Correlation between miRseq expression and clinical features
Prostate Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C11R6P9J
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C11R6P9J
Overview
Introduction

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

Summary

Testing the association between 471 miRs and 13 clinical features across 272 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one miRs.

  • 3 miRs correlated to 'AGE'.

    • HSA-MIR-627 ,  HSA-MIR-570 ,  HSA-MIR-3922

  • 16 miRs correlated to 'PATHOLOGY.T.STAGE'.

    • HSA-MIR-3676 ,  HSA-MIR-451 ,  HSA-MIR-30A ,  HSA-MIR-133A-1 ,  HSA-MIR-486 ,  ...

  • 7 miRs correlated to 'PATHOLOGY.N.STAGE'.

    • HSA-MIR-378 ,  HSA-MIR-133A-1 ,  HSA-MIR-221 ,  HSA-MIR-222 ,  HSA-MIR-1-2 ,  ...

  • 1 miR correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-143

  • 8 miRs correlated to 'NUMBER.OF.LYMPH.NODES'.

    • HSA-MIR-133A-1 ,  HSA-MIR-221 ,  HSA-MIR-378 ,  HSA-MIR-222 ,  HSA-MIR-1-2 ,  ...

  • 25 miRs correlated to 'GLEASON_SCORE_COMBINED'.

    • HSA-MIR-1-2 ,  HSA-MIR-133B ,  HSA-MIR-133A-1 ,  HSA-MIR-592 ,  HSA-MIR-221 ,  ...

  • 25 miRs correlated to 'GLEASON_SCORE_PRIMARY'.

    • HSA-MIR-221 ,  HSA-MIR-1-2 ,  HSA-MIR-222 ,  HSA-MIR-133A-1 ,  HSA-MIR-891A ,  ...

  • 26 miRs correlated to 'GLEASON_SCORE'.

    • HSA-MIR-1-2 ,  HSA-MIR-217 ,  HSA-MIR-221 ,  HSA-MIR-133B ,  HSA-MIR-592 ,  ...

  • 11 miRs correlated to 'PSA_RESULT_PREOP'.

    • HSA-MIR-15B ,  HSA-MIR-145 ,  HSA-MIR-130A ,  HSA-MIR-133A-1 ,  HSA-MIR-205 ,  ...

  • 1 miR correlated to 'PSA_VALUE'.

    • HSA-MIR-450A-1

  • No miRs correlated to 'COMPLETENESS.OF.RESECTION', 'GLEASON_SCORE_SECONDARY', 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 miRs that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.

Clinical feature Statistical test Significant miRs Associated with                 Associated with
AGE Spearman correlation test N=3 older N=3 younger N=0
PATHOLOGY T STAGE Spearman correlation test N=16 higher stage N=0 lower stage N=16
PATHOLOGY N STAGE Wilcoxon test N=7 class1 N=7 class0 N=0
HISTOLOGICAL TYPE Wilcoxon test N=1 prostate adenocarcinoma acinar type N=1 prostate adenocarcinoma other subtype N=0
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=8 higher number.of.lymph.nodes N=0 lower number.of.lymph.nodes N=8
GLEASON_SCORE_COMBINED Spearman correlation test N=25 higher score N=9 lower score N=16
GLEASON_SCORE_PRIMARY Spearman correlation test N=25 higher score N=5 lower score N=20
GLEASON_SCORE_SECONDARY Spearman correlation test   N=0        
GLEASON_SCORE Spearman correlation test N=26 higher score N=10 lower score N=16
PSA_RESULT_PREOP Spearman correlation test N=11 higher psa_result_preop N=2 lower psa_result_preop N=9
PSA_VALUE Spearman correlation test N=1 higher psa_value N=0 lower psa_value N=1
RACE Kruskal-Wallis test   N=0        
Clinical variable #1: 'AGE'

3 miRs related to 'AGE'.

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

AGE Mean (SD) 60.38 (7)
  Significant markers N = 3
  pos. correlated 3
  neg. correlated 0
List of 3 miRs differentially expressed by 'AGE'

Table S2.  Get Full Table List of 3 miRs significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-627 0.2766 9.087e-06 0.00428
HSA-MIR-570 0.2709 0.000255 0.12
HSA-MIR-3922 0.3141 0.0005035 0.236
Clinical variable #2: 'PATHOLOGY.T.STAGE'

16 miRs related to 'PATHOLOGY.T.STAGE'.

