Correlation between mRNAseq expression and clinical features
Prostate Adenocarcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1WD3Z74
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/C1WD3Z74
Overview
Introduction

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

Summary

Testing the association between 18258 genes and 13 clinical features across 206 samples, statistically thresholded by Q value < 0.05, 11 clinical features related to at least one genes.

  • 1 gene correlated to 'AGE'.

    • ADAP2|55803

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

    • MT1H|4496 ,  GMDS|2762 ,  FAM189A2|9413 ,  OSGIN2|734 ,  CHRNA2|1135 ,  ...

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

    • NKX6-2|84504 ,  PRTN3|5657 ,  CRHR2|1395 ,  SLMO2|51012 ,  LCNL1|401562 ,  ...

  • 1 gene correlated to 'COMPLETENESS.OF.RESECTION'.

    • GLP2R|9340

  • 60 genes correlated to 'GLEASON_SCORE_COMBINED'.

    • ZNF250|58500 ,  FAM72B|653820 ,  FA2H|79152 ,  SH3RF2|153769 ,  C12ORF48|55010 ,  ...

  • 67 genes correlated to 'GLEASON_SCORE_PRIMARY'.

    • KANK4|163782 ,  METTL6|131965 ,  SH3RF2|153769 ,  C2|717 ,  CD38|952 ,  ...

  • 105 genes correlated to 'GLEASON_SCORE'.

    • FA2H|79152 ,  FAM72A|729533 ,  C12ORF48|55010 ,  FMOD|2331 ,  CCNE2|9134 ,  ...

  • 30 genes correlated to 'PSA_RESULT_PREOP'.

    • DDX19B|11269 ,  KANK4|163782 ,  SH2D3A|10045 ,  CA11|770 ,  COL23A1|91522 ,  ...

  • 774 genes correlated to 'DAYS_TO_PREOP_PSA'.

    • CCDC124|115098 ,  ZNF808|388558 ,  ARFRP1|10139 ,  MYPOP|339344 ,  HSD11B1L|374875 ,  ...

  • 1 gene correlated to 'PSA_VALUE'.

    • C9ORF85|138241

  • 4 genes correlated to 'DAYS_TO_PSA'.

    • HOOK2|29911 ,  PAN2|9924 ,  LOC100128842|100128842 ,  GTF2IRD2B|389524

  • No genes correlated to 'NUMBER.OF.LYMPH.NODES', and 'GLEASON_SCORE_SECONDARY'.

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
AGE Spearman correlation test N=1 older N=1 younger N=0
PATHOLOGY T STAGE Spearman correlation test N=19 higher stage N=5 lower stage N=14
PATHOLOGY N STAGE t test N=6 class1 N=1 class0 N=5
COMPLETENESS OF RESECTION ANOVA test N=1        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
GLEASON_SCORE_COMBINED Spearman correlation test N=60 higher score N=46 lower score N=14
GLEASON_SCORE_PRIMARY Spearman correlation test N=67 higher score N=18 lower score N=49
GLEASON_SCORE_SECONDARY Spearman correlation test   N=0        
GLEASON_SCORE Spearman correlation test N=105 higher score N=80 lower score N=25
PSA_RESULT_PREOP Spearman correlation test N=30 higher psa_result_preop N=2 lower psa_result_preop N=28
DAYS_TO_PREOP_PSA Spearman correlation test N=774 higher days_to_preop_psa N=353 lower days_to_preop_psa N=421
PSA_VALUE Spearman correlation test N=1 higher psa_value N=1 lower psa_value N=0
DAYS_TO_PSA Spearman correlation test N=4 higher days_to_psa N=0 lower days_to_psa N=4
Clinical variable #1: 'AGE'

One gene related to 'AGE'.

