Correlation between miRseq expression and clinical features
Colorectal Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1ZW1JN7
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/C1ZW1JN7
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 420 miRs and 13 clinical features across 549 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one miRs.

  • 24 miRs correlated to 'AGE'.

    • HSA-MIR-432 ,  HSA-MIR-141 ,  HSA-MIR-153-2 ,  HSA-MIR-26A-1 ,  HSA-MIR-410 ,  ...

  • 57 miRs correlated to 'PRIMARY.SITE.OF.DISEASE'.

    • HSA-MIR-10B ,  HSA-MIR-1201 ,  HSA-MIR-30C-2 ,  HSA-MIR-425 ,  HSA-MIR-1259 ,  ...

  • 15 miRs correlated to 'NEOPLASM.DISEASESTAGE'.

    • HSA-MIR-625 ,  HSA-MIR-675 ,  HSA-MIR-143 ,  HSA-MIR-106A ,  HSA-MIR-616 ,  ...

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

    • HSA-MIR-501 ,  HSA-MIR-206 ,  HSA-MIR-500 ,  HSA-MIR-144 ,  HSA-MIR-191 ,  ...

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

    • HSA-MIR-146A ,  HSA-MIR-625 ,  HSA-MIR-1-2 ,  HSA-MIR-589 ,  HSA-MIR-217 ,  ...

  • 52 miRs correlated to 'PATHOLOGY.M.STAGE'.

    • HSA-LET-7F-2 ,  HSA-MIR-616 ,  HSA-MIR-628 ,  HSA-MIR-140 ,  HSA-MIR-106A ,  ...

  • 1 miR correlated to 'GENDER'.

    • HSA-MIR-651

  • 62 miRs correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-10B ,  HSA-MIR-1201 ,  HSA-MIR-30C-2 ,  HSA-MIR-20A ,  HSA-MIR-92A-1 ,  ...

  • 72 miRs correlated to 'COMPLETENESS.OF.RESECTION'.

    • HSA-MIR-330 ,  HSA-MIR-199B ,  HSA-MIR-136 ,  HSA-MIR-126 ,  HSA-MIR-1180 ,  ...

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

    • HSA-MIR-146A ,  HSA-MIR-511-1 ,  HSA-MIR-625 ,  HSA-MIR-223 ,  HSA-MIR-146B ,  ...

  • 3 miRs correlated to 'RACE'.

    • HSA-MIR-1304 ,  HSA-MIR-412 ,  HSA-MIR-15A

  • No miRs correlated to 'Time to Death', and 'RADIATIONS.RADIATION.REGIMENINDICATION'.

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=24 older N=9 younger N=15
PRIMARY SITE OF DISEASE Wilcoxon test N=57 rectum N=57 colon N=0
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=15        
PATHOLOGY T STAGE Spearman correlation test N=16 higher stage N=1 lower stage N=15
PATHOLOGY N STAGE Spearman correlation test N=6 higher stage N=2 lower stage N=4
PATHOLOGY M STAGE Kruskal-Wallis test N=52        
GENDER Wilcoxon test N=1 male N=1 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test N=62        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=72        
NUMBER OF LYMPH NODES Spearman correlation test N=6 higher number.of.lymph.nodes N=0 lower number.of.lymph.nodes N=6
RACE Kruskal-Wallis test N=3        
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) 0.1-140.4 (median=19.1)
  censored N = 419
  death N = 101
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

24 miRs related to 'AGE'.

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

AGE Mean (SD) 66.84 (13)
  Significant markers N = 24
  pos. correlated 9
  neg. correlated 15
List of top 10 miRs differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
HSA-MIR-432 -0.2232 1.517e-07 6.37e-05
HSA-MIR-141 0.1995 2.524e-06 0.00106
HSA-MIR-153-2 0.198 2.983e-06 0.00125
HSA-MIR-26A-1 0.1898 7.702e-06 0.00321
HSA-MIR-410 -0.1779 3.115e-05 0.013
HSA-MIR-411 -0.1699 7.051e-05 0.0293
HSA-MIR-493 -0.1629 0.0001279 0.053
HSA-MIR-431 -0.1618 0.0001423 0.0588
HSA-MIR-653 0.1635 0.0001435 0.0591
HSA-MIR-616 0.1614 0.0001637 0.0673
Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

57 miRs related to 'PRIMARY.SITE.OF.DISEASE'.

