Correlation between miRseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1348JBH
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/C1348JBH
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 506 miRs and 12 clinical features across 396 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one miRs.

  • 1 miR correlated to 'Time to Death'.

    • HSA-MIR-653

  • 17 miRs correlated to 'AGE'.

    • HSA-MIR-183 ,  HSA-MIR-182 ,  HSA-MIR-96 ,  HSA-LET-7C ,  HSA-MIR-125B-2 ,  ...

  • 29 miRs correlated to 'NEOPLASM.DISEASESTAGE'.

    • HSA-MIR-199A-1 ,  HSA-MIR-152 ,  HSA-MIR-199A-2 ,  HSA-MIR-199B ,  HSA-MIR-214 ,  ...

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

    • HSA-MIR-217 ,  HSA-MIR-320B-2 ,  HSA-MIR-320A ,  HSA-MIR-132 ,  HSA-MIR-191 ,  ...

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

    • HSA-MIR-556 ,  HSA-MIR-33B ,  HSA-MIR-151 ,  HSA-MIR-2277 ,  HSA-MIR-217 ,  ...

  • 1 miR correlated to 'PATHOLOGY.M.STAGE'.

    • HSA-MIR-125A

  • 70 miRs correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-100 ,  HSA-MIR-577 ,  HSA-MIR-105-1 ,  HSA-MIR-99A ,  HSA-MIR-188 ,  ...

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

    • HSA-LET-7F-2 ,  HSA-MIR-628 ,  HSA-MIR-26A-1 ,  HSA-LET-7A-2 ,  HSA-LET-7A-1 ,  ...

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

    • HSA-MIR-3679 ,  HSA-MIR-556 ,  HSA-MIR-151 ,  HSA-MIR-3680 ,  HSA-MIR-1254

  • 12 miRs correlated to 'RACE'.

    • HSA-MIR-3130-1 ,  HSA-MIR-412 ,  HSA-MIR-4326 ,  HSA-MIR-423 ,  HSA-MIR-103-1 ,  ...

  • No miRs correlated to 'GENDER', and 'RADIATIONS.RADIATION.REGIMENINDICATION'.

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=1 shorter survival N=1 longer survival N=0
AGE Spearman correlation test N=17 older N=11 younger N=6
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=29        
PATHOLOGY T STAGE Spearman correlation test N=47 higher stage N=13 lower stage N=34
PATHOLOGY N STAGE Spearman correlation test N=6 higher stage N=1 lower stage N=5
PATHOLOGY M STAGE Kruskal-Wallis test N=1        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL TYPE Kruskal-Wallis test N=70        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=48        
NUMBER OF LYMPH NODES Spearman correlation test N=5 higher number.of.lymph.nodes N=0 lower number.of.lymph.nodes N=5
RACE Kruskal-Wallis test N=12        
Clinical variable #1: 'Time to Death'

One miR related to 'Time to Death'.

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

Time to Death Duration (Months) 0.1-122.3 (median=11.6)
  censored N = 244
  death N = 121
     
  Significant markers N = 1
  associated with shorter survival 1
  associated with longer survival 0
List of one miR differentially expressed by 'Time to Death'

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

HazardRatio Wald_P Q C_index
HSA-MIR-653 1.25 0.0003723 0.19 0.566
Clinical variable #2: 'AGE'

17 miRs related to 'AGE'.

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

AGE Mean (SD) 65.92 (11)
  Significant markers N = 17
  pos. correlated 11
  neg. correlated 6
List of top 10 miRs differentially expressed by 'AGE'

Table S4.  Get Full Table List of top 10 miRs significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-183 0.231 4.132e-06 0.00209
HSA-MIR-182 0.2268 6.266e-06 0.00316
HSA-MIR-96 0.2043 4.913e-05 0.0248
HSA-LET-7C -0.2038 5.119e-05 0.0257
HSA-MIR-125B-2 -0.1995 8.84e-05 0.0444
HSA-MIR-616 0.1965 0.0001156 0.0579
HSA-MIR-592 0.1972 0.0001288 0.0644
HSA-MIR-320D-1 0.2287 2e-04 0.0998
HSA-MIR-99A -0.1862 0.0002214 0.11
HSA-MIR-210 0.1842 0.0002596 0.129
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

29 miRs related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 13
  STAGE IB 39
  STAGE II 32
  STAGE IIA 37
  STAGE IIB 49
  STAGE III 3
  STAGE IIIA 77
  STAGE IIIB 55
  STAGE IIIC 37
  STAGE IV 36
     
  Significant markers N = 29
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'

ANOVA_P Q
HSA-MIR-199A-1 1.327e-07 6.71e-05
HSA-MIR-152 2.253e-07 0.000114
HSA-MIR-199A-2 3.207e-07 0.000162
HSA-MIR-199B 6.826e-07 0.000343
HSA-MIR-214 1.351e-06 0.000678
HSA-MIR-217 4.086e-06 0.00205
HSA-MIR-134 4.586e-06 0.00229
HSA-MIR-130A 5.218e-06 0.0026
HSA-MIR-99B 8.591e-06 0.00428
HSA-MIR-125B-1 2.07e-05 0.0103
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.94 (0.84)
  N
  1 21
  2 87
  3 174
  4 104
     
