Correlation between miRseq expression and clinical features
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1TB159F
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/C1TB159F
Overview
Introduction

This pipeline uses various statistical tests to identify miRs whose expression levels correlated to selected clinical features.

Summary

Testing the association between 539 miRs and 9 clinical features across 78 samples, statistically thresholded by Q value < 0.05, 4 clinical features related to at least one miRs.

  • 1 miR correlated to 'AGE'.

    • HSA-MIR-424

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

    • HSA-MIR-202 ,  HSA-MIR-514-1 ,  HSA-MIR-514-3 ,  HSA-MIR-514-2 ,  HSA-MIR-509-3 ,  ...

  • 11 miRs correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-205 ,  HSA-MIR-944 ,  HSA-MIR-194-2 ,  HSA-MIR-192 ,  HSA-MIR-194-1 ,  ...

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

    • HSA-MIR-338 ,  HSA-MIR-660 ,  HSA-MIR-532 ,  HSA-MIR-362

  • No miRs correlated to 'Time to Death', 'PATHOLOGY.T.STAGE', 'PATHOLOGY.N.STAGE', 'NUMBERPACKYEARSSMOKED', 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 Q value < 0.05.

Clinical feature Statistical test Significant miRs Associated with                 Associated with
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=1 older N=0 younger N=1
PATHOLOGY T STAGE Spearman correlation test   N=0        
PATHOLOGY N STAGE t test   N=0        
PATHOLOGY M STAGE ANOVA test N=6        
HISTOLOGICAL TYPE ANOVA test N=11        
RADIATIONS RADIATION REGIMENINDICATION t test N=4 yes N=4 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
NUMBER OF LYMPH NODES Spearman correlation 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 (Months) 0.1-177 (median=10.1)
  censored N = 62
  death N = 14
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

One miR related to 'AGE'.

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

AGE Mean (SD) 48.09 (13)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one miR significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of one miR significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-424 -0.4656 1.984e-05 0.0107

Figure S1.  Get High-res Image As an example, this figure shows the association of HSA-MIR-424 to 'AGE'. P value = 1.98e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'PATHOLOGY.T.STAGE'

No miR related to 'PATHOLOGY.T.STAGE'.

Table S4.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 1.41 (0.66)
  N
  1 49
  2 22
  3 1
  4 2
     
  Significant markers N = 0
Clinical variable #4: 'PATHOLOGY.N.STAGE'

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

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Labels N
  class0 49
  class1 24
     
  Significant markers N = 0
Clinical variable #5: 'PATHOLOGY.M.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 48
  M1 2
  MX 23
     
  Significant markers N = 6
List of 6 miRs differentially expressed by 'PATHOLOGY.M.STAGE'

Table S7.  Get Full Table List of 6 miRs differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
HSA-MIR-202 5.325e-07 0.000287
HSA-MIR-514-1 2.612e-05 0.0141
HSA-MIR-514-3 5.878e-05 0.0316
HSA-MIR-514-2 6.079e-05 0.0326
HSA-MIR-509-3 6.346e-05 0.034
HSA-MIR-452 8.615e-05 0.046

Figure S2.  Get High-res Image As an example, this figure shows the association of HSA-MIR-202 to 'PATHOLOGY.M.STAGE'. P value = 5.32e-07 with ANOVA analysis.

Clinical variable #6: 'HISTOLOGICAL.TYPE'

11 miRs related to 'HISTOLOGICAL.TYPE'.

Table S8.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  CERVICAL SQUAMOUS CELL CARCINOMA 67
  ENDOCERVICAL ADENOCARCINOMA OF THE USUAL TYPE 1
  ENDOCERVICAL TYPE OF ADENOCARCINOMA 8
  ENDOMETRIOID ADENOCARCINOMA OF ENDOCERVIX 1
  MUCINOUS ADENOCARCINOMA OF ENDOCERVICAL TYPE 1
     
  Significant markers N = 11
List of top 10 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

Table S9.  Get Full Table List of top 10 miRs differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
HSA-MIR-205 2.464e-19 1.32e-16
HSA-MIR-944 3.302e-15 1.77e-12
HSA-MIR-194-2 9.301e-15 4.98e-12
HSA-MIR-192 1.71e-14 9.13e-12
HSA-MIR-194-1 2.291e-13 1.22e-10
HSA-MIR-375 3.566e-07 0.00019
HSA-MIR-10A 2.367e-06 0.00126
HSA-MIR-215 5.668e-06 0.003
HSA-MIR-449A 2.611e-05 0.0138
HSA-MIR-155 2.892e-05 0.0153

Figure S3.  Get High-res Image As an example, this figure shows the association of HSA-MIR-205 to 'HISTOLOGICAL.TYPE'. P value = 2.46e-19 with ANOVA analysis.

Clinical variable #7: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S10.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 17
  YES 61
     
  Significant markers N = 4
  Higher in YES 4
  Higher in NO 0
List of 4 miRs differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S11.  Get Full Table List of 4 miRs differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
HSA-MIR-338 5.09 1.263e-05 0.00678 0.8245
HSA-MIR-660 5.21 2.116e-05 0.0113 0.8467
HSA-MIR-532 4.79 4.653e-05 0.0249 0.811
HSA-MIR-362 4.47 9.061e-05 0.0484 0.8014

Figure S4.  Get High-res Image As an example, this figure shows the association of HSA-MIR-338 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.26e-05 with T-test analysis.

Clinical variable #8: 'NUMBERPACKYEARSSMOKED'

No miR related to 'NUMBERPACKYEARSSMOKED'.

Table S12.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 19.24 (13)
  Significant markers N = 0
Clinical variable #9: 'NUMBER.OF.LYMPH.NODES'

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

Table S13.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 0.98 (2.4)
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 78

  • Number of miRs = 539

  • Number of clinical features = 9

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

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

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

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