Correlation between miRseq expression and clinical features
Liver Hepatocellular Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1WM1CGJ
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/C1WM1CGJ
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 544 miRs and 11 clinical features across 358 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one miRs.

  • 30 miRs correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • HSA-MIR-149 ,  HSA-MIR-3677 ,  HSA-MIR-23C ,  HSA-MIR-489 ,  HSA-MIR-632 ,  ...

  • 30 miRs correlated to 'YEARS_TO_BIRTH'.

    • HSA-MIR-1269 ,  HSA-MIR-200C ,  HSA-MIR-483 ,  HSA-MIR-412 ,  HSA-MIR-296 ,  ...

  • 22 miRs correlated to 'NEOPLASM_DISEASESTAGE'.

    • HSA-MIR-23C ,  HSA-MIR-550A-1 ,  HSA-MIR-139 ,  HSA-MIR-7-2 ,  HSA-MIR-642A ,  ...

  • 30 miRs correlated to 'PATHOLOGY_T_STAGE'.

    • HSA-MIR-23C ,  HSA-MIR-139 ,  HSA-MIR-550A-1 ,  HSA-MIR-149 ,  HSA-MIR-122 ,  ...

  • 30 miRs correlated to 'GENDER'.

    • HSA-MIR-26A-2 ,  HSA-MIR-375 ,  HSA-MIR-1301 ,  HSA-MIR-331 ,  HSA-MIR-106A ,  ...

  • 30 miRs correlated to 'HISTOLOGICAL_TYPE'.

    • HSA-MIR-194-1 ,  HSA-MIR-194-2 ,  HSA-MIR-192 ,  HSA-MIR-10A ,  HSA-MIR-122 ,  ...

  • 30 miRs correlated to 'RACE'.

    • HSA-MIR-23C ,  HSA-MIR-3130-1 ,  HSA-MIR-532 ,  HSA-MIR-30D ,  HSA-MIR-511-1 ,  ...

  • 2 miRs correlated to 'ETHNICITY'.

    • HSA-MIR-508 ,  HSA-MIR-514-3

  • No miRs correlated to 'PATHOLOGY_N_STAGE', 'PATHOLOGY_M_STAGE', and 'COMPLETENESS_OF_RESECTION'.

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=28 longer survival N=2
YEARS_TO_BIRTH Spearman correlation test N=30 older N=5 younger N=25
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=22        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=24 lower stage N=6
PATHOLOGY_N_STAGE Wilcoxon test   N=0        
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test N=30 male N=30 female N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
COMPLETENESS_OF_RESECTION Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test N=2 not hispanic or latino N=2 hispanic or latino 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) 0-120.8 (median=19.3)
  censored N = 251
  death N = 106
     
  Significant markers N = 30
  associated with shorter survival 28
  associated with longer survival 2
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-149 1.37 3.833e-06 0.0021 0.63
HSA-MIR-3677 1.41 1.856e-05 0.005 0.644
HSA-MIR-23C 0.74 2.781e-05 0.005 0.394
HSA-MIR-489 1.56 6.341e-05 0.0056 0.635
HSA-MIR-632 1.71 7.506e-05 0.0056 0.6
HSA-MIR-9-1 1.18 7.826e-05 0.0056 0.62
HSA-MIR-9-2 1.18 7.996e-05 0.0056 0.618
HSA-MIR-212 1.48 8.239e-05 0.0056 0.617
HSA-MIR-550A-1 1.5 0.0001366 0.0082 0.609
HSA-MIR-106A 1.33 0.0001792 0.0082 0.586
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) 59.57 (13)
  Significant markers N = 30
  pos. correlated 5
  neg. correlated 25
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-1269 0.2607 7.352e-07 4e-04
HSA-MIR-200C -0.2287 1.356e-05 0.00369
HSA-MIR-483 -0.2244 2.211e-05 0.00401
HSA-MIR-412 -0.2207 3.724e-05 0.00439
HSA-MIR-296 -0.2226 4.036e-05 0.00439
HSA-MIR-181B-1 -0.2138 4.902e-05 0.00444
HSA-MIR-181A-2 -0.2109 6.2e-05 0.00481
HSA-MIR-181D -0.2093 7.072e-05 0.00481
HSA-LET-7E -0.2078 8.022e-05 0.00485
HSA-MIR-889 -0.1985 0.0001711 0.00931
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

22 miRs related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 166
  STAGE II 83
  STAGE III 3
  STAGE IIIA 61
  STAGE IIIB 8
  STAGE IIIC 9
  STAGE IV 3
  STAGE IVA 1
  STAGE IVB 2
     
  Significant markers N = 22
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-23C 7.392e-05 0.0402
HSA-MIR-550A-1 0.0001764 0.048
HSA-MIR-139 0.0003543 0.0551
HSA-MIR-7-2 0.0004049 0.0551
HSA-MIR-642A 0.0006008 0.0654
HSA-MIR-194-1 0.001025 0.0902
HSA-MIR-194-2 0.001161 0.0902
HSA-MIR-550A-2 0.002507 0.17
HSA-MIR-22 0.003189 0.193
HSA-MIR-346 0.003862 0.196
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) 1.79 (0.91)
  N
  T0 1
  T1 176
  T2 90
  T3 76
  T4 13
     
