Correlation between miRseq expression and clinical features
Stomach and Esophageal carcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1ZW1KC2
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/C1ZW1KC2
Overview
Introduction

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

Summary

Testing the association between 514 miRs and 12 clinical features across 620 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one miRs.

  • 2 miRs correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • HSA-MIR-548V ,  HSA-MIR-103-2

  • 30 miRs correlated to 'YEARS_TO_BIRTH'.

    • HSA-MIR-194-1 ,  HSA-MIR-194-2 ,  HSA-MIR-215 ,  HSA-MIR-192 ,  HSA-MIR-29B-1 ,  ...

  • 30 miRs correlated to 'PATHOLOGIC_STAGE'.

    • HSA-MIR-199B ,  HSA-MIR-199A-2 ,  HSA-MIR-199A-1 ,  HSA-MIR-654 ,  HSA-MIR-134 ,  ...

  • 30 miRs correlated to 'PATHOLOGY_T_STAGE'.

    • HSA-MIR-217 ,  HSA-MIR-132 ,  HSA-MIR-199A-1 ,  HSA-MIR-199A-2 ,  HSA-MIR-100 ,  ...

  • 30 miRs correlated to 'PATHOLOGY_N_STAGE'.

    • HSA-MIR-217 ,  HSA-MIR-203 ,  HSA-MIR-205 ,  HSA-MIR-944 ,  HSA-MIR-27A ,  ...

  • 5 miRs correlated to 'PATHOLOGY_M_STAGE'.

    • HSA-MIR-1274B ,  HSA-MIR-495 ,  HSA-MIR-654 ,  HSA-MIR-181A-2 ,  HSA-MIR-337

  • 30 miRs correlated to 'GENDER'.

    • HSA-MIR-216A ,  HSA-MIR-3176 ,  HSA-MIR-326 ,  HSA-MIR-132 ,  HSA-MIR-330 ,  ...

  • 30 miRs correlated to 'RADIATION_THERAPY'.

    • HSA-LET-7A-1 ,  HSA-LET-7A-3 ,  HSA-LET-7A-2 ,  HSA-LET-7F-2 ,  HSA-MIR-628 ,  ...

  • 30 miRs correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • HSA-MIR-4326 ,  HSA-MIR-107 ,  HSA-MIR-181C ,  HSA-MIR-26A-2 ,  HSA-MIR-3691 ,  ...

  • 30 miRs correlated to 'RACE'.

    • HSA-MIR-3130-1 ,  HSA-MIR-412 ,  HSA-MIR-4326 ,  HSA-MIR-9-3 ,  HSA-MIR-1304 ,  ...

  • 13 miRs correlated to 'ETHNICITY'.

    • HSA-MIR-144 ,  HSA-MIR-3679 ,  HSA-MIR-3917 ,  HSA-MIR-1304 ,  HSA-MIR-223 ,  ...

  • No miRs correlated to 'NUMBER_PACK_YEARS_SMOKED'

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=2   N=NA   N=NA
YEARS_TO_BIRTH Spearman correlation test N=30 older N=23 younger N=7
PATHOLOGIC_STAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=13 lower stage N=17
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=8 lower stage N=22
PATHOLOGY_M_STAGE Wilcoxon test N=5 class1 N=5 class0 N=0
GENDER Wilcoxon test N=30 male N=30 female N=0
RADIATION_THERAPY Wilcoxon test N=30 yes N=30 no N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=30 higher score N=18 lower score N=12
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test N=13 not hispanic or latino N=13 hispanic or latino N=0
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

2 miRs 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) 0-122.3 (median=13.9)
  censored N = 370
  death N = 249
     
  Significant markers N = 2
  associated with shorter survival NA
  associated with longer survival NA
List of 2 miRs differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of 2 miRs significantly associated with 'Time to Death' by Cox regression test. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

logrank_P Q C_index
HSA-MIR-548V 0.000432 0.22 0.53
HSA-MIR-103-2 0.000906 0.23 0.532
Clinical variable #2: 'YEARS_TO_BIRTH'

30 miRs related to 'YEARS_TO_BIRTH'.

