Correlation between miRseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1FF3RQ7
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1FF3RQ7
Overview
Introduction

This pipeline uses various statistical tests to identify miRs whose log2 expression levels correlated to selected clinical features. The input file " COAD-TP.miRseq_RPKM_log2.txt " is generated in the pipeline miRseq_Preprocess in the stddata run.

Summary

Testing the association between 416 miRs and 12 clinical features across 406 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one miRs.

  • 30 miRs correlated to 'YEARS_TO_BIRTH'.

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

  • 30 miRs correlated to 'PATHOLOGIC_STAGE'.

    • HSA-MIR-625 ,  HSA-MIR-616 ,  HSA-MIR-1-2 ,  HSA-MIR-133A-1 ,  HSA-MIR-106A ,  ...

  • 24 miRs correlated to 'PATHOLOGY_T_STAGE'.

    • HSA-MIR-501 ,  HSA-MIR-206 ,  HSA-MIR-362 ,  HSA-MIR-192 ,  HSA-MIR-147B ,  ...

  • 28 miRs correlated to 'PATHOLOGY_N_STAGE'.

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

  • 30 miRs correlated to 'PATHOLOGY_M_STAGE'.

    • HSA-MIR-625 ,  HSA-MIR-589 ,  HSA-MIR-1180 ,  HSA-MIR-1307 ,  HSA-MIR-629 ,  ...

  • 5 miRs correlated to 'GENDER'.

    • HSA-MIR-651 ,  HSA-MIR-320C-2 ,  HSA-MIR-1468 ,  HSA-MIR-99B ,  HSA-MIR-219-2

  • 30 miRs correlated to 'HISTOLOGICAL_TYPE'.

    • HSA-MIR-592 ,  HSA-MIR-31 ,  HSA-MIR-552 ,  HSA-MIR-92A-1 ,  HSA-MIR-196B ,  ...

  • 30 miRs correlated to 'RESIDUAL_TUMOR'.

    • HSA-LET-7F-2 ,  HSA-MIR-1180 ,  HSA-LET-7A-1 ,  HSA-LET-7A-2 ,  HSA-LET-7A-3 ,  ...

  • 23 miRs correlated to 'NUMBER_OF_LYMPH_NODES'.

    • HSA-MIR-625 ,  HSA-MIR-223 ,  HSA-MIR-146A ,  HSA-MIR-21 ,  HSA-MIR-1-2 ,  ...

  • 5 miRs correlated to 'RACE'.

    • HSA-MIR-1304 ,  HSA-MIR-412 ,  HSA-MIR-15A ,  HSA-MIR-27A ,  HSA-MIR-376A-1

  • No miRs correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', and 'RADIATION_THERAPY'.

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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=18 younger N=12
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=24 higher stage N=6 lower stage N=18
PATHOLOGY_N_STAGE Spearman correlation test N=28 higher stage N=9 lower stage N=19
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=5 male N=5 female N=0
RADIATION_THERAPY Wilcoxon test   N=0        
HISTOLOGICAL_TYPE Wilcoxon test N=30 colon mucinous adenocarcinoma N=30 colon adenocarcinoma N=0
RESIDUAL_TUMOR Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=23 higher number_of_lymph_nodes N=4 lower number_of_lymph_nodes N=19
RACE Kruskal-Wallis test N=5        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No miR related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

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

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0-148 (median=23.5)
  censored N = 315
  death N = 90
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 miRs related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 67.35 (13)
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
List of top 10 miRs differentially expressed by 'YEARS_TO_BIRTH'

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

SpearmanCorr corrP Q
HSA-MIR-26A-1 0.2329 2.149e-06 0.00045
HSA-MIR-432 -0.2346 2.161e-06 0.00045
HSA-MIR-153-2 0.2261 4.321e-06 0.000464
HSA-MIR-141 0.2258 4.463e-06 0.000464
HSA-MIR-410 -0.2052 3.401e-05 0.00283
HSA-MIR-653 0.2011 5.674e-05 0.0034
HSA-MIR-34A 0.1982 5.918e-05 0.0034
HSA-MIR-616 0.1969 7.655e-05 0.0034
HSA-MIR-577 0.1948 7.933e-05 0.0034
HSA-MIR-142 0.1945 8.164e-05 0.0034
Clinical variable #3: 'PATHOLOGIC_STAGE'

30 miRs related to 'PATHOLOGIC_STAGE'.