Table S1.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 60.28 (6.9)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'AGE' by Spearman correlation test

Table S2.  Get Full Table List of one gene significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
ADAP2|55803 0.3771 2.708e-08 0.000494

Figure S1.  Get High-res Image As an example, this figure shows the association of ADAP2|55803 to 'AGE'. P value = 2.71e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'PATHOLOGY.T.STAGE'

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

Table S3.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.57 (0.54)
  N
  2 92
  3 107
  4 5
     
  Significant markers N = 19
  pos. correlated 5
  neg. correlated 14
List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MT1H|4496 -0.3663 7.683e-08 0.0014
GMDS|2762 -0.36 1.23e-07 0.00225
FAM189A2|9413 -0.3592 1.32e-07 0.00241
OSGIN2|734 0.3567 1.635e-07 0.00299
CHRNA2|1135 -0.3518 2.466e-07 0.0045
FA2H|79152 -0.3501 2.861e-07 0.00522
KCNK6|9424 -0.3488 3.183e-07 0.00581
EPHX2|2053 -0.3435 4.896e-07 0.00894
GPR108|56927 -0.3361 8.926e-07 0.0163
PLA2G4F|255189 -0.3354 9.365e-07 0.0171

Figure S2.  Get High-res Image As an example, this figure shows the association of MT1H|4496 to 'PATHOLOGY.T.STAGE'. P value = 7.68e-08 with Spearman correlation analysis.

Clinical variable #3: 'PATHOLOGY.N.STAGE'

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

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Labels N
  class0 156
  class1 17
     
  Significant markers N = 6
  Higher in class1 1
  Higher in class0 5
List of 6 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S6.  Get Full Table List of 6 genes differentially expressed by 'PATHOLOGY.N.STAGE'

T(pos if higher in 'class1') ttestP Q AUC
NKX6-2|84504 -7.62 1.14e-09 2.08e-05 0.8951
PRTN3|5657 -7.96 1.471e-09 2.68e-05 0.814
CRHR2|1395 -9.24 8.274e-08 0.00151 0.9494
SLMO2|51012 5.64 1.003e-06 0.0183 0.759
LCNL1|401562 -5.75 2.191e-06 0.04 0.7526
FABP7|2173 -6.42 2.355e-06 0.043 0.7979

Figure S3.  Get High-res Image As an example, this figure shows the association of NKX6-2|84504 to 'PATHOLOGY.N.STAGE'. P value = 1.14e-09 with T-test analysis.

Clinical variable #4: 'COMPLETENESS.OF.RESECTION'

One gene related to 'COMPLETENESS.OF.RESECTION'.

Table S7.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 153
  R1 38
  RX 5
     
  Significant markers N = 1
List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S8.  Get Full Table List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
GLP2R|9340 8.781e-11 1.6e-06

Figure S4.  Get High-res Image As an example, this figure shows the association of GLP2R|9340 to 'COMPLETENESS.OF.RESECTION'. P value = 8.78e-11 with ANOVA analysis.

Clinical variable #5: 'NUMBER.OF.LYMPH.NODES'

No gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S9.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 0.18 (0.67)
  Value N
  0 154
  1 11
  2 2
  3 3
  6 1
     
  Significant markers N = 0
Clinical variable #6: 'GLEASON_SCORE_COMBINED'

60 genes related to 'GLEASON_SCORE_COMBINED'.

Table S10.  Basic characteristics of clinical feature: 'GLEASON_SCORE_COMBINED'

GLEASON_SCORE_COMBINED Mean (SD) 7.23 (0.77)
  Significant markers N = 60
  pos. correlated 46
  neg. correlated 14
List of top 10 genes significantly correlated to 'GLEASON_SCORE_COMBINED' by Spearman correlation test

Table S11.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_COMBINED' by Spearman correlation test

SpearmanCorr corrP Q
ZNF250|58500 0.3925 5.396e-09 9.85e-05
FAM72B|653820 0.3839 1.224e-08 0.000223
FA2H|79152 -0.3818 1.495e-08 0.000273
SH3RF2|153769 -0.3799 1.782e-08 0.000325
C12ORF48|55010 0.3782 2.093e-08 0.000382
FAM72A|729533 0.3858 2.998e-08 0.000547
CBX1|10951 0.3683 5.124e-08 0.000935
ARL6IP1|23204 0.3651 6.806e-08 0.00124
CCNE2|9134 0.3641 7.436e-08 0.00136
FMOD|2331 -0.3604 1.035e-07 0.00189

Figure S5.  Get High-res Image As an example, this figure shows the association of ZNF250|58500 to 'GLEASON_SCORE_COMBINED'. P value = 5.4e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #7: 'GLEASON_SCORE_PRIMARY'

67 genes related to 'GLEASON_SCORE_PRIMARY'.

