Correlation between miRseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1M0447Z
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/C1M0447Z
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 505 miRs and 12 clinical features across 347 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one miRs.

  • 18 miRs correlated to 'AGE'.

    • HSA-MIR-183 ,  HSA-MIR-182 ,  HSA-MIR-96 ,  HSA-MIR-100 ,  HSA-MIR-195 ,  ...

  • 30 miRs correlated to 'NEOPLASM.DISEASESTAGE'.

    • HSA-MIR-199A-1 ,  HSA-MIR-217 ,  HSA-MIR-214 ,  HSA-MIR-199A-2 ,  HSA-MIR-152 ,  ...

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

    • HSA-MIR-217 ,  HSA-MIR-490 ,  HSA-MIR-191 ,  HSA-MIR-16-1 ,  HSA-MIR-100 ,  ...

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

    • HSA-MIR-217 ,  HSA-MIR-320D-1 ,  HSA-MIR-556 ,  HSA-MIR-1249

  • 44 miRs correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-188 ,  HSA-MIR-100 ,  HSA-MIR-33A ,  HSA-MIR-577 ,  HSA-MIR-105-1 ,  ...

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

    • HSA-MIR-628 ,  HSA-LET-7F-2 ,  HSA-LET-7A-2 ,  HSA-LET-7A-1 ,  HSA-LET-7A-3 ,  ...

  • 1 miR correlated to 'NUMBER.OF.LYMPH.NODES'.

    • HSA-MIR-217

  • 14 miRs correlated to 'RACE'.

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

  • No miRs correlated to 'Time to Death', 'PATHOLOGY.M.STAGE', '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=0        
AGE Spearman correlation test N=18 older N=12 younger N=6
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY T STAGE Spearman correlation test N=55 higher stage N=16 lower stage N=39
PATHOLOGY N STAGE Spearman correlation test N=4 higher stage N=1 lower stage N=3
PATHOLOGY M STAGE Kruskal-Wallis test   N=0        
GENDER Wilcoxon test   N=0        
HISTOLOGICAL TYPE Kruskal-Wallis test N=44        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test N=54        
NUMBER OF LYMPH NODES Spearman correlation test N=1 higher number.of.lymph.nodes N=1 lower number.of.lymph.nodes N=0
RACE Kruskal-Wallis test N=14        
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) 0.1-122.3 (median=11.1)
  censored N = 224
  death N = 92
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

18 miRs related to 'AGE'.

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

AGE Mean (SD) 66.07 (11)
  Significant markers N = 18
  pos. correlated 12
  neg. correlated 6
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-183 0.2702 4.25e-07 0.000215
HSA-MIR-182 0.2674 5.637e-07 0.000284
HSA-MIR-96 0.2396 7.938e-06 0.00399
HSA-MIR-100 -0.2356 1.136e-05 0.0057
HSA-MIR-195 -0.2301 1.822e-05 0.00913
HSA-LET-7C -0.2301 1.835e-05 0.00917
HSA-MIR-616 0.2254 3.48e-05 0.0174
HSA-MIR-125B-1 -0.2221 3.607e-05 0.018
HSA-MIR-125B-2 -0.2224 4.231e-05 0.021
HSA-MIR-576 0.2088 0.0001049 0.052
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

30 miRs related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 12
  STAGE IB 38
  STAGE II 28
  STAGE IIA 33
  STAGE IIB 47
  STAGE III 3
  STAGE IIIA 61
  STAGE IIIB 45
  STAGE IIIC 32
  STAGE IV 30
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of top 10 miRs differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
HSA-MIR-199A-1 1.06e-07 5.35e-05
HSA-MIR-217 1.507e-07 7.59e-05
HSA-MIR-214 1.532e-07 7.71e-05
HSA-MIR-199A-2 2.996e-07 0.00015
HSA-MIR-152 3.744e-07 0.000188
HSA-MIR-199B 8.046e-07 0.000402
HSA-MIR-134 1.964e-06 0.00098
HSA-MIR-130A 4.747e-06 0.00236
HSA-MIR-654 5.101e-06 0.00254
HSA-MIR-125B-1 1.248e-05 0.00619
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.88 (0.85)
  N
  1 20
  2 85
  3 147
  4 85
     
