Correlation between miRseq expression and clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C14Q7T04
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/C14Q7T04
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 572 miRs and 12 clinical features across 391 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 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • HSA-MIR-125B-2 ,  HSA-MIR-337 ,  HSA-LET-7C ,  HSA-MIR-101-2 ,  HSA-MIR-152 ,  ...

  • 30 miRs correlated to 'YEARS_TO_BIRTH'.

    • HSA-MIR-552 ,  HSA-MIR-377 ,  HSA-MIR-337 ,  HSA-MIR-493 ,  HSA-MIR-214 ,  ...

  • 30 miRs correlated to 'NEOPLASM_DISEASESTAGE'.

    • HSA-MIR-199A-2 ,  HSA-MIR-199A-1 ,  HSA-MIR-141 ,  HSA-MIR-199B ,  HSA-MIR-200C ,  ...

  • 30 miRs correlated to 'PATHOLOGY_T_STAGE'.

    • HSA-MIR-199A-2 ,  HSA-MIR-199B ,  HSA-MIR-199A-1 ,  HSA-MIR-99A ,  HSA-MIR-214 ,  ...

  • 30 miRs correlated to 'PATHOLOGY_N_STAGE'.

    • HSA-MIR-100 ,  HSA-MIR-125B-1 ,  HSA-MIR-99A ,  HSA-MIR-582 ,  HSA-MIR-125B-2 ,  ...

  • 15 miRs correlated to 'PATHOLOGY_M_STAGE'.

    • HSA-MIR-140 ,  HSA-MIR-215 ,  HSA-MIR-329-2 ,  HSA-MIR-3614 ,  HSA-LET-7F-2 ,  ...

  • 11 miRs correlated to 'GENDER'.

    • HSA-MIR-223 ,  HSA-MIR-29A ,  HSA-MIR-329-1 ,  HSA-MIR-369 ,  HSA-MIR-152 ,  ...

  • 30 miRs correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

    • HSA-MIR-338 ,  HSA-MIR-30E ,  HSA-MIR-101-1 ,  HSA-MIR-146B ,  HSA-MIR-598 ,  ...

  • 30 miRs correlated to 'NUMBER_OF_LYMPH_NODES'.

    • HSA-MIR-100 ,  HSA-MIR-125B-1 ,  HSA-MIR-545 ,  HSA-MIR-99A ,  HSA-MIR-944 ,  ...

  • 30 miRs correlated to 'RACE'.

    • HSA-MIR-664 ,  HSA-MIR-598 ,  HSA-MIR-30D ,  HSA-MIR-212 ,  HSA-MIR-200C ,  ...

  • No miRs correlated to 'NUMBER_PACK_YEARS_SMOKED', and 'ETHNICITY'.

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=30 shorter survival N=24 longer survival N=6
YEARS_TO_BIRTH Spearman correlation test N=30 older N=26 younger N=4
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=23 lower stage N=7
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=12 lower stage N=18
PATHOLOGY_M_STAGE Wilcoxon test N=15 class1 N=15 class0 N=0
GENDER Wilcoxon test N=11 male N=11 female N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test N=30 higher score N=6 lower score N=24
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=11 lower number_of_lymph_nodes N=19
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

30 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) 0.1-166 (median=15.6)
  censored N = 235
  death N = 155
     
  Significant markers N = 30
  associated with shorter survival 24
  associated with longer survival 6
List of top 10 miRs differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 miRs significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
HSA-MIR-125B-2 1.18 0.0001959 0.078 0.59
HSA-MIR-337 1.23 0.000391 0.078 0.593
HSA-LET-7C 1.2 0.0005229 0.078 0.575
HSA-MIR-101-2 0.71 0.000776 0.078 0.436
HSA-MIR-152 1.34 0.0007943 0.078 0.581
HSA-MIR-379 1.22 0.000823 0.078 0.573
HSA-MIR-134 1.21 0.001106 0.083 0.581
HSA-MIR-654 1.18 0.001184 0.083 0.582
HSA-MIR-758 1.18 0.001428 0.083 0.574
HSA-MIR-1538 1.44 0.001679 0.083 0.614
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) 67.74 (11)
  Significant markers N = 30
  pos. correlated 26
  neg. correlated 4
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-552 -0.2977 1.767e-05 0.00301
HSA-MIR-377 0.2146 2.457e-05 0.00301
HSA-MIR-337 0.2112 2.601e-05 0.00301
HSA-MIR-493 0.2093 3.093e-05 0.00301
HSA-MIR-214 0.2074 3.651e-05 0.00301
HSA-MIR-127 0.2071 3.772e-05 0.00301
HSA-MIR-376B 0.2103 3.964e-05 0.00301
HSA-MIR-10A -0.2058 4.205e-05 0.00301
HSA-MIR-494 0.2118 5.232e-05 0.0032
HSA-MIR-320B-2 -0.2007 6.591e-05 0.0032
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 miRs related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 4
  STAGE II 126
  STAGE III 127
  STAGE IV 129
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'NEOPLASM_DISEASESTAGE'