  Significant markers N = 47
  pos. correlated 13
  neg. correlated 34
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-217 0.2728 5.363e-08 2.71e-05
HSA-MIR-320B-2 -0.2545 4.039e-07 0.000204
HSA-MIR-320A -0.247 8.927e-07 0.00045
HSA-MIR-132 0.2344 3.24e-06 0.00163
HSA-MIR-191 -0.2271 6.579e-06 0.0033
HSA-MIR-16-1 -0.225 8.095e-06 0.00406
HSA-MIR-556 -0.2329 1.667e-05 0.00834
HSA-MIR-7-1 -0.2144 2.15e-05 0.0107
HSA-MIR-182 -0.2128 2.495e-05 0.0124
HSA-MIR-100 0.2124 2.586e-05 0.0129
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 1.28 (1.1)
  N
  0 124
  1 107
  2 75
  3 78
     
  Significant markers N = 6
  pos. correlated 1
  neg. correlated 5
List of 6 miRs differentially expressed by 'PATHOLOGY.N.STAGE'

Table S10.  Get Full Table List of 6 miRs significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-556 -0.229 2.526e-05 0.0128
HSA-MIR-33B -0.1898 0.0002547 0.129
HSA-MIR-151 -0.1827 0.0003187 0.161
HSA-MIR-2277 -0.1931 0.0003408 0.171
HSA-MIR-217 0.1818 0.0003485 0.175
HSA-MIR-320D-1 -0.2156 0.0005129 0.257
Clinical variable #6: 'PATHOLOGY.M.STAGE'

One miR related to 'PATHOLOGY.M.STAGE'.

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 354
  M1 24
  MX 18
     
  Significant markers N = 1
List of one miR differentially expressed by 'PATHOLOGY.M.STAGE'

Table S12.  Get Full Table List of one miR differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
HSA-MIR-125A 0.0005466 0.277
Clinical variable #7: 'GENDER'

No miR related to 'GENDER'.

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

GENDER Labels N
  FEMALE 151
  MALE 245
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL.TYPE'

70 miRs related to 'HISTOLOGICAL.TYPE'.

Table S14.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 65
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 158
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 68
  STOMACH INTESTINAL ADENOCARCINOMA TUBULAR TYPE 64
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 22
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 8
  STOMACH ADENOCARCINOMA SIGNET RING TYPE 9
     
  Significant markers N = 70
List of top 10 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

Table S15.  Get Full Table List of top 10 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
HSA-MIR-100 6.321e-09 3.2e-06
HSA-MIR-577 1.093e-07 5.52e-05
HSA-MIR-105-1 3.555e-07 0.000179
HSA-MIR-99A 6.159e-07 0.00031
HSA-MIR-188 7.555e-07 0.000379
HSA-MIR-455 1.117e-06 0.00056
HSA-MIR-216A 2.047e-06 0.00102
HSA-MIR-96 3.436e-06 0.00171
HSA-MIR-210 3.498e-06 0.00174
HSA-MIR-141 4.451e-06 0.00221
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S16.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 6
  YES 390
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

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

Table S17.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 319
  R1 16
  R2 17
  RX 25
     
  Significant markers N = 48
List of top 10 miRs differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S18.  Get Full Table List of top 10 miRs differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
HSA-LET-7F-2 1.698e-15 8.59e-13
HSA-MIR-628 2.012e-15 1.02e-12
HSA-MIR-26A-1 3.721e-14 1.88e-11
HSA-LET-7A-2 7.826e-14 3.94e-11
HSA-LET-7A-1 9.393e-14 4.72e-11
HSA-LET-7A-3 1.147e-13 5.75e-11
HSA-MIR-361 1.108e-12 5.54e-10
HSA-MIR-3607 9.534e-10 4.76e-07
HSA-MIR-106A 1.945e-09 9.69e-07
HSA-MIR-3605 1.97e-09 9.79e-07
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

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

Table S19.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 5.47 (8.1)
  Significant markers N = 5
  pos. correlated 0
  neg. correlated 5
List of 5 miRs differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S20.  Get Full Table List of 5 miRs significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-3679 -0.3148 5.627e-05 0.0285
HSA-MIR-556 -0.2146 0.0001407 0.0711
HSA-MIR-151 -0.1938 0.0002399 0.121
HSA-MIR-3680 -0.2357 0.0002839 0.143
HSA-MIR-1254 -0.2053 0.000377 0.189
Clinical variable #12: 'RACE'

12 miRs related to 'RACE'.

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

RACE Labels N
  ASIAN 89
  BLACK OR AFRICAN AMERICAN 7
  WHITE 243
     
  Significant markers N = 12
List of top 10 miRs differentially expressed by 'RACE'

Table S22.  Get Full Table List of top 10 miRs differentially expressed by 'RACE'

ANOVA_P Q
HSA-MIR-3130-1 2.608e-13 1.32e-10
HSA-MIR-412 1.092e-09 5.51e-07
HSA-MIR-4326 6.682e-09 3.37e-06
HSA-MIR-423 1.8e-05 0.00906
HSA-MIR-103-1 1.833e-05 0.0092
HSA-MIR-660 4.686e-05 0.0235
HSA-MIR-181A-1 5.927e-05 0.0296
HSA-MIR-361 0.0001137 0.0567
HSA-MIR-93 0.0001904 0.0948
HSA-MIR-500B 0.0002875 0.143
Methods & Data
Input

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

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

  • Number of patients = 396

  • Number of miRs = 506

  • 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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