Table S3.  Basic characteristics of clinical feature: 'YEARS_TO_BIRTH'

YEARS_TO_BIRTH Mean (SD) 64.77 (11)
  Significant markers N = 30
  pos. correlated 23
  neg. correlated 7
List of top 10 miRs differentially expressed by 'YEARS_TO_BIRTH'

Table S4.  Get Full Table List of top 10 miRs significantly correlated to 'YEARS_TO_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-194-1 0.252 2.627e-10 7.56e-08
HSA-MIR-194-2 0.2514 2.94e-10 7.56e-08
HSA-MIR-215 0.2432 1.129e-09 1.62e-07
HSA-MIR-192 0.2425 1.26e-09 1.62e-07
HSA-MIR-29B-1 0.2302 8.585e-09 8.83e-07
HSA-MIR-29B-2 0.2267 1.465e-08 1.25e-06
HSA-MIR-153-2 0.2177 5.572e-08 4.09e-06
HSA-MIR-375 0.2125 1.14e-07 7.32e-06
HSA-MIR-592 0.2078 4.034e-07 2.3e-05
HSA-MIR-326 0.2018 5.341e-07 2.62e-05
Clinical variable #3: 'PATHOLOGIC_STAGE'

30 miRs related to 'PATHOLOGIC_STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGIC_STAGE'

PATHOLOGIC_STAGE Labels N
  STAGE I 10
  STAGE IA 21
  STAGE IB 46
  STAGE II 33
  STAGE IIA 87
  STAGE IIB 86
  STAGE III 29
  STAGE IIIA 94
  STAGE IIIB 70
  STAGE IIIC 46
  STAGE IV 48
  STAGE IVA 4
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'PATHOLOGIC_STAGE'

Table S6.  Get Full Table List of top 10 miRs differentially expressed by 'PATHOLOGIC_STAGE'

kruskal_wallis_P Q
HSA-MIR-199B 4.493e-11 1.03e-08
HSA-MIR-199A-2 6.003e-11 1.03e-08
HSA-MIR-199A-1 6.019e-11 1.03e-08
HSA-MIR-654 1.965e-10 2.06e-08
HSA-MIR-134 2.005e-10 2.06e-08
HSA-MIR-127 4.252e-10 3.64e-08
HSA-MIR-152 2.537e-09 1.86e-07
HSA-MIR-337 3.749e-09 2.41e-07
HSA-MIR-708 4.484e-09 2.56e-07
HSA-MIR-100 5.992e-09 3.08e-07
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 miRs related to 'PATHOLOGY_T_STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 2.79 (0.88)
  N
  T0 1
  T1 54
  T2 135
  T3 280
  T4 123
     
  Significant markers N = 30
  pos. correlated 13
  neg. correlated 17
List of top 10 miRs differentially expressed by 'PATHOLOGY_T_STAGE'

Table S8.  Get Full Table List of top 10 miRs significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-217 0.2813 3.164e-12 1.63e-09
HSA-MIR-132 0.267 3.89e-11 1e-08
HSA-MIR-199A-1 0.2635 7.071e-11 1.21e-08
HSA-MIR-199A-2 0.2602 1.247e-10 1.6e-08
HSA-MIR-100 0.2516 5.131e-10 5.27e-08
HSA-MIR-199B 0.2476 9.904e-10 7.42e-08
HSA-MIR-205 -0.2755 1.011e-09 7.42e-08
HSA-MIR-490 0.2548 4.066e-08 2.61e-06
HSA-MIR-556 -0.2297 2.519e-07 1.44e-05
HSA-MIR-125B-1 0.2089 2.869e-07 1.47e-05
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 miRs related to 'PATHOLOGY_N_STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 1.14 (1.1)
  N
  N0 205
  N1 186
  N2 97
  N3 95
     
  Significant markers N = 30
  pos. correlated 8
  neg. correlated 22
List of top 10 miRs differentially expressed by 'PATHOLOGY_N_STAGE'

Table S10.  Get Full Table List of top 10 miRs significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-217 0.209 3.629e-07 0.000126
HSA-MIR-203 -0.2065 4.898e-07 0.000126
HSA-MIR-205 -0.2088 5.362e-06 0.000919
HSA-MIR-944 -0.2026 8.54e-06 0.0011
HSA-MIR-27A -0.172 2.983e-05 0.00307
HSA-MIR-193B -0.1698 3.77e-05 0.00323
HSA-MIR-149 -0.1617 8.767e-05 0.00613
HSA-MIR-365-2 -0.1603 0.0001015 0.00613
HSA-MIR-24-2 -0.1597 0.0001073 0.00613
HSA-MIR-1249 -0.1571 0.0002052 0.00966
Clinical variable #6: 'PATHOLOGY_M_STAGE'

5 miRs related to 'PATHOLOGY_M_STAGE'.

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGY_M_STAGE'

PATHOLOGY_M_STAGE Labels N
  class0 519
  class1 39
     
  Significant markers N = 5
  Higher in class1 5
  Higher in class0 0
List of 5 miRs differentially expressed by 'PATHOLOGY_M_STAGE'

Table S12.  Get Full Table List of 5 miRs differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
HSA-MIR-1274B 12584 0.0005125 0.263 0.669
HSA-MIR-495 13246 0.00129 0.27 0.6544
HSA-MIR-654 13123 0.001991 0.27 0.6483
HSA-MIR-181A-2 13094 0.002201 0.27 0.6469
HSA-MIR-337 13042 0.002628 0.27 0.6443
Clinical variable #7: 'GENDER'

30 miRs related to 'GENDER'.