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

kruskal_wallis_P Q
HSA-MIR-199A-2 1.036e-09 4e-07
HSA-MIR-199A-1 1.398e-09 4e-07
HSA-MIR-141 3.591e-09 5.54e-07
HSA-MIR-199B 3.873e-09 5.54e-07
HSA-MIR-200C 1.345e-08 1.54e-06
HSA-MIR-99A 1.944e-08 1.85e-06
HSA-MIR-214 2.345e-08 1.92e-06
HSA-MIR-100 2.993e-08 2.14e-06
HSA-MIR-1245 3.595e-08 2.28e-06
HSA-MIR-125B-1 4.424e-08 2.53e-06
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 (0.72)
  N
  T0 2
  T1 3
  T2 117
  T3 184
  T4 53
     
  Significant markers N = 30
  pos. correlated 23
  neg. correlated 7
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-199A-2 0.3087 2.292e-09 7.82e-07
HSA-MIR-199B 0.3052 3.557e-09 7.82e-07
HSA-MIR-199A-1 0.304 4.102e-09 7.82e-07
HSA-MIR-99A 0.275 1.186e-07 1.23e-05
HSA-MIR-214 0.2739 1.341e-07 1.23e-05
HSA-MIR-200C -0.2735 1.407e-07 1.23e-05
HSA-MIR-127 0.2729 1.502e-07 1.23e-05
HSA-MIR-382 0.2694 2.175e-07 1.56e-05
HSA-MIR-411 0.2687 2.549e-07 1.62e-05
HSA-MIR-493 0.2658 3.222e-07 1.84e-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) 0.62 (0.9)
  N
  N0 226
  N1 41
  N2 76
  N3 8
     
  Significant markers N = 30
  pos. correlated 12
  neg. correlated 18
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-100 0.2728 2.097e-07 0.00012
HSA-MIR-125B-1 0.2611 7.055e-07 0.000202
HSA-MIR-99A 0.2546 1.351e-06 0.000258
HSA-MIR-582 -0.2306 1.279e-05 0.00183
HSA-MIR-125B-2 0.2276 2.194e-05 0.00229
HSA-MIR-944 -0.2247 2.398e-05 0.00229
HSA-MIR-199A-2 0.2206 3.055e-05 0.00229
HSA-LET-7C 0.22 3.197e-05 0.00229
HSA-MIR-199A-1 0.2156 4.627e-05 0.00294
HSA-MIR-199B 0.2134 5.572e-05 0.00319
Clinical variable #6: 'PATHOLOGY_M_STAGE'

15 miRs related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 188
  class1 10
     
  Significant markers N = 15
  Higher in class1 15
  Higher in class0 0
List of top 10 miRs differentially expressed by 'PATHOLOGY_M_STAGE'

Table S12.  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-140 359 0.00101 0.216 0.809
HSA-MIR-215 364 0.001163 0.216 0.8053
HSA-MIR-329-2 181 0.001329 0.216 0.8384
HSA-MIR-3614 375 0.001507 0.216 0.7984
HSA-LET-7F-2 393 0.001967 0.225 0.791
HSA-MIR-330 432 0.00405 0.289 0.7702
HSA-LET-7F-1 438 0.004508 0.289 0.767
HSA-MIR-10B 439 0.004589 0.289 0.7665
HSA-MIR-1249 359 0.004718 0.289 0.7796
HSA-MIR-26A-2 452 0.005763 0.289 0.7596
Clinical variable #7: 'GENDER'

11 miRs related to 'GENDER'.

