Correlation between mRNAseq expression and clinical features
Breast Invasive Carcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1BZ64N8
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/C1BZ64N8
Overview
Introduction

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

Summary

Testing the association between 18295 genes and 10 clinical features across 984 samples, statistically thresholded by Q value < 0.05, 9 clinical features related to at least one genes.

  • 1095 genes correlated to 'AGE'.

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

  • 98 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • MMRN1|22915 ,  SDPR|8436 ,  LHFP|10186 ,  ABCA10|10349 ,  SPARCL1|8404 ,  ...

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

    • ZMYM6|9204 ,  ERMN|57471 ,  NDNL2|56160 ,  TLR10|81793 ,  ZNF167|55888 ,  ...

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

    • HMSD|284293 ,  NR2F2|7026 ,  HTR2B|3357 ,  SVEP1|79987 ,  SNED1|25992 ,  ...

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

    • CCDC130|81576 ,  NACA2|342538 ,  PPIAL4G|644591 ,  HOOK2|29911 ,  EXD3|54932 ,  ...

  • 19 genes correlated to 'GENDER'.

    • NLGN4Y|22829 ,  ZFY|7544 ,  PRKY|5616 ,  SYT9|143425 ,  GSTA1|2938 ,  ...

  • 5620 genes correlated to 'HISTOLOGICAL.TYPE'.

    • CDH1|999 ,  RAPGEF3|10411 ,  USHBP1|83878 ,  AVPR2|554 ,  PSMD14|10213 ,  ...

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

    • SELO|83642 ,  NACA2|342538 ,  FAM100A|124402 ,  KIF20B|9585 ,  C19ORF6|91304 ,  ...

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

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

  • No genes correlated to 'Time to Death'

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 Q value < 0.05.

Clinical feature Statistical test Significant genes Associated with                 Associated with
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=1095 older N=288 younger N=807
NEOPLASM DISEASESTAGE ANOVA test N=98        
PATHOLOGY T STAGE Spearman correlation test N=35 higher stage N=5 lower stage N=30
PATHOLOGY N STAGE Spearman correlation test N=16 higher stage N=13 lower stage N=3
PATHOLOGY M STAGE ANOVA test N=388        
GENDER t test N=19 male N=8 female N=11
HISTOLOGICAL TYPE ANOVA test N=5620        
RADIATIONS RADIATION REGIMENINDICATION t test N=344 yes N=150 no N=194
NUMBER OF LYMPH NODES Spearman correlation test N=7 higher number.of.lymph.nodes N=5 lower number.of.lymph.nodes N=2
Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0-234.3 (median=21.6)
  censored N = 848
  death N = 115
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

1095 genes related to 'AGE'.

Table S2.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 58.61 (13)
  Significant markers N = 1095
  pos. correlated 288
  neg. correlated 807
List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
ESR1|2099 0.3584 8.456e-31 1.55e-26
DSC2|1824 -0.2684 1.745e-17 3.19e-13
TMEFF1|8577 -0.2586 2.686e-16 4.91e-12
DZIP1|22873 -0.2579 3.204e-16 5.86e-12
LRFN5|145581 -0.2544 1.768e-15 3.23e-11
ZNF521|25925 -0.2496 2.934e-15 5.37e-11
IGSF10|285313 -0.2453 9.81e-15 1.79e-10
TFPI2|7980 -0.2459 1.032e-14 1.89e-10
FAT2|2196 -0.2429 1.752e-14 3.2e-10
TNFSF11|8600 -0.2437 2.359e-14 4.31e-10

Figure S1.  Get High-res Image As an example, this figure shows the association of ESR1|2099 to 'AGE'. P value = 8.46e-31 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

98 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 78
  STAGE IA 77
  STAGE IB 10
  STAGE II 9
  STAGE IIA 332
  STAGE IIB 224
  STAGE III 2
  STAGE IIIA 135
  STAGE IIIB 27
  STAGE IIIC 56
  STAGE IV 15
  STAGE TIS 1
  STAGE X 17
     