Table S4.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  COLON 405
  RECTUM 140
     
  Significant markers N = 57
  Higher in RECTUM 57
  Higher in COLON 0
List of top 10 miRs differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S5.  Get Full Table List of top 10 miRs differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

W(pos if higher in 'RECTUM') wilcoxontestP Q AUC
HSA-MIR-10B 14346 2.82e-18 1.18e-15 0.747
HSA-MIR-1201 41462 3.265e-16 1.37e-13 0.7313
HSA-MIR-30C-2 40396 6.41e-14 2.68e-11 0.7125
HSA-MIR-425 39037 2.866e-11 1.19e-08 0.6885
HSA-MIR-1259 38954 4.066e-11 1.69e-08 0.687
HSA-MIR-191 38281 6.304e-10 2.62e-07 0.6751
HSA-MIR-1977 37985 1.993e-09 8.25e-07 0.6699
HSA-MIR-20A 37931 2.45e-09 1.01e-06 0.669
HSA-LET-7G 37832 3.567e-09 1.47e-06 0.6672
HSA-MIR-1274B 18254 1.362e-08 5.6e-06 0.6627
Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

15 miRs related to 'NEOPLASM.DISEASESTAGE'.

Table S6.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 94
  STAGE IA 1
  STAGE II 36
  STAGE IIA 153
  STAGE IIB 10
  STAGE IIC 2
  STAGE III 27
  STAGE IIIA 17
  STAGE IIIB 69
  STAGE IIIC 45
  STAGE IV 57
  STAGE IVA 23
  STAGE IVB 1
     
  Significant markers N = 15
List of top 10 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S7.  Get Full Table List of top 10 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
HSA-MIR-625 6.248e-07 0.000262
HSA-MIR-675 4.001e-05 0.0168
HSA-MIR-143 4.667e-05 0.0195
HSA-MIR-106A 7.152e-05 0.0298
HSA-MIR-616 7.715e-05 0.0321
HSA-LET-7E 7.782e-05 0.0323
HSA-LET-7F-2 0.0001671 0.0692
HSA-MIR-141 0.0002114 0.0873
HSA-MIR-511-2 0.0003511 0.145
HSA-MIR-589 0.0003658 0.15
Clinical variable #5: 'PATHOLOGY.T.STAGE'

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

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.85 (0.64)
  N
  0 1
  1 19
  2 95
  3 376
  4 56
     
  Significant markers N = 16
  pos. correlated 1
  neg. correlated 15
List of top 10 miRs differentially expressed by 'PATHOLOGY.T.STAGE'

Table S9.  Get Full Table List of top 10 miRs significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-501 -0.1832 1.63e-05 0.00685
HSA-MIR-206 -0.229 2.911e-05 0.0122
HSA-MIR-500 -0.1755 3.681e-05 0.0154
HSA-MIR-144 -0.1696 6.735e-05 0.0281
HSA-MIR-191 -0.1656 9.987e-05 0.0415
HSA-MIR-502 -0.1638 0.0001184 0.0491
HSA-MIR-362 -0.1635 0.000123 0.0509
HSA-MIR-34C 0.1621 0.0001942 0.0802
HSA-MIR-2110 -0.1564 0.0002974 0.123
HSA-MIR-192 -0.1505 0.0004116 0.169
Clinical variable #6: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.61 (0.78)
  N
  0 313
  1 133
  2 99
     
  Significant markers N = 6
  pos. correlated 2
  neg. correlated 4
List of 6 miRs differentially expressed by 'PATHOLOGY.N.STAGE'

Table S11.  Get Full Table List of 6 miRs significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-146A -0.1784 2.8e-05 0.0118
HSA-MIR-625 -0.1772 3.176e-05 0.0133
HSA-MIR-1-2 0.1579 0.0002141 0.0895
HSA-MIR-589 -0.1536 0.0003181 0.133
HSA-MIR-217 0.1492 0.0004748 0.198
HSA-MIR-511-1 -0.1482 0.0005517 0.229
Clinical variable #7: 'PATHOLOGY.M.STAGE'

52 miRs related to 'PATHOLOGY.M.STAGE'.