Table S4.  Basic characteristics of clinical feature: 'PATHOLOGIC_STAGE'

PATHOLOGIC_STAGE Labels N
  STAGE I 66
  STAGE IA 1
  STAGE II 29
  STAGE IIA 120
  STAGE IIB 8
  STAGE IIC 1
  STAGE III 20
  STAGE IIIA 7
  STAGE IIIB 52
  STAGE IIIC 34
  STAGE IV 42
  STAGE IVA 15
  STAGE IVB 1
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'PATHOLOGIC_STAGE'

Table S5.  Get Full Table List of top 10 miRs differentially expressed by 'PATHOLOGIC_STAGE'

kruskal_wallis_P Q
HSA-MIR-625 5.8e-05 0.0241
HSA-MIR-616 0.000233 0.0485
HSA-MIR-1-2 0.0007731 0.0827
HSA-MIR-133A-1 0.0009144 0.0827
HSA-MIR-106A 0.00108 0.0827
HSA-MIR-155 0.001622 0.0827
HSA-MIR-141 0.001653 0.0827
HSA-MIR-143 0.00191 0.0827
HSA-MIR-675 0.002077 0.0827
HSA-MIR-146A 0.002098 0.0827
Clinical variable #4: 'PATHOLOGY_T_STAGE'

24 miRs related to 'PATHOLOGY_T_STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 2.89 (0.62)
  N
  T1 11
  T2 68
  T3 280
  T4 46
     
  Significant markers N = 24
  pos. correlated 6
  neg. correlated 18
List of top 10 miRs differentially expressed by 'PATHOLOGY_T_STAGE'

Table S7.  Get Full Table List of top 10 miRs significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-501 -0.1918 0.0001025 0.0426
HSA-MIR-206 -0.2351 0.0003865 0.0804
HSA-MIR-362 -0.167 0.0007418 0.0907
HSA-MIR-192 -0.1587 0.001357 0.0907
HSA-MIR-147B -0.1586 0.001441 0.0907
HSA-MIR-500 -0.1574 0.00148 0.0907
HSA-MIR-502 -0.157 0.001525 0.0907
HSA-MIR-191 -0.1499 0.002494 0.13
HSA-LET-7E 0.1421 0.004173 0.193
HSA-MIR-224 -0.1339 0.006981 0.285
Clinical variable #5: 'PATHOLOGY_N_STAGE'

28 miRs related to 'PATHOLOGY_N_STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 0.59 (0.77)
  N
  N0 238
  N1 96
  N2 72
     
  Significant markers N = 28
  pos. correlated 9
  neg. correlated 19
List of top 10 miRs differentially expressed by 'PATHOLOGY_N_STAGE'

Table S9.  Get Full Table List of top 10 miRs significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-625 -0.1691 0.0006224 0.238
HSA-MIR-1-2 0.1566 0.001545 0.238
HSA-MIR-146A -0.1485 0.002696 0.238
HSA-MIR-217 0.1435 0.003758 0.238
HSA-MIR-589 -0.1431 0.003865 0.238
HSA-MIR-216A 0.1533 0.005409 0.238
HSA-MIR-146B -0.1377 0.005434 0.238
HSA-MIR-133A-1 0.1376 0.005489 0.238
HSA-MIR-942 -0.1367 0.005805 0.238
HSA-MIR-30A 0.1339 0.00691 0.238
Clinical variable #6: 'PATHOLOGY_M_STAGE'

30 miRs related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 307
  class1 58
     
  Significant markers N = 30
  Higher in class1 30
  Higher in class0 0
List of top 10 miRs differentially expressed by 'PATHOLOGY_M_STAGE'

Table S11.  Get Full Table List of top 10 miRs differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
HSA-MIR-625 5974 7.072e-05 0.0294 0.6645
HSA-MIR-589 6226 0.0002813 0.0585 0.6503
HSA-MIR-1180 6300 0.0005135 0.0712 0.6439
HSA-MIR-1307 6494 0.001082 0.0954 0.6353
HSA-MIR-629 6506 0.001146 0.0954 0.6346
HSA-MIR-1249 5636 0.001405 0.0974 0.6354
HSA-MIR-886 6599 0.001773 0.105 0.6294
HSA-MIR-146A 6673 0.002484 0.129 0.6252
HSA-MIR-1976 6728 0.00317 0.146 0.6221
HSA-MIR-501 6768 0.003774 0.146 0.6199
Clinical variable #7: 'GENDER'

5 miRs related to 'GENDER'.

