Correlation between miRseq expression and clinical features
Prostate Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
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/C1K0735G
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 469 miRs and 14 clinical features across 363 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one miRs.

  • 1 miR correlated to 'AGE'.

    • HSA-MIR-627

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

    • HSA-MIR-3676 ,  HSA-MIR-133A-1 ,  HSA-MIR-30A ,  HSA-MIR-222 ,  HSA-MIR-221 ,  ...

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

    • HSA-MIR-133A-2 ,  HSA-MIR-3676 ,  HSA-MIR-221 ,  HSA-MIR-133B ,  HSA-MIR-217 ,  ...

  • 1 miR correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-10A

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

    • HSA-MIR-3676

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

    • HSA-MIR-133A-2 ,  HSA-MIR-221 ,  HSA-MIR-133B ,  HSA-MIR-3676 ,  HSA-MIR-217 ,  ...

  • 43 miRs correlated to 'GLEASON_SCORE_COMBINED'.

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

  • 43 miRs correlated to 'GLEASON_SCORE_PRIMARY'.

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

  • 6 miRs correlated to 'GLEASON_SCORE_SECONDARY'.

    • HSA-MIR-133B ,  HSA-MIR-592 ,  HSA-MIR-217 ,  HSA-MIR-133A-2 ,  HSA-MIR-514-3 ,  ...

  • 43 miRs correlated to 'GLEASON_SCORE'.

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

  • 17 miRs correlated to 'PSA_RESULT_PREOP'.

    • HSA-MIR-145 ,  HSA-MIR-222 ,  HSA-MIR-221 ,  HSA-MIR-133A-1 ,  HSA-MIR-15B ,  ...

  • No miRs correlated to 'Time to Death', 'PSA_VALUE', 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
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=1 older N=1 younger N=0
PATHOLOGY T STAGE Spearman correlation test N=34 higher stage N=2 lower stage N=32
PATHOLOGY N STAGE Wilcoxon test N=11 class1 N=11 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=1        
NUMBER OF LYMPH NODES Spearman correlation test N=11 higher number.of.lymph.nodes N=2 lower number.of.lymph.nodes N=9
GLEASON_SCORE_COMBINED Spearman correlation test N=43 higher score N=20 lower score N=23
GLEASON_SCORE_PRIMARY Spearman correlation test N=43 higher score N=16 lower score N=27
GLEASON_SCORE_SECONDARY Spearman correlation test N=6 higher score N=3 lower score N=3
GLEASON_SCORE Spearman correlation test N=43 higher score N=17 lower score N=26
PSA_RESULT_PREOP Spearman correlation test N=17 higher psa_result_preop N=1 lower psa_result_preop N=16
PSA_VALUE Spearman correlation test   N=0        
RACE Kruskal-Wallis test   N=0        
Clinical variable #1: 'Time to Death'

No miR related to 'Time to Death'.

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

Time to Death Duration (Months) 0.3-151.4 (median=23.9)
  censored N = 355
  death N = 6
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

One miR related to 'AGE'.

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

AGE Mean (SD) 60.84 (7)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one miR differentially expressed by 'AGE'

Table S3.  Get Full Table List of one miR significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-627 0.2473 5.454e-06 0.00256
Clinical variable #3: 'PATHOLOGY.T.STAGE'

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

Table S4.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.6 (0.51)
  N
  2 149
  3 208
  4 4
     
  Significant markers N = 34
  pos. correlated 2
  neg. correlated 32
List of top 10 miRs differentially expressed by 'PATHOLOGY.T.STAGE'

Table S5.  Get Full Table List of top 10 miRs significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-3676 -0.3284 2.269e-10 1.06e-07
HSA-MIR-133A-1 -0.3026 4.425e-09 2.07e-06
HSA-MIR-30A -0.2952 1.083e-08 5.06e-06
HSA-MIR-222 -0.2829 4.517e-08 2.1e-05
HSA-MIR-221 -0.2646 3.372e-07 0.000157
HSA-MIR-145 -0.2412 3.566e-06 0.00165
HSA-MIR-574 -0.2405 3.821e-06 0.00177
HSA-MIR-133B -0.238 5.107e-06 0.00236
HSA-MIR-378C -0.2372 5.205e-06 0.0024
HSA-MIR-451 -0.2369 5.356e-06 0.00246
Clinical variable #4: 'PATHOLOGY.N.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Labels N
  class0 263
  class1 44
     
  Significant markers N = 11
  Higher in class1 11
  Higher in class0 0
List of top 10 miRs differentially expressed by 'PATHOLOGY.N.STAGE'