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

GENDER Labels N
  FEMALE 101
  MALE 290
     
  Significant markers N = 11
  Higher in MALE 11
  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-223 11270 0.0005609 0.177 0.6152
HSA-MIR-29A 11459 0.001128 0.177 0.6088
HSA-MIR-329-1 6852 0.001359 0.177 0.6196
HSA-MIR-369 11535 0.001709 0.177 0.6048
HSA-MIR-152 11599 0.001849 0.177 0.604
HSA-MIR-376C 11647 0.002181 0.177 0.6024
HSA-MIR-410 11634 0.002404 0.177 0.6014
HSA-MIR-651 11704 0.002646 0.177 0.6004
HSA-MIR-655 10773 0.00278 0.177 0.6019
HSA-MIR-196A-2 9430 0.004581 0.262 0.5999
Clinical variable #8: 'KARNOFSKY_PERFORMANCE_SCORE'

30 miRs related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 82.78 (14)
  Significant markers N = 30
  pos. correlated 6
  neg. correlated 24
List of top 10 miRs differentially expressed by 'KARNOFSKY_PERFORMANCE_SCORE'

Table S16.  Get Full Table List of top 10 miRs significantly correlated to 'KARNOFSKY_PERFORMANCE_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-338 0.3899 6.375e-06 0.00365
HSA-MIR-30E -0.3738 1.618e-05 0.00463
HSA-MIR-101-1 -0.3557 4.36e-05 0.00831
HSA-MIR-146B 0.3436 8.198e-05 0.00839
HSA-MIR-598 -0.3422 8.78e-05 0.00839
HSA-MIR-3655 -0.5258 8.805e-05 0.00839
HSA-MIR-200C -0.3338 0.0001336 0.0109
HSA-MIR-151 -0.3305 0.0001573 0.0112
HSA-MIR-200B -0.3279 0.0001785 0.0112
HSA-MIR-29C -0.326 0.000195 0.0112
Clinical variable #9: 'NUMBER_PACK_YEARS_SMOKED'

No miR related to 'NUMBER_PACK_YEARS_SMOKED'.

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

NUMBER_PACK_YEARS_SMOKED Mean (SD) 39 (54)
  Significant markers N = 0
Clinical variable #10: 'NUMBER_OF_LYMPH_NODES'

30 miRs related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 2.03 (6.9)
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 miRs differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S19.  Get Full Table List of top 10 miRs significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-100 0.2393 4.751e-05 0.0142
HSA-MIR-125B-1 0.2386 5.009e-05 0.0142
HSA-MIR-545 -0.2514 7.438e-05 0.0142
HSA-MIR-99A 0.2237 0.0001476 0.0211
HSA-MIR-944 -0.2153 0.0002916 0.0334
HSA-MIR-3662 -0.2435 0.0005822 0.0555
HSA-MIR-125B-2 0.195 0.001104 0.0866
HSA-MIR-1976 -0.1914 0.001212 0.0866
HSA-LET-7C 0.1876 0.001524 0.0969
HSA-MIR-455 -0.1832 0.001971 0.103
Clinical variable #11: 'RACE'

30 miRs related to 'RACE'.

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

RACE Labels N
  ASIAN 43
  BLACK OR AFRICAN AMERICAN 22
  WHITE 309
     
  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-664 4.828e-10 2.76e-07
HSA-MIR-598 1.803e-09 5e-07
HSA-MIR-30D 2.62e-09 5e-07
HSA-MIR-212 2.179e-08 3.12e-06
HSA-MIR-200C 2.891e-08 3.12e-06
HSA-MIR-320A 3.277e-08 3.12e-06
HSA-MIR-29C 5.391e-08 4.4e-06
HSA-MIR-200B 1.013e-07 7.24e-06
HSA-MIR-30E 1.7e-07 1.08e-05
HSA-MIR-200A 2.826e-07 1.48e-05
Clinical variable #12: 'ETHNICITY'

No miR related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 9
  NOT HISPANIC OR LATINO 352
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 391

  • Number of miRs = 572

  • 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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