  Significant markers N = 98
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
MMRN1|22915 3.164e-10 5.79e-06
SDPR|8436 4.437e-10 8.12e-06
LHFP|10186 7.404e-10 1.35e-05
ABCA10|10349 7.998e-10 1.46e-05
SPARCL1|8404 2.431e-09 4.45e-05
GRRP1|79927 2.959e-09 5.41e-05
ABCA9|10350 2.966e-09 5.42e-05
USHBP1|83878 1.005e-08 0.000184
ADCY4|196883 1.29e-08 0.000236
C7|730 1.339e-08 0.000245

Figure S2.  Get High-res Image As an example, this figure shows the association of MMRN1|22915 to 'NEOPLASM.DISEASESTAGE'. P value = 3.16e-10 with ANOVA analysis.

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

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 1.93 (0.72)
  N
  1 256
  2 573
  3 116
  4 36
     
  Significant markers N = 35
  pos. correlated 5
  neg. correlated 30
List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
ZMYM6|9204 -0.1787 1.758e-08 0.000322
ERMN|57471 -0.1715 6.759e-08 0.00124
NDNL2|56160 -0.1702 8.122e-08 0.00149
TLR10|81793 -0.1695 9.57e-08 0.00175
ZNF167|55888 -0.1629 2.923e-07 0.00535
C14ORF139|79686 -0.1623 3.218e-07 0.00589
SELE|6401 -0.1611 3.955e-07 0.00723
CNN3|1266 -0.1597 4.978e-07 0.0091
PTGER3|5733 -0.1596 5.054e-07 0.00924
CCND2|894 -0.1591 5.463e-07 0.00999

Figure S3.  Get High-res Image As an example, this figure shows the association of ZMYM6|9204 to 'PATHOLOGY.T.STAGE'. P value = 1.76e-08 with Spearman correlation analysis.

Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.77 (0.9)
  N
  0 464
  1 329
  2 108
  3 67
     
  Significant markers N = 16
  pos. correlated 13
  neg. correlated 3
List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HMSD|284293 -0.2404 7.673e-09 0.00014
NR2F2|7026 0.1774 2.757e-08 0.000504
HTR2B|3357 0.1715 7.978e-08 0.00146
SVEP1|79987 0.1695 1.147e-07 0.0021
SNED1|25992 0.1689 1.242e-07 0.00227
F2R|2149 0.1679 1.479e-07 0.0027
NUDT4|11163 0.1622 3.916e-07 0.00716
DAAM1|23002 0.1604 5.231e-07 0.00957
LTBP2|4053 0.1588 6.813e-07 0.0125
RGS4|5999 0.1566 9.826e-07 0.018

Figure S4.  Get High-res Image As an example, this figure shows the association of HMSD|284293 to 'PATHOLOGY.N.STAGE'. P value = 7.67e-09 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  CM0 (I+) 2
  M0 848
  M1 15
  MX 119
     
  Significant markers N = 388
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
CCDC130|81576 1.503e-14 2.75e-10
NACA2|342538 1.913e-13 3.5e-09
PPIAL4G|644591 5.947e-13 1.09e-08
HOOK2|29911 6.997e-13 1.28e-08
EXD3|54932 3.576e-12 6.54e-08
VENTX|27287 6.144e-12 1.12e-07
CNOT4|4850 8.316e-12 1.52e-07
NEURL2|140825 1.748e-11 3.2e-07
SSBP4|170463 3.668e-11 6.71e-07
ID2B|84099 4.324e-11 7.91e-07

Figure S5.  Get High-res Image As an example, this figure shows the association of CCDC130|81576 to 'PATHOLOGY.M.STAGE'. P value = 1.5e-14 with ANOVA analysis.

Clinical variable #7: 'GENDER'

19 genes related to 'GENDER'.

