Correlation between miRseq expression and clinical features
Lung Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C15M64HG
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C15M64HG
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 530 miRs and 14 clinical features across 460 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 'Time to Death'.

    • HSA-MIR-206 ,  HSA-MIR-1911

  • 7 miRs correlated to 'AGE'.

    • HSA-MIR-29C ,  HSA-MIR-130B ,  HSA-MIR-9-2 ,  HSA-MIR-183 ,  HSA-MIR-629 ,  ...

  • 3 miRs correlated to 'NEOPLASM.DISEASESTAGE'.

    • HSA-MIR-30C-2 ,  HSA-MIR-101-2 ,  HSA-MIR-548B

  • 18 miRs correlated to 'PATHOLOGY.T.STAGE'.

    • HSA-MIR-30C-2 ,  HSA-MIR-101-2 ,  HSA-MIR-451 ,  HSA-MIR-146A ,  HSA-MIR-150 ,  ...

  • 5 miRs correlated to 'PATHOLOGY.N.STAGE'.

    • HSA-MIR-548B ,  HSA-MIR-660 ,  HSA-MIR-200A ,  HSA-MIR-200B ,  HSA-MIR-181C

  • 5 miRs correlated to 'PATHOLOGY.M.STAGE'.

    • HSA-MIR-628 ,  HSA-MIR-374A ,  HSA-MIR-16-1 ,  HSA-MIR-424 ,  HSA-MIR-140

  • 7 miRs correlated to 'GENDER'.

    • HSA-MIR-105-2 ,  HSA-MIR-105-1 ,  HSA-MIR-99A ,  HSA-MIR-30E ,  HSA-MIR-361 ,  ...

  • 1 miR correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • HSA-MIR-940

  • 5 miRs correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-130B ,  HSA-MIR-1976 ,  HSA-MIR-656 ,  HSA-MIR-18A ,  HSA-LET-7B

  • 3 miRs correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • HSA-MIR-143 ,  HSA-MIR-181B-2 ,  HSA-MIR-1229

  • 19 miRs correlated to 'NUMBERPACKYEARSSMOKED'.

    • HSA-MIR-339 ,  HSA-MIR-345 ,  HSA-MIR-210 ,  HSA-MIR-296 ,  HSA-MIR-130A ,  ...

  • No miRs correlated to 'COMPLETENESS.OF.RESECTION', 'RACE', 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
Time to Death Cox regression test N=2 shorter survival N=2 longer survival N=0
AGE Spearman correlation test N=7 older N=1 younger N=6
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=3        
PATHOLOGY T STAGE Spearman correlation test N=18 higher stage N=2 lower stage N=16
PATHOLOGY N STAGE Spearman correlation test N=5 higher stage N=0 lower stage N=5
PATHOLOGY M STAGE Kruskal-Wallis test N=5        
GENDER Wilcoxon test N=7 male N=7 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=1 higher score N=0 lower score N=1
HISTOLOGICAL TYPE Kruskal-Wallis test N=5        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=3 yes N=3 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test N=19 higher numberpackyearssmoked N=19 lower numberpackyearssmoked N=0
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test   N=0        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'Time to Death'

2 miRs related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Years) 1-2696 (median=458)
  censored N = 321
  death N = 81
     
  Significant markers N = 2
  associated with shorter survival 2
  associated with longer survival 0
List of 2 miRs differentially expressed by 'Time to Death'

Table S2.  Get Full Table List of 2 miRs significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
HSA-MIR-206 1.4 0.000354 0.19 0.646
HSA-MIR-1911 1.25 0.0003679 0.19 0.646
Clinical variable #2: 'AGE'

7 miRs related to 'AGE'.

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

AGE Mean (SD) 65.57 (9.7)
  Significant markers N = 7
  pos. correlated 1
  neg. correlated 6
List of 7 miRs differentially expressed by 'AGE'

Table S4.  Get Full Table List of 7 miRs significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-29C 0.1812 0.0001587 0.0841
HSA-MIR-130B -0.1786 0.0001976 0.105
HSA-MIR-9-2 -0.1785 0.0001983 0.105
HSA-MIR-183 -0.1776 0.0002136 0.113
HSA-MIR-629 -0.1765 0.0002356 0.124
HSA-MIR-9-1 -0.1759 0.0002463 0.129
HSA-MIR-937 -0.1765 0.0002508 0.131
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

3 miRs related to 'NEOPLASM.DISEASESTAGE'.

Table S5.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 4
  STAGE IA 112
  STAGE IB 132
  STAGE IIA 43
  STAGE IIB 67
  STAGE IIIA 68
  STAGE IIIB 11
  STAGE IV 22
     
  Significant markers N = 3
List of 3 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S6.  Get Full Table List of 3 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
HSA-MIR-30C-2 0.0004979 0.264
HSA-MIR-101-2 0.0005067 0.268
HSA-MIR-548B 0.0005288 0.279
Clinical variable #4: 'PATHOLOGY.T.STAGE'

18 miRs related to 'PATHOLOGY.T.STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 1.86 (0.73)
  N
  1 142
  2 256
  3 41
  4 18
     
  Significant markers N = 18
  pos. correlated 2
  neg. correlated 16
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-30C-2 -0.2189 2.318e-06 0.00123
HSA-MIR-101-2 -0.2088 6.725e-06 0.00356
HSA-MIR-451 -0.2033 1.192e-05 0.00629
HSA-MIR-146A -0.2029 1.24e-05 0.00653
HSA-MIR-150 -0.2011 1.475e-05 0.00776
HSA-MIR-374B -0.1916 3.73e-05 0.0196
HSA-MIR-342 -0.1915 3.787e-05 0.0198
HSA-MIR-218-2 -0.1896 4.525e-05 0.0237
HSA-MIR-486 -0.1831 8.269e-05 0.0432
HSA-MIR-598 -0.1795 0.0001166 0.0607
Clinical variable #5: 'PATHOLOGY.N.STAGE'