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

GLEASON_SCORE_PRIMARY Mean (SD) 3.47 (0.57)
  Score N
  2 1
  3 115
  4 83
  5 7
     
  Significant markers N = 67
  pos. correlated 18
  neg. correlated 49
List of top 10 genes significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

Table S13.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

SpearmanCorr corrP Q
KANK4|163782 -0.4278 1.421e-10 2.6e-06
METTL6|131965 0.4221 2.628e-10 4.8e-06
SH3RF2|153769 -0.4202 3.235e-10 5.9e-06
C2|717 -0.3839 1.224e-08 0.000223
CD38|952 -0.3821 1.449e-08 0.000264
PIPOX|51268 -0.369 4.807e-08 0.000877
DPT|1805 -0.3673 5.638e-08 0.00103
FERMT1|55612 -0.3672 5.675e-08 0.00104
EDN3|1908 -0.3682 6.006e-08 0.0011
SGEF|26084 0.364 7.53e-08 0.00137

Figure S6.  Get High-res Image As an example, this figure shows the association of KANK4|163782 to 'GLEASON_SCORE_PRIMARY'. P value = 1.42e-10 with Spearman correlation analysis.

Clinical variable #8: 'GLEASON_SCORE_SECONDARY'

No gene related to 'GLEASON_SCORE_SECONDARY'.

Table S14.  Basic characteristics of clinical feature: 'GLEASON_SCORE_SECONDARY'

GLEASON_SCORE_SECONDARY Mean (SD) 3.77 (0.61)
  Score N
  3 68
  4 118
  5 20
     
  Significant markers N = 0
Clinical variable #9: 'GLEASON_SCORE'

105 genes related to 'GLEASON_SCORE'.

Table S15.  Basic characteristics of clinical feature: 'GLEASON_SCORE'

GLEASON_SCORE Mean (SD) 7.28 (0.8)
  Score N
  6 16
  7 143
  8 22
  9 23
  10 2
     
  Significant markers N = 105
  pos. correlated 80
  neg. correlated 25
List of top 10 genes significantly correlated to 'GLEASON_SCORE' by Spearman correlation test

Table S16.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
FA2H|79152 -0.4187 3.773e-10 6.89e-06
FAM72A|729533 0.412 2.634e-09 4.81e-05
C12ORF48|55010 0.3964 3.671e-09 6.7e-05
FMOD|2331 -0.3942 4.555e-09 8.32e-05
CCNE2|9134 0.3903 6.645e-09 0.000121
SH3RF2|153769 -0.3891 7.449e-09 0.000136
FAM72B|653820 0.3822 1.438e-08 0.000262
HMGB2|3148 0.3802 1.73e-08 0.000316
NUF2|83540 0.3747 2.885e-08 0.000526
CBX1|10951 0.3737 3.162e-08 0.000577

Figure S7.  Get High-res Image As an example, this figure shows the association of FA2H|79152 to 'GLEASON_SCORE'. P value = 3.77e-10 with Spearman correlation analysis.

Clinical variable #10: 'PSA_RESULT_PREOP'

30 genes related to 'PSA_RESULT_PREOP'.