Table S12.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 974
  MALE 10
     
  Significant markers N = 19
  Higher in MALE 8
  Higher in FEMALE 11
List of top 10 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
NLGN4Y|22829 40.79 4.361e-13 7.86e-09 1
ZFY|7544 36.06 1.369e-11 2.47e-07 1
PRKY|5616 30.22 3.565e-11 6.42e-07 1
SYT9|143425 13.83 3.057e-10 5.51e-06 0.7988
GSTA1|2938 -16.89 2.171e-08 0.000391 0.8947
RND2|8153 10.98 1.367e-07 0.00246 0.8319
SUMF2|25870 -8.69 1.663e-07 0.00299 0.7331
RIMS4|140730 11.57 1.739e-07 0.00313 0.8766
MYH16|84176 -12.4 1.799e-07 0.00324 0.8508
HTR4|3360 -12.76 2.437e-07 0.00439 0.8078

Figure S6.  Get High-res Image As an example, this figure shows the association of NLGN4Y|22829 to 'GENDER'. P value = 4.36e-13 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

5620 genes related to 'HISTOLOGICAL.TYPE'.

Table S14.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  INFILTRATING CARCINOMA NOS 1
  INFILTRATING DUCTAL CARCINOMA 733
  INFILTRATING LOBULAR CARCINOMA 158
  MEDULLARY CARCINOMA 5
  MIXED HISTOLOGY (PLEASE SPECIFY) 29
  MUCINOUS CARCINOMA 14
  OTHER SPECIFY 43
     
  Significant markers N = 5620
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
CDH1|999 4.572e-94 8.36e-90
RAPGEF3|10411 4.196e-45 7.68e-41
USHBP1|83878 1.07e-42 1.96e-38
AVPR2|554 5.171e-40 9.46e-36
PSMD14|10213 1.246e-38 2.28e-34
MUSTN1|389125 2.343e-38 4.29e-34
BTG2|7832 1.906e-37 3.49e-33
GPIHBP1|338328 2.492e-37 4.56e-33
KANK3|256949 2.641e-37 4.83e-33
LRRC70|100130733 3.446e-37 6.3e-33

Figure S7.  Get High-res Image As an example, this figure shows the association of CDH1|999 to 'HISTOLOGICAL.TYPE'. P value = 4.57e-94 with ANOVA analysis.

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

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

Table S16.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 285
  YES 699
     
  Significant markers N = 344
  Higher in YES 150
  Higher in NO 194
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
SELO|83642 6.95 9.278e-12 1.7e-07 0.6287
NACA2|342538 6.74 3.267e-11 5.98e-07 0.6063
FAM100A|124402 6.48 1.998e-10 3.65e-06 0.6162
KIF20B|9585 -6.47 2.041e-10 3.73e-06 0.6161
C19ORF6|91304 6.37 3.541e-10 6.48e-06 0.605
C1ORF86|199990 6.35 4.227e-10 7.73e-06 0.6102
RING1|6015 6.3 5.963e-10 1.09e-05 0.6154
SLC39A5|283375 6.26 9.414e-10 1.72e-05 0.6304
ZNF513|130557 6.17 1.252e-09 2.29e-05 0.6148
BAZ1B|9031 -6.1 1.921e-09 3.51e-05 0.6104

Figure S8.  Get High-res Image As an example, this figure shows the association of SELO|83642 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 9.28e-12 with T-test analysis.

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

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

Table S18.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.31 (4.5)
  Significant markers N = 7
  pos. correlated 5
  neg. correlated 2
List of 7 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S19.  Get Full Table List of 7 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
HMSD|284293 -0.2635 3.184e-09 5.83e-05
SNED1|25992 0.1895 4.148e-08 0.000759
POU4F1|5457 -0.2382 2.142e-07 0.00392
PODN|127435 0.1689 1.062e-06 0.0194
HTR2B|3357 0.1688 1.087e-06 0.0199
NUDT4|11163 0.1675 1.307e-06 0.0239
NR2F2|7026 0.1664 1.537e-06 0.0281

Figure S9.  Get High-res Image As an example, this figure shows the association of HMSD|284293 to 'NUMBER.OF.LYMPH.NODES'. P value = 3.18e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

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 = 984

  • Number of genes = 18295

  • Number of clinical features = 10

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)
Copyright © 2014 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle