Correlation between miRseq expression and clinical features
Colon Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1D79944
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/C1D79944
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 416 miRs and 12 clinical features across 406 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one miRs.

  • 22 miRs correlated to 'AGE'.

    • HSA-MIR-26A-1 ,  HSA-MIR-432 ,  HSA-MIR-153-2 ,  HSA-MIR-141 ,  HSA-MIR-410 ,  ...

  • 2 miRs correlated to 'NEOPLASM.DISEASESTAGE'.

    • HSA-MIR-625 ,  HSA-MIR-616

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

    • HSA-MIR-501 ,  HSA-MIR-362 ,  HSA-MIR-206

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

    • HSA-MIR-140 ,  HSA-MIR-628 ,  HSA-MIR-142 ,  HSA-MIR-301A ,  HSA-MIR-126 ,  ...

  • 21 miRs correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-592 ,  HSA-MIR-31 ,  HSA-MIR-574 ,  HSA-MIR-552 ,  HSA-MIR-92A-1 ,  ...

  • 57 miRs correlated to 'COMPLETENESS.OF.RESECTION'.

    • HSA-LET-7F-2 ,  HSA-LET-7A-1 ,  HSA-LET-7A-2 ,  HSA-LET-7A-3 ,  HSA-MIR-126 ,  ...

  • 2 miRs correlated to 'RACE'.

    • HSA-MIR-1304 ,  HSA-MIR-412

  • No miRs correlated to 'Time to Death', 'PATHOLOGY.N.STAGE', 'GENDER', 'RADIATIONS.RADIATION.REGIMENINDICATION', and 'NUMBER.OF.LYMPH.NODES'.

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=22 older N=15 younger N=7
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=2        
PATHOLOGY T STAGE Spearman correlation test N=3 higher stage N=0 lower stage N=3
PATHOLOGY N STAGE Spearman correlation test   N=0        
PATHOLOGY M STAGE Kruskal-Wallis test N=25        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL TYPE Wilcoxon test N=21 colon mucinous adenocarcinoma N=21 colon adenocarcinoma N=0
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=57        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=2        
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 (Months) 0.1-140.4 (median=21)
  censored N = 309
  death N = 80
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

22 miRs related to 'AGE'.

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

AGE Mean (SD) 67.35 (13)
  Significant markers N = 22
  pos. correlated 15
  neg. correlated 7
List of top 10 miRs differentially expressed by 'AGE'

Table S3.  Get Full Table List of top 10 miRs significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-26A-1 0.2329 2.149e-06 0.000894
HSA-MIR-432 -0.2346 2.161e-06 0.000897
HSA-MIR-153-2 0.2261 4.321e-06 0.00179
HSA-MIR-141 0.2258 4.463e-06 0.00184
HSA-MIR-410 -0.2052 3.401e-05 0.014
HSA-MIR-653 0.2011 5.674e-05 0.0233
HSA-MIR-34A 0.1982 5.918e-05 0.0243
HSA-MIR-616 0.1969 7.655e-05 0.0313
HSA-MIR-577 0.1948 7.933e-05 0.0324
HSA-MIR-142 0.1945 8.164e-05 0.0332
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

2 miRs related to 'NEOPLASM.DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 66
  STAGE IA 1
  STAGE II 28
  STAGE IIA 120
  STAGE IIB 8
  STAGE IIC 1
  STAGE III 21
  STAGE IIIA 12
  STAGE IIIB 49
  STAGE IIIC 32
  STAGE IV 42
  STAGE IVA 16
  STAGE IVB 1
     
  Significant markers N = 2
List of 2 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of 2 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
HSA-MIR-625 2.684e-05 0.0112
HSA-MIR-616 0.00021 0.0872
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.89 (0.63)
  N
  0 1
  1 10
  2 69
  3 279
  4 46
     
