Correlation between miRseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C18K7828
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C18K7828
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 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 'NEOPLASM_DISEASESTAGE'.

    • HSA-MIR-625 ,  HSA-MIR-616 ,  HSA-MIR-143 ,  HSA-MIR-1-2 ,  HSA-MIR-141 ,  ...

  • 30 miRs correlated to 'PATHOLOGY_T_STAGE'.

    • HSA-MIR-501 ,  HSA-MIR-362 ,  HSA-MIR-206 ,  HSA-MIR-502 ,  HSA-MIR-500 ,  ...

  • 30 miRs correlated to 'PATHOLOGY_N_STAGE'.

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

  • 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-574 ,  HSA-MIR-552 ,  HSA-MIR-92A-1 ,  ...

  • 30 miRs correlated to 'COMPLETENESS_OF_RESECTION'.

    • HSA-LET-7F-2 ,  HSA-LET-7A-1 ,  HSA-LET-7A-2 ,  HSA-LET-7A-3 ,  HSA-MIR-126 ,  ...

  • 20 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 '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
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
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=5 lower stage N=25
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=9 lower stage N=21
PATHOLOGY_M_STAGE Wilcoxon test N=30 class1 N=30 class0 N=0
GENDER Wilcoxon test N=5 male N=5 female N=0
HISTOLOGICAL_TYPE Wilcoxon test N=30 colon mucinous adenocarcinoma N=30 colon adenocarcinoma N=0
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS_OF_RESECTION Kruskal-Wallis test N=30        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=20 higher number_of_lymph_nodes N=4 lower number_of_lymph_nodes N=16
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) 0-140.4 (median=21.8)
  censored N = 320
  death N = 85
     
  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: 'NEOPLASM_DISEASESTAGE'

30 miRs related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 66
  STAGE IA 1
  STAGE II 28
  STAGE IIA 121
  STAGE IIB 8
  STAGE IIC 1
  STAGE III 21
  STAGE IIIA 11
  STAGE IIIB 49
  STAGE IIIC 32
  STAGE IV 42
  STAGE IVA 16
  STAGE IVB 1
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'NEOPLASM_DISEASESTAGE'

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

kruskal_wallis_P Q
HSA-MIR-625 3.309e-05 0.0138
HSA-MIR-616 0.0002114 0.044
HSA-MIR-143 0.000961 0.0933
HSA-MIR-1-2 0.001116 0.0933
HSA-MIR-141 0.001121 0.0933
HSA-MIR-106A 0.001469 0.102
HSA-MIR-133A-1 0.002412 0.116
HSA-MIR-577 0.002501 0.116
HSA-MIR-675 0.002502 0.116
HSA-MIR-589 0.002981 0.118
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 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 69
  T3 279
  T4 46
     
  Significant markers N = 30
  pos. correlated 5
  neg. correlated 25
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 -0.1976 6.249e-05 0.026
HSA-MIR-362 -0.1738 0.0004429 0.0784
HSA-MIR-206 -0.2269 0.0006216 0.0784
HSA-MIR-502 -0.1641 0.0009139 0.0784
HSA-MIR-500 -0.1637 0.0009419 0.0784
HSA-MIR-192 -0.1602 0.001217 0.0787
HSA-MIR-147B -0.1598 0.001324 0.0787
HSA-MIR-191 -0.1514 0.002248 0.117
HSA-LET-7E 0.1411 0.004429 0.188
HSA-MIR-224 -0.1408 0.004515 0.188
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 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 95
  N2 72
     
  Significant markers N = 30
  pos. correlated 9
  neg. correlated 21
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 -0.1694 0.0006208 0.219
HSA-MIR-1-2 0.1571 0.001517 0.219
HSA-MIR-146A -0.1512 0.002284 0.219
HSA-MIR-589 -0.1471 0.003011 0.219
HSA-MIR-217 0.1437 0.003748 0.219
HSA-MIR-216A 0.1575 0.0043 0.219
HSA-MIR-942 -0.1405 0.004626 0.219
HSA-MIR-146B -0.1374 0.005603 0.219
HSA-MIR-133A-1 0.1366 0.005882 0.219
HSA-MIR-618 -0.1762 0.006535 0.219
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 305
  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 5961 8.272e-05 0.0344 0.663
HSA-MIR-589 6149 0.0002335 0.0486 0.6524
HSA-MIR-1180 6289 0.0006034 0.0837 0.6421
HSA-MIR-1307 6456 0.001112 0.0994 0.635
HSA-MIR-629 6471 0.001195 0.0994 0.6342
HSA-MIR-1249 5601 0.00146 0.101 0.635
HSA-MIR-146A 6586 0.002048 0.109 0.6277
HSA-MIR-886 6592 0.002105 0.109 0.6274
HSA-MIR-1976 6695 0.003342 0.131 0.6215
HSA-MIR-501 6697 0.003372 0.131 0.6214
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: 'HISTOLOGICAL_TYPE'

30 miRs related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  COLON ADENOCARCINOMA 351
  COLON MUCINOUS ADENOCARCINOMA 53
     
  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 S15.  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 4710 1.97e-08 8.2e-06 0.7412
HSA-MIR-31 13176 6.114e-08 1.27e-05 0.7312
HSA-MIR-574 13099 1.652e-06 0.000229 0.7041
HSA-MIR-552 5555 2.272e-06 0.000236 0.7014
HSA-MIR-92A-1 5635 3.717e-06 0.000309 0.6971
HSA-MIR-196B 5796 9.714e-06 0.000674 0.6884
HSA-MIR-1247 5823 1.137e-05 0.000676 0.687
HSA-MIR-29A 5895 1.72e-05 0.000894 0.6831
HSA-MIR-92A-2 5951 2.36e-05 0.00109 0.6801
HSA-MIR-98 6179 8.146e-05 0.00339 0.6678
Clinical variable #9: 'RADIATIONS_RADIATION_REGIMENINDICATION'

No miR related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 3
  YES 403
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS_OF_RESECTION'

30 miRs related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 282
  R1 3
  R2 25
  RX 22
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'COMPLETENESS_OF_RESECTION'

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

kruskal_wallis_P Q
HSA-LET-7F-2 3.704e-07 4.4e-05
HSA-LET-7A-1 4.394e-07 4.4e-05
HSA-LET-7A-2 4.592e-07 4.4e-05
HSA-LET-7A-3 5.326e-07 4.4e-05
HSA-MIR-126 5.683e-07 4.4e-05
HSA-MIR-199B 7.502e-07 4.4e-05
HSA-MIR-16-1 8.694e-07 4.4e-05
HSA-MIR-1180 8.74e-07 4.4e-05
HSA-MIR-136 9.51e-07 4.4e-05
HSA-MIR-497 1.497e-06 6.23e-05
Clinical variable #11: 'NUMBER_OF_LYMPH_NODES'

20 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 = 20
  pos. correlated 4
  neg. correlated 16
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 -0.1659 0.001136 0.213
HSA-MIR-223 -0.158 0.001956 0.213
HSA-MIR-146A -0.153 0.002719 0.213
HSA-MIR-21 -0.1487 0.003573 0.213
HSA-MIR-1-2 0.1475 0.003856 0.213
HSA-MIR-146B -0.1422 0.00536 0.213
HSA-MIR-511-1 -0.1418 0.005749 0.213
HSA-MIR-1262 -0.1471 0.005755 0.213
HSA-MIR-942 -0.1407 0.005862 0.213
HSA-MIR-580 -0.1605 0.006056 0.213
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

  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • 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, 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

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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