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

PATHOLOGY.T.STAGE Mean (SD) 2.54 (0.53)
  N
  2 127
  3 139
  4 4
     
  Significant markers N = 16
  pos. correlated 0
  neg. correlated 16
List of top 10 miRs differentially expressed by 'PATHOLOGY.T.STAGE'

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

SpearmanCorr corrP Q
HSA-MIR-3676 -0.3556 2.073e-09 9.76e-07
HSA-MIR-451 -0.314 1.372e-07 6.45e-05
HSA-MIR-30A -0.3041 3.496e-07 0.000164
HSA-MIR-133A-1 -0.2923 1.016e-06 0.000475
HSA-MIR-486 -0.267 8.699e-06 0.00406
HSA-MIR-29C -0.2505 3.131e-05 0.0146
HSA-MIR-1468 -0.2457 4.465e-05 0.0208
HSA-MIR-598 -0.2413 6.174e-05 0.0286
HSA-MIR-222 -0.2349 9.761e-05 0.0452
HSA-MIR-145 -0.2322 0.0001179 0.0545
Clinical variable #3: 'PATHOLOGY.N.STAGE'

7 miRs related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE Labels N
  class0 203
  class1 23
     
  Significant markers N = 7
  Higher in class1 7
  Higher in class0 0
List of 7 miRs differentially expressed by 'PATHOLOGY.N.STAGE'

Table S6.  Get Full Table List of 7 miRs differentially expressed by 'PATHOLOGY.N.STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
HSA-MIR-378 1162 8.027e-05 0.0378 0.7511
HSA-MIR-133A-1 1166 8.489e-05 0.0399 0.7503
HSA-MIR-221 1167 8.609e-05 0.0404 0.7501
HSA-MIR-222 1238 0.0002261 0.106 0.7348
HSA-MIR-1-2 1245 0.000248 0.116 0.7333
HSA-MIR-133B 1305 0.0005822 0.271 0.7191
HSA-MIR-133A-2 1285 0.0005836 0.271 0.7192
Clinical variable #4: 'HISTOLOGICAL.TYPE'

One miR related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  PROSTATE ADENOCARCINOMA OTHER SUBTYPE 6
  PROSTATE ADENOCARCINOMA ACINAR TYPE 266
     
  Significant markers N = 1
  Higher in PROSTATE ADENOCARCINOMA ACINAR TYPE 1
  Higher in PROSTATE ADENOCARCINOMA OTHER SUBTYPE 0
List of one miR differentially expressed by 'HISTOLOGICAL.TYPE'

Table S8.  Get Full Table List of one miR differentially expressed by 'HISTOLOGICAL.TYPE'

W(pos if higher in 'PROSTATE ADENOCARCINOMA ACINAR TYPE') wilcoxontestP Q AUC
HSA-MIR-143 c("1461", "0.0005075") c("1461", "0.0005075") 0.206 0.9154
Clinical variable #5: 'COMPLETENESS.OF.RESECTION'

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

Table S9.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 193
  R1 57
  R2 3
  RX 6
     
  Significant markers N = 0
Clinical variable #6: 'NUMBER.OF.LYMPH.NODES'

8 miRs related to 'NUMBER.OF.LYMPH.NODES'.

Table S10.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 0.23 (1.2)
  Significant markers N = 8
  pos. correlated 0
  neg. correlated 8
List of 8 miRs differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S11.  Get Full Table List of 8 miRs significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-133A-1 -0.2646 6.097e-05 0.0287
HSA-MIR-221 -0.2642 6.224e-05 0.0293
HSA-MIR-378 -0.2641 6.278e-05 0.0294
HSA-MIR-222 -0.2479 0.0001782 0.0834
HSA-MIR-1-2 -0.2474 0.0001835 0.0857
HSA-MIR-133A-2 -0.2386 0.0003554 0.166
HSA-MIR-133B -0.2366 0.0003641 0.169
HSA-MIR-139 -0.2266 0.0006328 0.294
Clinical variable #7: 'GLEASON_SCORE_COMBINED'

25 miRs related to 'GLEASON_SCORE_COMBINED'.

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

GLEASON_SCORE_COMBINED Mean (SD) 7.29 (0.81)
  Significant markers N = 25
  pos. correlated 9
  neg. correlated 16
List of top 10 miRs differentially expressed by 'GLEASON_SCORE_COMBINED'

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

SpearmanCorr corrP Q
HSA-MIR-1-2 -0.3744 1.777e-10 8.37e-08
HSA-MIR-133B -0.3435 6.806e-09 3.2e-06
HSA-MIR-133A-1 -0.3272 3.298e-08 1.55e-05
HSA-MIR-592 0.3488 5.568e-08 2.61e-05
HSA-MIR-221 -0.319 7.554e-08 3.53e-05
HSA-MIR-217 0.316 1.015e-07 4.73e-05
HSA-MIR-133A-2 -0.3089 2.605e-07 0.000121
HSA-MIR-222 -0.2831 2.083e-06 0.000966
HSA-MIR-3676 -0.2839 2.125e-06 0.000984
HSA-MIR-378C -0.2683 7.236e-06 0.00334
Clinical variable #8: 'GLEASON_SCORE_PRIMARY'

25 miRs related to 'GLEASON_SCORE_PRIMARY'.