  Significant markers N = 30
  pos. correlated 24
  neg. correlated 6
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-23C -0.289 1.63e-07 4.85e-05
HSA-MIR-139 -0.2724 1.784e-07 4.85e-05
HSA-MIR-550A-1 0.2634 4.767e-07 8.64e-05
HSA-MIR-149 0.2345 8.009e-06 0.00109
HSA-MIR-122 -0.2268 1.562e-05 0.00143
HSA-MIR-22 -0.2264 1.615e-05 0.00143
HSA-MIR-194-1 -0.2239 2.003e-05 0.00143
HSA-MIR-194-2 -0.2234 2.1e-05 0.00143
HSA-MIR-550A-2 0.2195 3.019e-05 0.00182
HSA-MIR-7-3 0.2846 0.000103 0.0056
Clinical variable #5: 'PATHOLOGY_N_STAGE'

No miR related to 'PATHOLOGY_N_STAGE'.

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

PATHOLOGY_N_STAGE Labels N
  N0 249
  N1 4
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY_M_STAGE'

No miR related to 'PATHOLOGY_M_STAGE'.

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

PATHOLOGY_M_STAGE Labels N
  class0 263
  class1 4
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

30 miRs related to 'GENDER'.

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

GENDER Labels N
  FEMALE 113
  MALE 245
     
  Significant markers N = 30
  Higher in MALE 30
  Higher in FEMALE 0
List of top 10 miRs differentially expressed by 'GENDER'

Table S12.  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-26A-2 9933 1.745e-05 0.00557 0.6412
HSA-MIR-375 10024 2.726e-05 0.00557 0.6379
HSA-MIR-1301 10106 4.041e-05 0.00557 0.635
HSA-MIR-331 10109 4.099e-05 0.00557 0.6349
HSA-MIR-106A 10216 6.769e-05 0.00736 0.631
HSA-MIR-363 10455 0.0001979 0.0125 0.6224
HSA-MIR-182 10464 0.0002058 0.0125 0.622
HSA-MIR-26A-1 10200 0.0002108 0.0125 0.6223
HSA-MIR-1266 10444 0.0002293 0.0125 0.6212
HSA-MIR-183 10490 0.0002303 0.0125 0.6211
Clinical variable #8: 'HISTOLOGICAL_TYPE'

30 miRs related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  FIBROLAMELLAR CARCINOMA 2
  HEPATOCELLULAR CARCINOMA 349
  HEPATOCHOLANGIOCARCINOMA (MIXED) 7
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'HISTOLOGICAL_TYPE'

Table S14.  Get Full Table List of top 10 miRs differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
HSA-MIR-194-1 0.0002901 0.0763
HSA-MIR-194-2 0.0003852 0.0763
HSA-MIR-192 0.0004207 0.0763
HSA-MIR-10A 0.0009435 0.106
HSA-MIR-122 0.0009786 0.106
HSA-MIR-200B 0.001607 0.146
HSA-MIR-200A 0.002081 0.149
HSA-MIR-101-1 0.002192 0.149
HSA-MIR-375 0.002682 0.162
HSA-MIR-214 0.003181 0.164
Clinical variable #9: 'COMPLETENESS_OF_RESECTION'

No miR related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 315
  R1 15
  R2 1
  RX 20
     
  Significant markers N = 0
Clinical variable #10: 'RACE'

30 miRs related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 159
  BLACK OR AFRICAN AMERICAN 17
  WHITE 171
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'RACE'

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

kruskal_wallis_P Q
HSA-MIR-23C 5.315e-15 2.89e-12
HSA-MIR-3130-1 2.502e-11 6.81e-09
HSA-MIR-532 4.404e-07 7.99e-05
HSA-MIR-30D 1.22e-06 0.000166
HSA-MIR-511-1 1.186e-05 0.00104
HSA-MIR-1304 1.277e-05 0.00104
HSA-MIR-511-2 1.339e-05 0.00104
HSA-MIR-338 5.639e-05 0.00366
HSA-MIR-26B 6.048e-05 0.00366
HSA-MIR-627 8.05e-05 0.00438
Clinical variable #11: 'ETHNICITY'

2 miRs related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 12
  NOT HISPANIC OR LATINO 329
     
  Significant markers N = 2
  Higher in NOT HISPANIC OR LATINO 2
  Higher in HISPANIC OR LATINO 0
List of 2 miRs differentially expressed by 'ETHNICITY'

Table S19.  Get Full Table List of 2 miRs differentially expressed by 'ETHNICITY'

W(pos if higher in 'NOT HISPANIC OR LATINO') wilcoxontestP Q AUC
HSA-MIR-508 c("3148", "0.0003382") c("3148", "0.0003382") 0.184 0.8047
HSA-MIR-514-3 c("1409", "0.0009128") c("1409", "0.0009128") 0.248 0.8963
Methods & Data
Input

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

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

  • Number of patients = 358

  • Number of miRs = 544

  • Number of clinical features = 11

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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