Correlation between mRNAseq expression and clinical features
Prostate Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C15H7F2Q
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/C15H7F2Q
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 18250 genes and 13 clinical features across 268 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 2 genes correlated to 'AGE'.

    • ADAP2|55803 ,  MNX1|3110

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

    • CHRNA2|1135 ,  FAM189A2|9413 ,  GPR108|56927 ,  EPHX2|2053 ,  OSGIN2|734 ,  ...

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

    • SLC2A4|6517 ,  LY6G6D|58530 ,  CTNNAL1|8727 ,  COL23A1|91522

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

    • SLC2A4|6517 ,  LY6G6D|58530 ,  COL23A1|91522 ,  SNCG|6623 ,  CTNNAL1|8727 ,  ...

  • 461 genes correlated to 'GLEASON_SCORE_COMBINED'.

    • FAM72B|653820 ,  SH3RF2|153769 ,  FAM72D|728833 ,  NUF2|83540 ,  CBX1|10951 ,  ...

  • 439 genes correlated to 'GLEASON_SCORE_PRIMARY'.

    • SH3RF2|153769 ,  SLC22A3|6581 ,  C2|717 ,  CTHRC1|115908 ,  DPT|1805 ,  ...

  • 3 genes correlated to 'GLEASON_SCORE_SECONDARY'.

    • TMEFF1|8577 ,  GK|2710 ,  SEC61A2|55176

  • 495 genes correlated to 'GLEASON_SCORE'.

    • FAM72B|653820 ,  SH3RF2|153769 ,  FAM72D|728833 ,  NUF2|83540 ,  FAM72A|729533 ,  ...

  • 103 genes correlated to 'PSA_RESULT_PREOP'.

    • KANK4|163782 ,  COL23A1|91522 ,  RAB6A|5870 ,  TUBA4A|7277 ,  SH2D3A|10045 ,  ...

  • 5 genes correlated to 'PSA_VALUE'.

    • C9ORF85|138241 ,  SOD3|6649 ,  FAM108B1|51104 ,  FXYD1|5348 ,  CST3|1471

  • No genes correlated to 'HISTOLOGICAL.TYPE', 'COMPLETENESS.OF.RESECTION', and 'RACE'.

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
AGE Spearman correlation test N=2 older N=2 younger N=0
PATHOLOGY T STAGE Spearman correlation test N=278 higher stage N=131 lower stage N=147
PATHOLOGY N STAGE Wilcoxon test N=4 class1 N=4 class0 N=0
HISTOLOGICAL TYPE Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=6 higher number.of.lymph.nodes N=1 lower number.of.lymph.nodes N=5
GLEASON_SCORE_COMBINED Spearman correlation test N=461 higher score N=311 lower score N=150
GLEASON_SCORE_PRIMARY Spearman correlation test N=439 higher score N=185 lower score N=254
GLEASON_SCORE_SECONDARY Spearman correlation test N=3 higher score N=3 lower score N=0
GLEASON_SCORE Spearman correlation test N=495 higher score N=334 lower score N=161
PSA_RESULT_PREOP Spearman correlation test N=103 higher psa_result_preop N=28 lower psa_result_preop N=75
PSA_VALUE Spearman correlation test N=5 higher psa_value N=2 lower psa_value N=3
RACE Kruskal-Wallis test   N=0        
Clinical variable #1: 'AGE'

2 genes related to 'AGE'.

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

AGE Mean (SD) 60.2 (7)
  Significant markers N = 2
  pos. correlated 2
  neg. correlated 0
List of 2 genes differentially expressed by 'AGE'

Table S2.  Get Full Table List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
ADAP2|55803 0.3172 1.319e-07 0.00241
MNX1|3110 0.2673 1.198e-05 0.219
Clinical variable #2: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.54 (0.54)
  N
  2 127
  3 134
  4 5
     
  Significant markers N = 278
  pos. correlated 131
  neg. correlated 147
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

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

SpearmanCorr corrP Q
CHRNA2|1135 -0.386 7.043e-11 1.29e-06
FAM189A2|9413 -0.3849 7.997e-11 1.46e-06
GPR108|56927 -0.3705 4.461e-10 8.14e-06
EPHX2|2053 -0.366 7.466e-10 1.36e-05
OSGIN2|734 0.3515 3.747e-09 6.84e-05
GMDS|2762 -0.3514 3.774e-09 6.89e-05
PICK1|9463 -0.3485 5.182e-09 9.45e-05
MYBPC1|4604 -0.3484 5.236e-09 9.55e-05
MYT1|4661 0.3586 5.712e-09 0.000104
RAD21|5885 0.3446 7.86e-09 0.000143
Clinical variable #3: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Labels N
  class0 198
  class1 24
     