  Significant markers N = 55
  pos. correlated 16
  neg. correlated 39
List of top 10 miRs differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7.  Get Full Table List of top 10 miRs significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-217 0.3397 1.618e-10 8.17e-08
HSA-MIR-490 0.2991 5.278e-07 0.000266
HSA-MIR-191 -0.263 9.753e-07 0.000491
HSA-MIR-16-1 -0.2616 1.121e-06 0.000563
HSA-MIR-100 0.2607 1.216e-06 0.000609
HSA-MIR-320B-2 -0.2591 1.425e-06 0.000712
HSA-MIR-132 0.2588 1.472e-06 0.000735
HSA-MIR-556 -0.2746 2.06e-06 0.00103
HSA-MIR-320A -0.2534 2.458e-06 0.00122
HSA-LET-7C 0.251 3.065e-06 0.00152
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 1.26 (1.1)
  N
  0 111
  1 92
  2 66
  3 66
     
  Significant markers N = 4
  pos. correlated 1
  neg. correlated 3
List of 4 miRs differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of 4 miRs significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-217 0.2204 4.851e-05 0.0245
HSA-MIR-320D-1 -0.2428 0.0002214 0.112
HSA-MIR-556 -0.2161 0.0002251 0.113
HSA-MIR-1249 -0.1981 0.0004496 0.226
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
  M0 309
  M1 21
  MX 17
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

No miR related to 'GENDER'.

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

GENDER Labels N
  FEMALE 137
  MALE 210
     
  Significant markers N = 0
Clinical variable #8: 'HISTOLOGICAL.TYPE'

44 miRs related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 62
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 155
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 53
  STOMACH INTESTINAL ADENOCARCINOMA TUBULAR TYPE 45
  STOMACH INTESTINAL ADENOCARCINOMA PAPILLARY TYPE 1
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 20
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 5
  STOMACH ADENOCARCINOMA SIGNET RING TYPE 4
     
  Significant markers N = 44
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'

ANOVA_P Q
HSA-MIR-188 3.302e-07 0.000167
HSA-MIR-100 3.338e-07 0.000168
HSA-MIR-33A 8.617e-07 0.000433
HSA-MIR-577 9.617e-07 0.000483
HSA-MIR-105-1 4.191e-06 0.0021
HSA-MIR-455 4.988e-06 0.00249
HSA-MIR-96 5.548e-06 0.00277
HSA-MIR-192 1.862e-05 0.00927
HSA-MIR-99A 2.857e-05 0.0142
HSA-MIR-532 3.273e-05 0.0162
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 7
  YES 340
     
  Significant markers N = 0
Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

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

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

COMPLETENESS.OF.RESECTION Labels N
  R0 278
  R1 13
  R2 12
  RX 25
     
  Significant markers N = 54
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-MIR-628 2.625e-16 1.33e-13
HSA-LET-7F-2 3.492e-16 1.76e-13
HSA-LET-7A-2 8.285e-15 4.17e-12
HSA-LET-7A-1 1.014e-14 5.09e-12
HSA-LET-7A-3 1.311e-14 6.57e-12
HSA-MIR-26A-1 1.542e-14 7.71e-12
HSA-MIR-361 3.417e-13 1.71e-10
HSA-MIR-3607 1.472e-10 7.33e-08
HSA-MIR-3605 3.208e-10 1.59e-07
HSA-MIR-106A 1.381e-09 6.85e-07
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

One miR related to 'NUMBER.OF.LYMPH.NODES'.

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

NUMBER.OF.LYMPH.NODES Mean (SD) 5.01 (7.2)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one miR differentially expressed by 'NUMBER.OF.LYMPH.NODES'

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

SpearmanCorr corrP Q
HSA-MIR-217 0.2057 0.0002978 0.15
Clinical variable #12: 'RACE'

14 miRs related to 'RACE'.

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

RACE Labels N
  ASIAN 85
  BLACK OR AFRICAN AMERICAN 4
  WHITE 208
     
  Significant markers N = 14
List of top 10 miRs differentially expressed by 'RACE'

Table S20.  Get Full Table List of top 10 miRs differentially expressed by 'RACE'

ANOVA_P Q
HSA-MIR-3130-1 6.256e-14 3.16e-11
HSA-MIR-4326 2.329e-09 1.17e-06
HSA-MIR-412 2.963e-09 1.49e-06
HSA-MIR-103-1 9.979e-07 0.000501
HSA-MIR-423 2.066e-06 0.00104
HSA-MIR-660 3.308e-06 0.00165
HSA-MIR-181A-1 3.764e-06 0.00188
HSA-MIR-93 1.752e-05 0.00872
HSA-MIR-361 3.215e-05 0.016
HSA-MIR-500B 4.113e-05 0.0204
Methods & Data
Input

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

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

  • Number of patients = 347

  • Number of miRs = 505

  • 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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