Table S12.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 412
  M1 68
  M1A 9
  M1B 1
  MX 50
     
  Significant markers N = 52
List of top 10 miRs differentially expressed by 'PATHOLOGY.M.STAGE'

Table S13.  Get Full Table List of top 10 miRs differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
HSA-LET-7F-2 2.47e-08 1.04e-05
HSA-MIR-616 6.166e-08 2.58e-05
HSA-MIR-628 9.078e-08 3.79e-05
HSA-MIR-140 1.232e-07 5.14e-05
HSA-MIR-106A 3.111e-07 0.000129
HSA-MIR-301A 4.081e-07 0.000169
HSA-MIR-142 5.059e-07 0.000209
HSA-LET-7A-1 8.811e-07 0.000364
HSA-LET-7A-2 1.029e-06 0.000424
HSA-LET-7A-3 1.099e-06 0.000452
Clinical variable #8: 'GENDER'

One miR related to 'GENDER'.

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

GENDER Labels N
  FEMALE 257
  MALE 292
     
  Significant markers N = 1
  Higher in MALE 1
  Higher in FEMALE 0
List of one miR differentially expressed by 'GENDER'

Table S15.  Get Full Table List of one miR differentially expressed by 'GENDER'. 0 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HSA-MIR-651 29094 6.504e-05 0.0273 0.5995
Clinical variable #9: 'HISTOLOGICAL.TYPE'

62 miRs related to 'HISTOLOGICAL.TYPE'.

Table S16.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 351
  COLON MUCINOUS ADENOCARCINOMA 53
  RECTAL ADENOCARCINOMA 127
  RECTAL MUCINOUS ADENOCARCINOMA 10
     
  Significant markers N = 62
List of top 10 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

Table S17.  Get Full Table List of top 10 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
HSA-MIR-10B 1.206e-16 5.07e-14
HSA-MIR-1201 1.429e-14 5.99e-12
HSA-MIR-30C-2 2.229e-12 9.32e-10
HSA-MIR-20A 4.123e-11 1.72e-08
HSA-MIR-92A-1 4.572e-11 1.9e-08
HSA-MIR-425 1.099e-10 4.56e-08
HSA-MIR-1259 2.36e-10 9.77e-08
HSA-LET-7G 3.997e-10 1.65e-07
HSA-MIR-592 6.325e-10 2.61e-07
HSA-MIR-31 3.56e-09 1.46e-06
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No miR related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S18.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 9
  YES 540
     
  Significant markers N = 0
Clinical variable #11: 'COMPLETENESS.OF.RESECTION'

72 miRs related to 'COMPLETENESS.OF.RESECTION'.

Table S19.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 384
  R1 5
  R2 36
  RX 26
     
  Significant markers N = 72
List of top 10 miRs differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S20.  Get Full Table List of top 10 miRs differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
HSA-MIR-330 1.756e-08 7.37e-06
HSA-MIR-199B 4.404e-08 1.85e-05
HSA-MIR-136 5.042e-08 2.11e-05
HSA-MIR-126 6.41e-08 2.67e-05
HSA-MIR-1180 6.661e-08 2.77e-05
HSA-LET-7A-1 8.048e-08 3.34e-05
HSA-MIR-590 8.652e-08 3.58e-05
HSA-LET-7A-2 8.886e-08 3.67e-05
HSA-LET-7A-3 1.002e-07 4.13e-05
HSA-MIR-16-1 1.211e-07 4.98e-05
Clinical variable #12: 'NUMBER.OF.LYMPH.NODES'

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

Table S21.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.19 (4.7)
  Significant markers N = 6
  pos. correlated 0
  neg. correlated 6
List of 6 miRs differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S22.  Get Full Table List of 6 miRs significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-146A -0.176 6.001e-05 0.0252
HSA-MIR-511-1 -0.1739 7.993e-05 0.0335
HSA-MIR-625 -0.1653 0.0001674 0.07
HSA-MIR-223 -0.161 0.0002469 0.103
HSA-MIR-146B -0.1517 0.0005565 0.232
HSA-MIR-128-2 -0.1487 0.0007179 0.298
Clinical variable #13: 'RACE'

3 miRs related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 12
  BLACK OR AFRICAN AMERICAN 26
  WHITE 280
     
  Significant markers N = 3
List of 3 miRs differentially expressed by 'RACE'

Table S24.  Get Full Table List of 3 miRs differentially expressed by 'RACE'

ANOVA_P Q
HSA-MIR-1304 4.082e-06 0.00171
HSA-MIR-412 4.502e-05 0.0189
HSA-MIR-15A 9.473e-05 0.0396
Methods & Data
Input

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

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

  • Number of patients = 549

  • Number of miRs = 420

  • Number of clinical features = 13

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)
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