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

GLEASON_SCORE_PRIMARY Mean (SD) 3.49 (0.56)
  Score N
  2 1
  3 145
  4 118
  5 8
     
  Significant markers N = 25
  pos. correlated 5
  neg. correlated 20
List of top 10 miRs differentially expressed by 'GLEASON_SCORE_PRIMARY'

Table S15.  Get Full Table List of top 10 miRs significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-221 -0.3741 1.836e-10 8.65e-08
HSA-MIR-1-2 -0.35 2.96e-09 1.39e-06
HSA-MIR-222 -0.3233 4.91e-08 2.3e-05
HSA-MIR-133A-1 -0.3233 4.92e-08 2.3e-05
HSA-MIR-891A -0.3234 8.085e-08 3.78e-05
HSA-MIR-133B -0.3107 1.87e-07 8.71e-05
HSA-MIR-184 -0.3276 3.739e-07 0.000174
HSA-MIR-3676 -0.3015 4.439e-07 0.000206
HSA-MIR-378C -0.2979 5.604e-07 0.000259
HSA-MIR-133A-2 -0.2879 1.713e-06 0.000792
Clinical variable #9: 'GLEASON_SCORE_SECONDARY'

No miR related to 'GLEASON_SCORE_SECONDARY'.

Table S16.  Basic characteristics of clinical feature: 'GLEASON_SCORE_SECONDARY'

GLEASON_SCORE_SECONDARY Mean (SD) 3.8 (0.62)
  Score N
  3 85
  4 156
  5 31
     
  Significant markers N = 0
Clinical variable #10: 'GLEASON_SCORE'

26 miRs related to 'GLEASON_SCORE'.

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

GLEASON_SCORE Mean (SD) 7.33 (0.83)
  Score N
  6 23
  7 176
  8 35
  9 37
  10 1
     
  Significant markers N = 26
  pos. correlated 10
  neg. correlated 16
List of top 10 miRs differentially expressed by 'GLEASON_SCORE'

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

SpearmanCorr corrP Q
HSA-MIR-1-2 -0.3443 5.489e-09 2.59e-06
HSA-MIR-217 0.3307 2.303e-08 1.08e-05
HSA-MIR-221 -0.3268 3.461e-08 1.62e-05
HSA-MIR-133B -0.3129 1.522e-07 7.12e-05
HSA-MIR-592 0.3341 2.109e-07 9.85e-05
HSA-MIR-133A-1 -0.3073 2.342e-07 0.000109
HSA-MIR-222 -0.2922 9.373e-07 0.000436
HSA-MIR-3676 -0.2901 1.238e-06 0.000574
HSA-MIR-133A-2 -0.2848 2.247e-06 0.00104
HSA-MIR-891A -0.2781 4.65e-06 0.00215
Clinical variable #11: 'PSA_RESULT_PREOP'

11 miRs related to 'PSA_RESULT_PREOP'.

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

PSA_RESULT_PREOP Mean (SD) 10.48 (11)
  Significant markers N = 11
  pos. correlated 2
  neg. correlated 9
List of top 10 miRs differentially expressed by 'PSA_RESULT_PREOP'

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

SpearmanCorr corrP Q
HSA-MIR-15B 0.2708 6.378e-06 0.003
HSA-MIR-145 -0.2408 6.409e-05 0.0301
HSA-MIR-130A -0.2295 0.0001426 0.0669
HSA-MIR-133A-1 -0.2279 0.0001583 0.0741
HSA-MIR-205 -0.2255 0.000192 0.0897
HSA-MIR-222 -0.2242 0.0002033 0.0947
HSA-MIR-224 -0.2215 0.0002505 0.116
HSA-MIR-1-2 -0.2191 0.0002852 0.132
HSA-MIR-221 -0.2131 0.0004231 0.196
HSA-MIR-3647 -0.2131 0.0004314 0.199
Clinical variable #12: 'PSA_VALUE'

One miR related to 'PSA_VALUE'.

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

PSA_VALUE Mean (SD) 1.1 (3.9)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one miR differentially expressed by 'PSA_VALUE'

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

SpearmanCorr corrP Q
HSA-MIR-450A-1 -0.2588 0.0001068 0.0503
Clinical variable #13: 'RACE'

No miR related to 'RACE'.

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

RACE Labels N
  ASIAN 2
  BLACK OR AFRICAN AMERICAN 7
  WHITE 146
     
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = PRAD-TP.miRseq_RPKM_log2.txt

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

  • Number of patients = 272

  • Number of miRs = 471

  • 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