Correlation between miRseq expression and clinical features
Head and Neck Squamous Cell Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1K35SD5
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/C1K35SD5
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 548 miRs and 13 clinical features across 421 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one miRs.

  • 1 miR correlated to 'NEOPLASM.DISEASESTAGE'.

    • HSA-MIR-139

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

    • HSA-MIR-150 ,  HSA-MIR-137 ,  HSA-MIR-181C ,  HSA-MIR-206

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

    • HSA-LET-7B ,  HSA-MIR-450A-2 ,  HSA-MIR-326 ,  HSA-LET-7A-2 ,  HSA-LET-7A-3 ,  ...

  • 11 miRs correlated to 'GENDER'.

    • HSA-MIR-187 ,  HSA-MIR-15B ,  HSA-MIR-25 ,  HSA-MIR-128-2 ,  HSA-MIR-9-1 ,  ...

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

    • HSA-MIR-660 ,  HSA-MIR-362 ,  HSA-MIR-2355 ,  HSA-MIR-1307 ,  HSA-MIR-340 ,  ...

  • 19 miRs correlated to 'NUMBERPACKYEARSSMOKED'.

    • HSA-MIR-152 ,  HSA-MIR-1180 ,  HSA-MIR-151 ,  HSA-MIR-1266 ,  HSA-MIR-940 ,  ...

  • 10 miRs correlated to 'NUMBER.OF.LYMPH.NODES'.

    • HSA-MIR-421 ,  HSA-MIR-411 ,  HSA-MIR-758 ,  HSA-MIR-151 ,  HSA-MIR-379 ,  ...

  • 1 miR correlated to 'RACE'.

    • HSA-MIR-1304

  • No miRs correlated to 'Time to Death', 'AGE', 'PATHOLOGY.N.STAGE', 'HISTOLOGICAL.TYPE', 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=0        
AGE Spearman correlation test   N=0        
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=1        
PATHOLOGY T STAGE Spearman correlation test N=4 higher stage N=1 lower stage N=3
PATHOLOGY N STAGE Spearman correlation test   N=0        
PATHOLOGY M STAGE Wilcoxon test N=29 mx N=29 m0 N=0
GENDER Wilcoxon test N=11 male N=11 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test   N=0        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=27 yes N=27 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test N=19 higher numberpackyearssmoked N=18 lower numberpackyearssmoked N=1
NUMBER OF LYMPH NODES Spearman correlation test N=10 higher number.of.lymph.nodes N=9 lower number.of.lymph.nodes N=1
RACE Kruskal-Wallis test N=1        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'Time to Death'

No miR related to 'Time to Death'.

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

Time to Death Duration (Years) 2-3837 (median=630)
  censored N = 259
  death N = 100
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No miR related to 'AGE'.

Table S2.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 60.92 (12)
  Significant markers N = 0
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

One miR related to 'NEOPLASM.DISEASESTAGE'.

Table S3.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 24
  STAGE II 63
  STAGE III 70
  STAGE IVA 197
  STAGE IVB 9
     
  Significant markers N = 1
List of one miR differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S4.  Get Full Table List of one miR differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
HSA-MIR-139 0.0003982 0.218
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.85 (1)
  N
  1 40
  2 110
  3 85
  4 133
     
  Significant markers N = 4
  pos. correlated 1
  neg. correlated 3
List of 4 miRs differentially expressed by 'PATHOLOGY.T.STAGE'

Table S6.  Get Full Table List of 4 miRs significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-150 -0.201 0.0001031 0.0565
HSA-MIR-137 0.2296 0.0001826 0.0999
HSA-MIR-181C -0.1871 0.0003083 0.168
HSA-MIR-206 -0.1858 0.0003445 0.188
Clinical variable #5: 'PATHOLOGY.N.STAGE'

No miR related to 'PATHOLOGY.N.STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 1.04 (0.95)
  N
  0 135
  1 56
  2 133
  3 7
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

29 miRs related to 'PATHOLOGY.M.STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 108
  MX 48
     
  Significant markers N = 29
  Higher in MX 29
  Higher in M0 0
List of top 10 miRs differentially expressed by 'PATHOLOGY.M.STAGE'

Table S9.  Get Full Table List of top 10 miRs differentially expressed by 'PATHOLOGY.M.STAGE'

W(pos if higher in 'MX') wilcoxontestP Q AUC
HSA-LET-7B 1334 1.375e-06 0.000754 0.7427
HSA-MIR-450A-2 3770 3.322e-06 0.00182 0.734
HSA-MIR-326 1405 1.04e-05 0.00568 0.7232
HSA-LET-7A-2 1476 1.841e-05 0.01 0.7153
HSA-LET-7A-3 1480 1.973e-05 0.0107 0.7145
HSA-LET-7A-1 1487 2.225e-05 0.0121 0.7132
HSA-MIR-143 1487 2.225e-05 0.0121 0.7132
HSA-MIR-339 3697 2.225e-05 0.0121 0.7132
HSA-MIR-93 3696 2.263e-05 0.0122 0.713
HSA-MIR-450A-1 3629 6.893e-05 0.0372 0.7
Clinical variable #7: 'GENDER'

11 miRs related to 'GENDER'.