  Significant markers N = 3
  pos. correlated 0
  neg. correlated 3
List of 3 miRs differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7.  Get Full Table List of 3 miRs significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-501 -0.1975 6.285e-05 0.0261
HSA-MIR-362 -0.1735 0.0004534 0.188
HSA-MIR-206 -0.2269 0.0006216 0.257
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.59 (0.77)
  N
  0 239
  1 95
  2 71
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 305
  M1 50
  M1A 7
  M1B 1
  MX 36
     
  Significant markers N = 25
List of top 10 miRs differentially expressed by 'PATHOLOGY.M.STAGE'

Table S10.  Get Full Table List of top 10 miRs differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
HSA-MIR-140 2.072e-06 0.000862
HSA-MIR-628 2.431e-06 0.00101
HSA-MIR-142 4.101e-06 0.0017
HSA-MIR-301A 5.269e-06 0.00218
HSA-MIR-126 1.018e-05 0.00419
HSA-MIR-1180 1.038e-05 0.00427
HSA-MIR-455 1.127e-05 0.00462
HSA-MIR-106A 1.243e-05 0.00508
HSA-MIR-616 1.45e-05 0.00592
HSA-LET-7F-2 1.716e-05 0.00698
Clinical variable #7: 'GENDER'

No miR related to 'GENDER'.

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

GENDER Labels N
  FEMALE 191
  MALE 215
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL.TYPE'

21 miRs related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 351
  COLON MUCINOUS ADENOCARCINOMA 53
     
  Significant markers N = 21
  Higher in COLON MUCINOUS ADENOCARCINOMA 21
  Higher in COLON ADENOCARCINOMA 0
List of top 10 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

Table S13.  Get Full Table List of top 10 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

W(pos if higher in 'COLON MUCINOUS ADENOCARCINOMA') wilcoxontestP Q AUC
HSA-MIR-592 4710 1.97e-08 8.2e-06 0.7412
HSA-MIR-31 13176 6.114e-08 2.54e-05 0.7312
HSA-MIR-574 13099 1.652e-06 0.000684 0.7041
HSA-MIR-552 5555 2.272e-06 0.000938 0.7014
HSA-MIR-92A-1 5635 3.717e-06 0.00153 0.6971
HSA-MIR-196B 5796 9.714e-06 0.00399 0.6884
HSA-MIR-1247 5823 1.137e-05 0.00466 0.687
HSA-MIR-29A 5895 1.72e-05 0.00703 0.6831
HSA-MIR-92A-2 5951 2.36e-05 0.00963 0.6801
HSA-MIR-98 6179 8.146e-05 0.0332 0.6678
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No miR related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S14.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 3
  YES 403
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

57 miRs related to 'COMPLETENESS.OF.RESECTION'.

Table S15.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 282
  R1 3
  R2 25
  RX 22
     
  Significant markers N = 57
List of top 10 miRs differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S16.  Get Full Table List of top 10 miRs differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
HSA-LET-7F-2 3.704e-07 0.000154
HSA-LET-7A-1 4.394e-07 0.000182
HSA-LET-7A-2 4.592e-07 0.00019
HSA-LET-7A-3 5.326e-07 0.00022
HSA-MIR-126 5.683e-07 0.000234
HSA-MIR-199B 7.502e-07 0.000308
HSA-MIR-16-1 8.694e-07 0.000356
HSA-MIR-1180 8.74e-07 0.000357
HSA-MIR-136 9.51e-07 0.000388
HSA-MIR-497 1.497e-06 0.000609
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

No miR related to 'NUMBER.OF.LYMPH.NODES'.

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

NUMBER.OF.LYMPH.NODES Mean (SD) 2.05 (4.5)
  Significant markers N = 0
Clinical variable #12: 'RACE'

2 miRs related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 11
  BLACK OR AFRICAN AMERICAN 23
  WHITE 213
     
  Significant markers N = 2
List of 2 miRs differentially expressed by 'RACE'

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

ANOVA_P Q
HSA-MIR-1304 1.338e-05 0.00557
HSA-MIR-412 0.0004194 0.174
Methods & Data
Input

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

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

  • Number of patients = 406

  • Number of miRs = 416

  • Number of clinical features = 12

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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