Table S17.  Basic characteristics of clinical feature: 'PSA_RESULT_PREOP'

PSA_RESULT_PREOP Mean (SD) 10.26 (10)
  Significant markers N = 30
  pos. correlated 2
  neg. correlated 28
List of top 10 genes significantly correlated to 'PSA_RESULT_PREOP' by Spearman correlation test

Table S18.  Get Full Table List of top 10 genes significantly correlated to 'PSA_RESULT_PREOP' by Spearman correlation test

SpearmanCorr corrP Q
DDX19B|11269 -0.3945 5.283e-09 9.65e-05
KANK4|163782 -0.3939 5.601e-09 0.000102
SH2D3A|10045 -0.3666 6.914e-08 0.00126
CA11|770 -0.3663 7.137e-08 0.0013
COL23A1|91522 -0.364 8.708e-08 0.00159
SOX15|6665 -0.3605 1.183e-07 0.00216
ATCAY|85300 -0.3568 1.736e-07 0.00317
RAB6A|5870 0.3458 4.073e-07 0.00743
CDC42EP4|23580 -0.3416 5.743e-07 0.0105
PTPLA|9200 -0.3406 6.194e-07 0.0113

Figure S8.  Get High-res Image As an example, this figure shows the association of DDX19B|11269 to 'PSA_RESULT_PREOP'. P value = 5.28e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'DAYS_TO_PREOP_PSA'

774 genes related to 'DAYS_TO_PREOP_PSA'.

Table S19.  Basic characteristics of clinical feature: 'DAYS_TO_PREOP_PSA'

DAYS_TO_PREOP_PSA Mean (SD) -3.45 (96)
  Significant markers N = 774
  pos. correlated 353
  neg. correlated 421
List of top 10 genes significantly correlated to 'DAYS_TO_PREOP_PSA' by Spearman correlation test

Table S20.  Get Full Table List of top 10 genes significantly correlated to 'DAYS_TO_PREOP_PSA' by Spearman correlation test

SpearmanCorr corrP Q
CCDC124|115098 -0.4177 7.531e-10 1.37e-05
ZNF808|388558 0.4157 9.298e-10 1.7e-05
ARFRP1|10139 -0.4151 9.895e-10 1.81e-05
MYPOP|339344 -0.412 1.348e-09 2.46e-05
HSD11B1L|374875 -0.4108 1.526e-09 2.79e-05
RGPD4|285190 0.4081 1.994e-09 3.64e-05
ALKBH7|84266 -0.4068 2.276e-09 4.15e-05
JOSD2|126119 -0.4067 2.282e-09 4.17e-05
MARCH7|64844 0.4062 2.393e-09 4.37e-05
ATP5D|513 -0.4052 2.662e-09 4.86e-05

Figure S9.  Get High-res Image As an example, this figure shows the association of CCDC124|115098 to 'DAYS_TO_PREOP_PSA'. P value = 7.53e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #12: 'PSA_VALUE'

One gene related to 'PSA_VALUE'.

Table S21.  Basic characteristics of clinical feature: 'PSA_VALUE'

PSA_VALUE Mean (SD) 1.35 (4.3)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'PSA_VALUE' by Spearman correlation test

Table S22.  Get Full Table List of one gene significantly correlated to 'PSA_VALUE' by Spearman correlation test

SpearmanCorr corrP Q
C9ORF85|138241 0.3454 2.498e-06 0.0456

Figure S10.  Get High-res Image As an example, this figure shows the association of C9ORF85|138241 to 'PSA_VALUE'. P value = 2.5e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #13: 'DAYS_TO_PSA'

4 genes related to 'DAYS_TO_PSA'.

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

DAYS_TO_PSA Mean (SD) 574.9 (550)
  Significant markers N = 4
  pos. correlated 0
  neg. correlated 4
List of 4 genes significantly correlated to 'DAYS_TO_PSA' by Spearman correlation test

Table S24.  Get Full Table List of 4 genes significantly correlated to 'DAYS_TO_PSA' by Spearman correlation test

SpearmanCorr corrP Q
HOOK2|29911 -0.4676 2.835e-11 5.18e-07
PAN2|9924 -0.383 9.522e-08 0.00174
LOC100128842|100128842 -0.3563 7.945e-07 0.0145
GTF2IRD2B|389524 -0.3435 2.067e-06 0.0377

Figure S11.  Get High-res Image As an example, this figure shows the association of HOOK2|29911 to 'DAYS_TO_PSA'. P value = 2.83e-11 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

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

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

  • Number of patients = 206

  • Number of genes = 18258

  • Number of clinical features = 13

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

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

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

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] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] 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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