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

GENDER Labels N
  FEMALE 123
  MALE 298
     
  Significant markers N = 11
  Higher in MALE 11
  Higher in FEMALE 0
List of top 10 miRs differentially expressed by 'GENDER'

Table S11.  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-187 13593 4.421e-05 0.0242 0.6266
HSA-MIR-15B 22745 9.987e-05 0.0546 0.6205
HSA-MIR-25 22644 0.0001436 0.0784 0.6178
HSA-MIR-128-2 22555 0.0001964 0.107 0.6153
HSA-MIR-9-1 22441 0.000291 0.158 0.6122
HSA-MIR-1180 22432 0.0003001 0.163 0.612
HSA-MIR-9-2 22421 0.0003115 0.169 0.6117
HSA-MIR-130B 22360 0.0003826 0.207 0.61
HSA-MIR-561 5676 0.0003947 0.213 0.6595
HSA-MIR-128-1 22308 0.0004549 0.245 0.6086
Clinical variable #8: 'HISTOLOGICAL.TYPE'

No miR related to 'HISTOLOGICAL.TYPE'.

Table S12.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  HEAD AND NECK SQUAMOUS CELL CARCINOMA 414
  HEAD AND NECK SQUAMOUS CELL CARCINOMA SPINDLE CELL VARIANT 1
  HEAD AND NECK SQUAMOUS CELL CARCINOMA BASALOID TYPE 6
     
  Significant markers N = 0
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S13.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 80
  YES 341
     
  Significant markers N = 27
  Higher in YES 27
  Higher in NO 0
List of top 10 miRs differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S14.  Get Full Table List of top 10 miRs differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
HSA-MIR-660 19956 1.134e-10 6.21e-08 0.7315
HSA-MIR-362 18434 9.88e-07 0.00054 0.6757
HSA-MIR-2355 17975 9.627e-06 0.00526 0.6589
HSA-MIR-1307 17888 1.447e-05 0.00789 0.6557
HSA-MIR-340 9497 2.344e-05 0.0127 0.6519
HSA-LET-7F-2 9627 4.192e-05 0.0228 0.6471
HSA-MIR-34A 17620 4.846e-05 0.0263 0.6459
HSA-MIR-628 9729 6.538e-05 0.0354 0.6434
HSA-MIR-502 17412 0.0001178 0.0636 0.6383
HSA-MIR-143 9904 0.0001368 0.0738 0.637
Clinical variable #10: 'NUMBERPACKYEARSSMOKED'

19 miRs related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 46.67 (38)
  Significant markers N = 19
  pos. correlated 18
  neg. correlated 1
List of top 10 miRs differentially expressed by 'NUMBERPACKYEARSSMOKED'

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

SpearmanCorr corrP Q
HSA-MIR-152 0.3161 6.771e-07 0.000371
HSA-MIR-1180 0.3034 1.948e-06 0.00107
HSA-MIR-151 0.2796 1.248e-05 0.00682
HSA-MIR-1266 0.2807 1.848e-05 0.0101
HSA-MIR-940 0.2729 2.133e-05 0.0116
HSA-MIR-744 0.2699 2.538e-05 0.0138
HSA-MIR-1249 0.2635 4.005e-05 0.0217
HSA-MIR-1224 0.3634 4.197e-05 0.0227
HSA-MIR-3677 0.2582 5.765e-05 0.0311
HSA-MIR-106B 0.2508 9.494e-05 0.0512
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

10 miRs related to 'NUMBER.OF.LYMPH.NODES'.

Table S17.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.31 (4.6)
  Significant markers N = 10
  pos. correlated 9
  neg. correlated 1
List of 10 miRs differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S18.  Get Full Table List of 10 miRs significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-421 0.254 3.897e-06 0.00214
HSA-MIR-411 0.2238 4.832e-05 0.0264
HSA-MIR-758 0.2136 0.0001064 0.0581
HSA-MIR-151 0.2107 0.000133 0.0725
HSA-MIR-379 0.2083 0.0001593 0.0867
HSA-MIR-1293 -0.2064 0.00021 0.114
HSA-MIR-214 0.2009 0.0002738 0.148
HSA-MIR-654 0.1964 0.0003775 0.204
HSA-MIR-127 0.195 0.0004162 0.225
HSA-MIR-143 0.1946 0.0004269 0.23
Clinical variable #12: 'RACE'

One miR related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 10
  BLACK OR AFRICAN AMERICAN 32
  WHITE 366
     
  Significant markers N = 1
List of one miR differentially expressed by 'RACE'

Table S20.  Get Full Table List of one miR differentially expressed by 'RACE'

ANOVA_P Q
HSA-MIR-1304 0.0001192 0.0653
Clinical variable #13: 'ETHNICITY'

No miR related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 18
  NOT HISPANIC OR LATINO 385
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 421

  • Number of miRs = 548

  • Number of clinical features = 13

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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