Table S7.  Get Full Table List of top 10 miRs differentially expressed by 'PATHOLOGY.N.STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
HSA-MIR-133A-2 3276 9.361e-06 0.00439 0.7092
HSA-MIR-3676 3417 2.46e-05 0.0115 0.699
HSA-MIR-221 3500 2.745e-05 0.0128 0.6975
HSA-MIR-133B 3552 4.657e-05 0.0217 0.6919
HSA-MIR-217 7870 0.0001318 0.0613 0.6801
HSA-MIR-133A-1 3739 0.0001733 0.0804 0.6769
HSA-MIR-378 3743 0.0001784 0.0826 0.6765
HSA-MIR-1-2 3750 0.0001878 0.0867 0.6759
HSA-MIR-222 3788 0.0002471 0.114 0.6727
HSA-MIR-21 7762 0.0002891 0.133 0.6708
Clinical variable #5: 'HISTOLOGICAL.TYPE'

One miR related to 'HISTOLOGICAL.TYPE'.

Table S8.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  PROSTATE ADENOCARCINOMA OTHER SUBTYPE 14
  PROSTATE ADENOCARCINOMA ACINAR TYPE 349
     
  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 S9.  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-10A c("1129", "0.0006452") c("1129", "0.0006452") 0.299 0.7689
Clinical variable #6: 'COMPLETENESS.OF.RESECTION'

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

Table S10.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 242
  R1 91
  R2 5
  RX 11
     
  Significant markers N = 1
List of one miR differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S11.  Get Full Table List of one miR differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
HSA-MIR-3676 0.0001826 0.0857
Clinical variable #7: 'NUMBER.OF.LYMPH.NODES'

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

Table S12.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 0.34 (1.3)
  Significant markers N = 11
  pos. correlated 2
  neg. correlated 9
List of top 10 miRs differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S13.  Get Full Table List of top 10 miRs significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-133A-2 -0.266 3.467e-06 0.00163
HSA-MIR-221 -0.2483 1.226e-05 0.00574
HSA-MIR-133B -0.2435 1.881e-05 0.00878
HSA-MIR-3676 -0.2391 3.025e-05 0.0141
HSA-MIR-217 0.2285 5.963e-05 0.0277
HSA-MIR-133A-1 -0.2202 0.000111 0.0515
HSA-MIR-1-2 -0.2186 0.0001255 0.0581
HSA-MIR-21 0.2163 0.0001479 0.0683
HSA-MIR-222 -0.2149 0.0001632 0.0752
HSA-MIR-378 -0.2106 0.0002226 0.102
Clinical variable #8: 'GLEASON_SCORE_COMBINED'

43 miRs related to 'GLEASON_SCORE_COMBINED'.

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

GLEASON_SCORE_COMBINED Mean (SD) 7.45 (0.92)
  Significant markers N = 43
  pos. correlated 20
  neg. correlated 23
List of top 10 miRs differentially expressed by 'GLEASON_SCORE_COMBINED'

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

SpearmanCorr corrP Q
HSA-MIR-133B -0.4192 8.526e-17 4e-14
HSA-MIR-133A-2 -0.4039 2.298e-15 1.08e-12
HSA-MIR-1-2 -0.3747 1.532e-13 7.15e-11
HSA-MIR-217 0.3727 2.094e-13 9.76e-11
HSA-MIR-221 -0.3546 3.405e-12 1.58e-09
HSA-MIR-592 0.3691 1.665e-11 7.72e-09
HSA-MIR-133A-1 -0.3381 3.686e-11 1.71e-08
HSA-MIR-21 0.3222 3.243e-10 1.5e-07
HSA-MIR-222 -0.3217 3.473e-10 1.6e-07
HSA-MIR-3676 -0.3161 1e-09 4.6e-07
Clinical variable #9: 'GLEASON_SCORE_PRIMARY'

43 miRs related to 'GLEASON_SCORE_PRIMARY'.

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

GLEASON_SCORE_PRIMARY Mean (SD) 3.6 (0.61)
  Score N
  2 1
  3 167
  4 172
  5 23
     
  Significant markers N = 43
  pos. correlated 16
  neg. correlated 27
List of top 10 miRs differentially expressed by 'GLEASON_SCORE_PRIMARY'

Table S17.  Get Full Table List of top 10 miRs significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-221 -0.3691 3.676e-13 1.72e-10
HSA-MIR-133B -0.3694 4.096e-13 1.92e-10
HSA-MIR-1-2 -0.3548 3.287e-12 1.54e-09
HSA-MIR-133A-2 -0.3552 5.37e-12 2.5e-09
HSA-MIR-222 -0.3416 2.267e-11 1.05e-08
HSA-MIR-133A-1 -0.3261 1.93e-10 8.95e-08
HSA-MIR-3676 -0.3108 1.967e-09 9.11e-07
HSA-MIR-217 0.2992 6.085e-09 2.81e-06
HSA-MIR-184 -0.3102 3.519e-08 1.62e-05
HSA-MIR-425 0.2818 4.74e-08 2.18e-05
Clinical variable #10: 'GLEASON_SCORE_SECONDARY'

6 miRs related to 'GLEASON_SCORE_SECONDARY'.