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

GENDER Labels N
  FEMALE 191
  MALE 215
     
  Significant markers N = 5
  Higher in MALE 5
  Higher in FEMALE 0
List of 5 miRs differentially expressed by 'GENDER'

Table S13.  Get Full Table List of 5 miRs 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 15927 0.0008504 0.193 0.5968
HSA-MIR-320C-2 3666 0.0009287 0.193 0.6355
HSA-MIR-1468 23319 0.002353 0.277 0.5882
HSA-MIR-99B 17060 0.003261 0.277 0.5846
HSA-MIR-219-2 5759 0.003327 0.277 0.6093
Clinical variable #8: 'RADIATION_THERAPY'

No miR related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 333
  YES 8
     
  Significant markers N = 0
Clinical variable #9: 'HISTOLOGICAL_TYPE'

30 miRs related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  COLON ADENOCARCINOMA 347
  COLON MUCINOUS ADENOCARCINOMA 54
     
  Significant markers N = 30
  Higher in COLON MUCINOUS ADENOCARCINOMA 30
  Higher in COLON ADENOCARCINOMA 0
List of top 10 miRs differentially expressed by 'HISTOLOGICAL_TYPE'

Table S16.  Get Full Table List of top 10 miRs differentially expressed by 'HISTOLOGICAL_TYPE'

W(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA') wilcoxontestP Q AUC
HSA-MIR-592 4722 1.291e-08 5.37e-06 0.7425
HSA-MIR-31 13145 1.18e-07 2.45e-05 0.7245
HSA-MIR-552 5488 9.69e-07 0.000134 0.7071
HSA-MIR-92A-1 5623 2.274e-06 0.000236 0.6999
HSA-MIR-196B 5757 5.157e-06 0.00038 0.6928
HSA-MIR-574 12971 5.476e-06 0.00038 0.6922
HSA-MIR-92A-2 5836 8.25e-06 0.00049 0.6885
HSA-MIR-335 5966 1.751e-05 0.000818 0.6816
HSA-MIR-29A 5968 1.771e-05 0.000818 0.6815
HSA-MIR-1247 6007 2.208e-05 0.000918 0.6794
Clinical variable #10: 'RESIDUAL_TUMOR'

30 miRs related to 'RESIDUAL_TUMOR'.

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

RESIDUAL_TUMOR Labels N
  R0 284
  R1 4
  R2 25
  RX 22
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'RESIDUAL_TUMOR'

Table S18.  Get Full Table List of top 10 miRs differentially expressed by 'RESIDUAL_TUMOR'

kruskal_wallis_P Q
HSA-LET-7F-2 3.91e-07 4.1e-05
HSA-MIR-1180 4.399e-07 4.1e-05
HSA-LET-7A-1 4.665e-07 4.1e-05
HSA-LET-7A-2 4.864e-07 4.1e-05
HSA-LET-7A-3 5.629e-07 4.1e-05
HSA-MIR-126 5.907e-07 4.1e-05
HSA-MIR-199B 7.316e-07 4.22e-05
HSA-MIR-136 8.158e-07 4.22e-05
HSA-MIR-16-1 9.135e-07 4.22e-05
HSA-MIR-497 1.472e-06 6.12e-05
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

23 miRs related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 2.05 (4.5)
  Significant markers N = 23
  pos. correlated 4
  neg. correlated 19
List of top 10 miRs differentially expressed by 'NUMBER_OF_LYMPH_NODES'

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

SpearmanCorr corrP Q
HSA-MIR-625 -0.1665 0.001071 0.258
HSA-MIR-223 -0.1594 0.001757 0.258
HSA-MIR-146A -0.1538 0.002547 0.258
HSA-MIR-21 -0.1487 0.003543 0.258
HSA-MIR-1-2 0.1463 0.004102 0.258
HSA-MIR-146B -0.1441 0.004727 0.258
HSA-MIR-511-1 -0.1429 0.005304 0.258
HSA-MIR-1262 -0.1477 0.005497 0.258
HSA-MIR-942 -0.1392 0.006348 0.258
HSA-MIR-766 -0.1381 0.006782 0.258
Clinical variable #12: 'RACE'

5 miRs related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 11
  BLACK OR AFRICAN AMERICAN 23
  WHITE 213
     
  Significant markers N = 5
List of 5 miRs differentially expressed by 'RACE'

Table S22.  Get Full Table List of 5 miRs differentially expressed by 'RACE'

kruskal_wallis_P Q
HSA-MIR-1304 1.338e-05 0.00557
HSA-MIR-412 0.0004194 0.0872
HSA-MIR-15A 0.0007698 0.107
HSA-MIR-27A 0.001725 0.159
HSA-MIR-376A-1 0.001909 0.159
Methods & Data
Input

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

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

  • Number of patients = 406

  • Number of miRs = 416

  • Number of clinical features = 12

Selected clinical features

  • Further details on clinical features selected for this analysis, please find a documentation on selected CDEs (Clinical Data Elements). The first column of the file is a formula to convert values and the second column is a clinical parameter name.

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

Survival analysis

For survival clinical features, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[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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