5 miRs related to 'PATHOLOGY.N.STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.51 (0.77)
  N
  0 293
  1 84
  2 70
  3 2
     
  Significant markers N = 5
  pos. correlated 0
  neg. correlated 5
List of 5 miRs differentially expressed by 'PATHOLOGY.N.STAGE'

Table S10.  Get Full Table List of 5 miRs significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-548B -0.1878 0.0001102 0.0584
HSA-MIR-660 -0.1735 0.0002203 0.117
HSA-MIR-200A -0.1651 0.0004422 0.233
HSA-MIR-200B -0.164 0.0004838 0.255
HSA-MIR-181C -0.1627 0.0005373 0.283
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
  M0 315
  M1 16
  M1A 1
  M1B 3
  MX 121
     
  Significant markers N = 5
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'

ANOVA_P Q
HSA-MIR-628 1.577e-05 0.00836
HSA-MIR-374A 3.005e-05 0.0159
HSA-MIR-16-1 3.832e-05 0.0202
HSA-MIR-424 5.44e-05 0.0287
HSA-MIR-140 0.0004995 0.263
Clinical variable #7: 'GENDER'

7 miRs related to 'GENDER'.

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

GENDER Labels N
  FEMALE 247
  MALE 213
     
  Significant markers N = 7
  Higher in MALE 7
  Higher in FEMALE 0
List of 7 miRs differentially expressed by 'GENDER'

Table S14.  Get Full Table List of 7 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-105-2 13474 7.434e-07 0.000394 0.6705
HSA-MIR-105-1 13527 2.355e-05 0.0125 0.6437
HSA-MIR-99A 20425 3.534e-05 0.0187 0.6118
HSA-MIR-30E 21025 0.0002041 0.108 0.6004
HSA-MIR-361 21287 0.0004161 0.219 0.5954
HSA-MIR-133A-1 20252 0.0004492 0.236 0.596
HSA-MIR-1247 21036 0.0004775 0.25 0.5947
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

One miR related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S15.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 83.25 (23)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one miR differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S16.  Get Full Table List of one miR significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-940 -0.4161 0.0001366 0.0724
Clinical variable #9: 'HISTOLOGICAL.TYPE'

5 miRs related to 'HISTOLOGICAL.TYPE'.

Table S17.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  LUNG ACINAR ADENOCARCINOMA 13
  LUNG ADENOCARCINOMA MIXED SUBTYPE 92
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 294
  LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS 4
  LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS 19
  LUNG CLEAR CELL ADENOCARCINOMA 2
  LUNG MICROPAPILLARY ADENOCARCINOMA 3
  LUNG MUCINOUS ADENOCARCINOMA 2
  LUNG PAPILLARY ADENOCARCINOMA 19
  LUNG SIGNET RING ADENOCARCINOMA 1
  LUNG SOLID PATTERN PREDOMINANT ADENOCARCINOMA 4
  MUCINOUS (COLLOID) CARCINOMA 7
     
  Significant markers N = 5
List of 5 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

Table S18.  Get Full Table List of 5 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
HSA-MIR-130B 0.0001069 0.0567
HSA-MIR-1976 0.0001344 0.0711
HSA-MIR-656 0.0001562 0.0825
HSA-MIR-18A 0.0003598 0.19
HSA-LET-7B 0.000533 0.28
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

3 miRs related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S19.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 20
  YES 440
     
  Significant markers N = 3
  Higher in YES 3
  Higher in NO 0
List of 3 miRs differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S20.  Get Full Table List of 3 miRs differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
HSA-MIR-143 2251 0.0002197 0.116 0.7442
HSA-MIR-181B-2 6486 0.0003347 0.177 0.737
HSA-MIR-1229 4332 0.0005232 0.276 0.7563
Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

19 miRs related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 42.25 (27)
  Significant markers N = 19
  pos. correlated 19
  neg. correlated 0
List of top 10 miRs differentially expressed by 'NUMBERPACKYEARSSMOKED'

Table S22.  Get Full Table List of top 10 miRs significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-339 0.2557 4.463e-06 0.00237
HSA-MIR-345 0.2548 4.802e-06 0.00254
HSA-MIR-210 0.2543 5.014e-06 0.00265
HSA-MIR-296 0.2491 8.231e-06 0.00434
HSA-MIR-130A 0.2153 0.0001206 0.0634
HSA-MIR-31 0.2202 0.0001232 0.0647
HSA-MIR-590 0.2116 0.000158 0.0828
HSA-MIR-1295 0.2378 0.0001723 0.0901
HSA-MIR-2277 0.2178 0.0001762 0.092
HSA-MIR-106A 0.2045 0.0002637 0.137
Clinical variable #12: 'COMPLETENESS.OF.RESECTION'

No miR related to 'COMPLETENESS.OF.RESECTION'.

Table S23.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 315
  R1 11
  R2 4
  RX 19
     
  Significant markers N = 0
Clinical variable #13: 'RACE'

No miR related to 'RACE'.

Table S24.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 7
  BLACK OR AFRICAN AMERICAN 26
  WHITE 360
     
  Significant markers N = 0
Clinical variable #14: 'ETHNICITY'

No miR related to 'ETHNICITY'.

Table S25.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 7
  NOT HISPANIC OR LATINO 330
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 460

  • Number of miRs = 530

  • Number of clinical features = 14

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

ANOVA analysis

For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R

Student's t-test analysis

For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R

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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[5] 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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