF34|374864 4.526e-07 0.00828
SVEP1|79987 6.194e-07 0.0113
F2RL2|2151 6.808e-07 0.0125
CCL14|6358 7.794e-07 0.0143
PODN|127435 8.109e-07 0.0148
LHFP|10186 8.921e-07 0.0163
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 1.93 (0.73)
  N
  1 271
  2 601
  3 125
  4 39
     
  Significant markers N = 127
  pos. correlated 31
  neg. correlated 96
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
ZMYM6|9204 -0.1788 6.845e-09 0.000125
ERMN|57471 -0.1732 2.126e-08 0.000389
NDNL2|56160 -0.1653 8.756e-08 0.0016
IKZF4|64375 -0.1624 1.472e-07 0.00269
SELE|6401 -0.1617 1.698e-07 0.00311
ADAMTS6|11174 -0.1612 1.835e-07 0.00336
TLR10|81793 -0.1613 1.9e-07 0.00348
SEMA3D|223117 -0.16 2.375e-07 0.00434
SERPINB8|5271 -0.1592 2.614e-07 0.00478
ARAF|369 0.1589 2.716e-07 0.00497
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.78 (0.91)
  N
  0 489
  1 344
  2 113
  3 74
     
  Significant markers N = 53
  pos. correlated 43
  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
HMSD|284293 -0.2305 1.22e-08 0.000223
SVEP1|79987 0.174 2.248e-08 0.000411
NR2F2|7026 0.1725 2.979e-08 0.000545
HTR2B|3357 0.1691 5.531e-08 0.00101
F2R|2149 0.1672 7.872e-08 0.00144
SNED1|25992 0.1647 1.231e-07 0.00225
PODN|127435 0.1604 2.628e-07 0.00481
THBS4|7060 0.1552 6.456e-07 0.0118
CHI3L2|1117 -0.1543 7.439e-07 0.0136
NUDT4|11163 0.1533 8.668e-07 0.0159
Clinical variable #6: 'PATHOLOGY.M.STAGE'

2236 genes related to 'PATHOLOGY.M.STAGE'.

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  CM0 (I+) 5
  M0 868
  M1 19
  MX 147
     
  Significant markers N = 2236
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 9.014e-18 1.65e-13
HOOK2|29911 2.513e-16 4.6e-12
RNH1|6050 2.636e-16 4.82e-12
CCDC130|81576 3.674e-16 6.72e-12
SSBP4|170463 1.254e-15 2.29e-11
DDX6|1656 1.331e-15 2.43e-11
SLC39A13|91252 3.024e-15 5.53e-11
NEURL2|140825 5.052e-15 9.24e-11
LZTR1|8216 5.941e-15 1.09e-10
TSSK6|83983 7.076e-15 1.29e-10
Clinical variable #7: 'GENDER'

5 genes related to 'GENDER'.

Table S13.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 1028
  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 10258 3.317e-06 0.0599 0.9071
FAM104A|84923 10198 4.442e-06 0.0802 0.9018
CSNK1D|1453 10087 7.554e-06 0.136 0.892
GINS2|51659 9971 1.299e-05 0.234 0.8818
TMEM49|81671 9939 1.505e-05 0.272 0.8789
Clinical variable #8: 'HISTOLOGICAL.TYPE'

6817 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 768
  INFILTRATING LOBULAR CARCINOMA 175
  MEDULLARY CARCINOMA 6
  MIXED HISTOLOGY (PLEASE SPECIFY) 29
  MUCINOUS CARCINOMA 15
  OTHER SPECIFY 44
     
  Significant markers N = 6817
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 7.425e-60 1.36e-55
RAPGEF3|10411 2.748e-41 5.03e-37
TENC1|23371 8.565e-40 1.57e-35
AVPR2|554 5.674e-39 1.04e-34
PSMD12|5718 2.697e-38 4.93e-34
ADAM33|80332 2.696e-37 4.93e-33
GMPS|8833 6.282e-37 1.15e-32
USHBP1|83878 1.303e-36 2.38e-32
CSE1L|1434 2.306e-36 4.22e-32
PSMD14|10213 3.269e-36 5.98e-32
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

1408 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S17.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 285
  YES 754
     
  Significant markers N = 1408
  Higher in YES 1408
  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 139845 6.02e-14 1.1e-09 0.6508
ZBTB17|7709 137565 2.966e-12 5.43e-08 0.6402
CAPN10|11132 137561 2.986e-12 5.46e-08 0.6401
RING1|6015 137451 3.578e-12 6.55e-08 0.6396
PAK2|5062 77680 5.309e-12 9.71e-08 0.6385
BBC3|27113 136966 7.89e-12 1.44e-07 0.6374
ZNF513|130557 136643 1.327e-11 2.43e-07 0.6359
CROCC|9696 136640 1.333e-11 2.44e-07 0.6359
FAM100A|124402 136322 2.212e-11 4.05e-07 0.6344
IDUA|3425 136142 2.939e-11 5.37e-07 0.6335
Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

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

Table S19.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.38 (4.7)
  Significant markers N = 38
  pos. correlated 30
  neg. correlated 8
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 -0.2491 8.203e-09 0.00015
SNED1|25992 0.1851 3.43e-08 0.000628
PODN|127435 0.1812 6.688e-08 0.00122
POU4F1|5457 -0.2315 1.857e-07 0.0034
HTR2B|3357 0.1681 5.634e-07 0.0103
NR2F2|7026 0.1642 1.026e-06 0.0188
F2R|2149 0.1607 1.735e-06 0.0317
SVEP1|79987 0.1607 1.764e-06 0.0323
CERCAM|51148 0.1602 1.891e-06 0.0346
CBFA2T3|863 0.1593 2.15e-06 0.0393
Clinical variable #11: 'RACE'

5797 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 160
  WHITE 726
     
  Significant markers N = 5797
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 9.321e-34 1.71e-29
CROCCL1|84809 2.653e-32 4.85e-28
FAM3A|60343 9.887e-30 1.81e-25
LOC90784|90784 8.435e-29 1.54e-24
LRRC37A2|474170 2.229e-28 4.08e-24
C14ORF167|55449 2.84e-28 5.19e-24
TRMT2A|27037 4.712e-27 8.62e-23
TRABD|80305 2.099e-26 3.84e-22
TOP1MT|116447 3.303e-26 6.04e-22
TSPO|706 7.516e-26 1.37e-21
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 832
     
  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 = 1039

  • Number of genes = 18296

  • 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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