  Significant markers N = 4
  Higher in class1 4
  Higher in class0 0
List of 4 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S6.  Get Full Table List of 4 genes differentially expressed by 'PATHOLOGY.N.STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
SLC2A4|6517 1036 6.557e-06 0.12 0.782
LY6G6D|58530 672 1.106e-05 0.202 0.8067
CTNNAL1|8727 3672 1.304e-05 0.238 0.7727
COL23A1|91522 1091 1.543e-05 0.281 0.7704
Clinical variable #4: 'HISTOLOGICAL.TYPE'

No gene related to 'HISTOLOGICAL.TYPE'.

Table S7.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  PROSTATE ADENOCARCINOMA OTHER SUBTYPE 5
  PROSTATE ADENOCARCINOMA ACINAR TYPE 263
     
  Significant markers N = 0
Clinical variable #5: 'COMPLETENESS.OF.RESECTION'

No gene related to 'COMPLETENESS.OF.RESECTION'.

Table S8.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 190
  R1 56
  R2 3
  RX 6
     
  Significant markers N = 0
Clinical variable #6: 'NUMBER.OF.LYMPH.NODES'

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

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

NUMBER.OF.LYMPH.NODES Mean (SD) 0.24 (1.2)
  Significant markers N = 6
  pos. correlated 1
  neg. correlated 5
List of 6 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S10.  Get Full Table List of 6 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
SLC2A4|6517 -0.3061 3.724e-06 0.068
LY6G6D|58530 -0.3133 6.26e-06 0.114
COL23A1|91522 -0.2958 8.104e-06 0.148
SNCG|6623 -0.2916 1.099e-05 0.201
CTNNAL1|8727 0.29 1.238e-05 0.226
PYGM|5837 -0.287 1.528e-05 0.279
Clinical variable #7: 'GLEASON_SCORE_COMBINED'

461 genes related to 'GLEASON_SCORE_COMBINED'.

Table S11.  Basic characteristics of clinical feature: 'GLEASON_SCORE_COMBINED'

GLEASON_SCORE_COMBINED Mean (SD) 7.29 (0.81)
  Significant markers N = 461
  pos. correlated 311
  neg. correlated 150
List of top 10 genes differentially expressed by 'GLEASON_SCORE_COMBINED'

Table S12.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_COMBINED' by Spearman correlation test

SpearmanCorr corrP Q
FAM72B|653820 0.4259 3.106e-13 5.67e-09
SH3RF2|153769 -0.4027 7.211e-12 1.32e-07
FAM72D|728833 0.3945 2.051e-11 3.74e-07
NUF2|83540 0.3938 2.259e-11 4.12e-07
CBX1|10951 0.3809 1.103e-10 2.01e-06
CENPE|1062 0.3798 1.27e-10 2.32e-06
CENPA|1058 0.3766 2.007e-10 3.66e-06
FAM72A|729533 0.388 2.086e-10 3.81e-06
GLB1L3|112937 -0.3743 2.652e-10 4.84e-06
NEK2|4751 0.3736 2.875e-10 5.24e-06
Clinical variable #8: 'GLEASON_SCORE_PRIMARY'

439 genes related to 'GLEASON_SCORE_PRIMARY'.

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

GLEASON_SCORE_PRIMARY Mean (SD) 3.49 (0.57)
  Score N
  2 1
  3 144
  4 114
  5 9
     
  Significant markers N = 439
  pos. correlated 185
  neg. correlated 254
List of top 10 genes differentially expressed by 'GLEASON_SCORE_PRIMARY'

Table S14.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

SpearmanCorr corrP Q
SH3RF2|153769 -0.4299 1.773e-13 3.24e-09
SLC22A3|6581 -0.411 2.64e-12 4.82e-08
C2|717 -0.4094 2.958e-12 5.4e-08
CTHRC1|115908 0.4012 8.745e-12 1.6e-07
DPT|1805 -0.3956 1.783e-11 3.25e-07
MMP11|4320 0.3905 3.424e-11 6.25e-07
CD38|952 -0.3888 4.201e-11 7.66e-07
IGSF1|3547 -0.3891 5.703e-11 1.04e-06
ITGBL1|9358 0.384 7.565e-11 1.38e-06
METTL6|131965 0.3796 1.29e-10 2.35e-06
Clinical variable #9: 'GLEASON_SCORE_SECONDARY'

3 genes related to 'GLEASON_SCORE_SECONDARY'.