Table S18.  Basic characteristics of clinical feature: 'GLEASON_SCORE_SECONDARY'

GLEASON_SCORE_SECONDARY Mean (SD) 3.85 (0.64)
  Score N
  3 106
  4 205
  5 52
     
  Significant markers N = 6
  pos. correlated 3
  neg. correlated 3
List of 6 miRs differentially expressed by 'GLEASON_SCORE_SECONDARY'

Table S19.  Get Full Table List of 6 miRs significantly correlated to 'GLEASON_SCORE_SECONDARY' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-133B -0.2323 8.186e-06 0.00384
HSA-MIR-592 0.2462 1.089e-05 0.0051
HSA-MIR-217 0.2205 2.244e-05 0.0105
HSA-MIR-133A-2 -0.2225 2.337e-05 0.0109
HSA-MIR-514-3 -0.2364 0.0004179 0.194
HSA-MIR-21 0.1826 0.0004718 0.219
Clinical variable #11: 'GLEASON_SCORE'

43 miRs related to 'GLEASON_SCORE'.

Table S20.  Basic characteristics of clinical feature: 'GLEASON_SCORE'

GLEASON_SCORE Mean (SD) 7.51 (0.95)
  Score N
  6 31
  7 199
  8 51
  9 80
  10 2
     
  Significant markers N = 43
  pos. correlated 17
  neg. correlated 26
List of top 10 miRs differentially expressed by 'GLEASON_SCORE'

Table S21.  Get Full Table List of top 10 miRs significantly correlated to 'GLEASON_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-133B -0.3757 1.513e-13 7.09e-11
HSA-MIR-133A-2 -0.3622 1.924e-12 9.01e-10
HSA-MIR-217 0.3536 3.94e-12 1.84e-09
HSA-MIR-1-2 -0.352 5.014e-12 2.34e-09
HSA-MIR-221 -0.3462 1.17e-11 5.44e-09
HSA-MIR-222 -0.3274 1.629e-10 7.56e-08
HSA-MIR-592 0.333 1.621e-09 7.51e-07
HSA-MIR-133A-1 -0.3049 3.006e-09 1.39e-06
HSA-MIR-3676 -0.3032 5.009e-09 2.31e-06
HSA-MIR-21 0.2888 2.096e-08 9.64e-06
Clinical variable #12: 'PSA_RESULT_PREOP'

17 miRs related to 'PSA_RESULT_PREOP'.

Table S22.  Basic characteristics of clinical feature: 'PSA_RESULT_PREOP'

PSA_RESULT_PREOP Mean (SD) 10.6 (11)
  Significant markers N = 17
  pos. correlated 1
  neg. correlated 16
List of top 10 miRs differentially expressed by 'PSA_RESULT_PREOP'

Table S23.  Get Full Table List of top 10 miRs significantly correlated to 'PSA_RESULT_PREOP' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-145 -0.2449 2.484e-06 0.00117
HSA-MIR-222 -0.241 3.639e-06 0.0017
HSA-MIR-221 -0.2348 6.54e-06 0.00305
HSA-MIR-133A-1 -0.2208 2.302e-05 0.0107
HSA-MIR-15B 0.2159 3.53e-05 0.0164
HSA-MIR-100 -0.2124 4.748e-05 0.022
HSA-MIR-204 -0.2075 7.105e-05 0.0329
HSA-MIR-3647 -0.2035 0.0001012 0.0468
HSA-MIR-130A -0.201 0.0001201 0.0554
HSA-MIR-1-2 -0.198 0.0001525 0.0702
Clinical variable #13: 'PSA_VALUE'

No miR related to 'PSA_VALUE'.

Table S24.  Basic characteristics of clinical feature: 'PSA_VALUE'

PSA_VALUE Mean (SD) 0.98 (3.5)
  Significant markers N = 0
Clinical variable #14: 'RACE'

No miR related to 'RACE'.

Table S25.  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 = 363

  • Number of miRs = 469

  • Number of clinical features = 14

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

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] 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] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[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)