Table S13.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 182
  MALE 438
     
  Significant markers N = 30
  Higher in MALE 30
  Higher in FEMALE 0
List of top 10 miRs differentially expressed by 'GENDER'

Table S14.  Get Full Table List of top 10 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-216A 19508 4.329e-05 0.00638 0.6161
HSA-MIR-3176 9702 4.753e-05 0.00638 0.6375
HSA-MIR-326 31130 5.413e-05 0.00638 0.6033
HSA-MIR-132 31721 6.176e-05 0.00638 0.6021
HSA-MIR-330 31792 7.156e-05 0.00638 0.6012
HSA-MIR-142 31811 7.443e-05 0.00638 0.6009
HSA-MIR-1274B 29465 0.0001603 0.0118 0.5982
HSA-MIR-766 32411 0.0002461 0.0158 0.5934
HSA-MIR-935 28004 0.0004127 0.0236 0.5933
HSA-MIR-103-1 46704 0.0007507 0.0386 0.5859
Clinical variable #8: 'RADIATION_THERAPY'

30 miRs related to 'RADIATION_THERAPY'.

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

RADIATION_THERAPY Labels N
  NO 443
  YES 116
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 miRs differentially expressed by 'RADIATION_THERAPY'

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

W(pos if higher in 'YES') wilcoxontestP Q AUC
HSA-LET-7A-1 31185 0.0003919 0.0742 0.6069
HSA-LET-7A-3 31181 0.0003957 0.0742 0.6068
HSA-LET-7A-2 31144 0.0004331 0.0742 0.6061
HSA-LET-7F-2 30884 0.0008048 0.103 0.601
HSA-MIR-628 20837 0.001712 0.137 0.5945
HSA-MIR-205 20906 0.001725 0.137 0.6037
HSA-MIR-1295 17915 0.001868 0.137 0.6077
HSA-MIR-21 30286 0.003027 0.178 0.5894
HSA-MIR-548J 17262 0.003113 0.178 0.6023
HSA-MIR-421 29949 0.005264 0.259 0.5841
Clinical variable #9: 'KARNOFSKY_PERFORMANCE_SCORE'

30 miRs related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 74.03 (16)
  Significant markers N = 30
  pos. correlated 18
  neg. correlated 12
List of top 10 miRs differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

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

SpearmanCorr corrP Q
HSA-MIR-4326 -0.5423 6.366e-06 0.00327
HSA-MIR-107 0.4703 5.926e-05 0.0152
HSA-MIR-181C 0.4372 0.0002162 0.0281
HSA-MIR-26A-2 0.4369 0.0002184 0.0281
HSA-MIR-3691 0.5078 0.0005095 0.0524
HSA-MIR-365-2 -0.3955 0.0009241 0.0792
HSA-MIR-365-1 -0.387 0.001214 0.082
HSA-MIR-1248 -0.3883 0.001276 0.082
HSA-MIR-16-1 0.3794 0.001543 0.0881
HSA-MIR-1304 0.392 0.002136 0.108
Clinical variable #10: 'NUMBER_PACK_YEARS_SMOKED'

No miR related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 34.68 (22)
  Significant markers N = 0
Clinical variable #11: 'RACE'

30 miRs related to 'RACE'.

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

RACE Labels N
  ASIAN 133
  BLACK OR AFRICAN AMERICAN 18
  WHITE 387
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'RACE'

Table S21.  Get Full Table List of top 10 miRs differentially expressed by 'RACE'

kruskal_wallis_P Q
HSA-MIR-3130-1 5.801e-19 2.98e-16
HSA-MIR-412 1.626e-11 4.18e-09
HSA-MIR-4326 1.704e-10 2.92e-08
HSA-MIR-9-3 1.156e-06 0.000148
HSA-MIR-1304 4.143e-06 0.000426
HSA-MIR-149 5.396e-06 0.000462
HSA-MIR-2355 8.536e-06 0.000582
HSA-MIR-423 9.052e-06 0.000582
HSA-MIR-193B 1.871e-05 0.00107
HSA-MIR-34B 2.573e-05 0.00131
Clinical variable #12: 'ETHNICITY'

13 miRs related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 11
  NOT HISPANIC OR LATINO 404
     
  Significant markers N = 13
  Higher in NOT HISPANIC OR LATINO 13
  Higher in HISPANIC OR LATINO 0
List of top 10 miRs differentially expressed by 'ETHNICITY'

Methods & Data
Input

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

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

  • Number of patients = 620

  • Number of miRs = 514

  • 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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