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

GLEASON_SCORE_SECONDARY Mean (SD) 3.8 (0.62)
  Score N
  3 83
  4 155
  5 30
     
  Significant markers N = 3
  pos. correlated 3
  neg. correlated 0
List of 3 genes differentially expressed by 'GLEASON_SCORE_SECONDARY'

Table S16.  Get Full Table List of 3 genes significantly correlated to 'GLEASON_SCORE_SECONDARY' by Spearman correlation test

SpearmanCorr corrP Q
TMEFF1|8577 0.2685 8.317e-06 0.152
GK|2710 0.2641 1.176e-05 0.215
SEC61A2|55176 0.264 1.188e-05 0.217
Clinical variable #10: 'GLEASON_SCORE'

495 genes related to 'GLEASON_SCORE'.

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

GLEASON_SCORE Mean (SD) 7.33 (0.83)
  Score N
  6 21
  7 177
  8 33
  9 35
  10 2
     
  Significant markers N = 495
  pos. correlated 334
  neg. correlated 161
List of top 10 genes differentially expressed by 'GLEASON_SCORE'

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

SpearmanCorr corrP Q
FAM72B|653820 0.4123 2.024e-12 3.69e-08
SH3RF2|153769 -0.3999 1.033e-11 1.88e-07
FAM72D|728833 0.3976 1.382e-11 2.52e-07
NUF2|83540 0.3955 1.807e-11 3.3e-07
FAM72A|729533 0.4052 2.675e-11 4.88e-07
CENPE|1062 0.3904 3.436e-11 6.27e-07
FA2H|79152 -0.3887 4.28e-11 7.81e-07
FMOD|2331 -0.3812 1.071e-10 1.95e-06
CBX1|10951 0.3801 1.221e-10 2.23e-06
GLB1L3|112937 -0.3802 1.312e-10 2.39e-06
Clinical variable #11: 'PSA_RESULT_PREOP'

103 genes related to 'PSA_RESULT_PREOP'.

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

PSA_RESULT_PREOP Mean (SD) 10.11 (10)
  Significant markers N = 103
  pos. correlated 28
  neg. correlated 75
List of top 10 genes differentially expressed by 'PSA_RESULT_PREOP'

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

SpearmanCorr corrP Q
KANK4|163782 -0.3645 9.497e-10 1.73e-05
COL23A1|91522 -0.3385 1.49e-08 0.000272
RAB6A|5870 0.3239 6.53e-08 0.00119
TUBA4A|7277 -0.3189 1.057e-07 0.00193
SH2D3A|10045 -0.3132 1.832e-07 0.00334
CA11|770 -0.3114 2.173e-07 0.00396
FLJ39739|388685 0.3091 2.82e-07 0.00515
DDX19B|11269 -0.3079 3.013e-07 0.0055
RAB10|10890 0.3079 3.02e-07 0.00551
ATCAY|85300 -0.3057 3.885e-07 0.00709
Clinical variable #12: 'PSA_VALUE'

5 genes related to 'PSA_VALUE'.

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

PSA_VALUE Mean (SD) 1.09 (3.9)
  Significant markers N = 5
  pos. correlated 2
  neg. correlated 3
List of 5 genes differentially expressed by 'PSA_VALUE'

Table S22.  Get Full Table List of 5 genes significantly correlated to 'PSA_VALUE' by Spearman correlation test

SpearmanCorr corrP Q
C9ORF85|138241 0.3126 1.815e-06 0.0331
SOD3|6649 -0.3043 3.5e-06 0.0639
FAM108B1|51104 0.2996 5.018e-06 0.0916
FXYD1|5348 -0.2987 5.351e-06 0.0976
CST3|1471 -0.2857 1.401e-05 0.256
Clinical variable #13: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 2
  BLACK OR AFRICAN AMERICAN 7
  WHITE 147
     
  Significant markers N = 0
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 = 268

  • Number of genes = 18250

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