Thyroid Adenocarcinoma: Correlation between miRseq expression and clinical features
Maintained by Juok Cho (Broad Institute)
Overview
Introduction

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

Summary

Testing the association between 531 genes and 5 clinical features across 210 samples, statistically thresholded by Q value < 0.05, 4 clinical features related to at least one genes.

  • 5 genes correlated to 'AGE'.

    • HSA-MIR-874 ,  HSA-MIR-362 ,  HSA-MIR-500A ,  HSA-MIR-1229 ,  HSA-MIR-152

  • 108 genes correlated to 'HISTOLOGICAL.TYPE'.

    • HSA-MIR-21 ,  HSA-MIR-146B ,  HSA-MIR-7-2 ,  HSA-MIR-31 ,  HSA-MIR-152 ,  ...

  • 10 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • HSA-MIR-1269 ,  HSA-MIR-888 ,  HSA-MIR-374A ,  HSA-MIR-3130-1 ,  HSA-MIR-324 ,  ...

  • 3 genes correlated to 'NEOADJUVANT.THERAPY'.

    • HSA-MIR-9-1 ,  HSA-MIR-424 ,  HSA-MIR-129-1

  • No genes correlated to 'GENDER'

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 genes that are significantly associated with each clinical feature at Q value < 0.05.

Clinical feature Statistical test Significant genes Associated with                 Associated with
AGE Spearman correlation test N=5 older N=5 younger N=0
GENDER t test   N=0        
HISTOLOGICAL TYPE ANOVA test N=108        
RADIATIONS RADIATION REGIMENINDICATION t test N=10 yes N=8 no N=2
NEOADJUVANT THERAPY t test N=3 yes N=2 no N=1
Clinical variable #1: 'AGE'

5 genes related to 'AGE'.

Table S1.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 46.6 (16)
  Significant markers N = 5
  pos. correlated 5
  neg. correlated 0
List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

Table S2.  Get Full Table List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-874 0.3264 1.332e-06 0.000707
HSA-MIR-362 0.2904 1.904e-05 0.0101
HSA-MIR-500A 0.2869 2.418e-05 0.0128
HSA-MIR-1229 0.2845 9.088e-05 0.048
HSA-MIR-152 0.2663 9.361e-05 0.0493

Figure S1.  Get High-res Image As an example, this figure shows the association of HSA-MIR-874 to 'AGE'. P value = 1.33e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 155
  MALE 55
     
  Significant markers N = 0
Clinical variable #3: 'HISTOLOGICAL.TYPE'

108 genes related to 'HISTOLOGICAL.TYPE'.

Table S4.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  OTHER 8
  THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL 116
  THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) 64
  THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) 22
     
  Significant markers N = 108
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
HSA-MIR-21 1.615e-26 8.58e-24
HSA-MIR-146B 2.124e-17 1.13e-14
HSA-MIR-7-2 7.643e-17 4.04e-14
HSA-MIR-31 1.99e-15 1.05e-12
HSA-MIR-152 3.367e-14 1.77e-11
HSA-MIR-3926-1 4.425e-13 2.33e-10
HSA-MIR-1179 1.688e-12 8.86e-10
HSA-MIR-30C-2 3.353e-12 1.76e-09
HSA-MIR-204 3.663e-12 1.92e-09
HSA-MIR-511-1 4.908e-12 2.56e-09

Figure S2.  Get High-res Image As an example, this figure shows the association of HSA-MIR-21 to 'HISTOLOGICAL.TYPE'. P value = 1.62e-26 with ANOVA analysis.

Clinical variable #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

10 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S6.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 14
  YES 196
     
  Significant markers N = 10
  Higher in YES 8
  Higher in NO 2
List of 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S7.  Get Full Table List of 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
HSA-MIR-1269 6.86 1.228e-08 6.43e-06 0.8656
HSA-MIR-888 6.37 6.913e-08 3.62e-05 0.8256
HSA-MIR-374A -7.22 5.909e-07 0.000308 0.8535
HSA-MIR-3130-1 -6.07 1.924e-06 0.001 0.7775
HSA-MIR-324 6.38 2.643e-06 0.00137 0.8065
HSA-MIR-2276 6.16 2.941e-06 0.00153 0.783
HSA-MIR-1976 5.71 1.724e-05 0.00893 0.8105
HSA-MIR-660 5.56 2.584e-05 0.0134 0.8156
HSA-MIR-20B 5.32 3.979e-05 0.0205 0.7912
HSA-MIR-652 5.19 6.415e-05 0.033 0.8072

Figure S3.  Get High-res Image As an example, this figure shows the association of HSA-MIR-1269 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.23e-08 with T-test analysis.

Clinical variable #5: 'NEOADJUVANT.THERAPY'

3 genes related to 'NEOADJUVANT.THERAPY'.

Table S8.  Basic characteristics of clinical feature: 'NEOADJUVANT.THERAPY'

NEOADJUVANT.THERAPY Labels N
  NO 3
  YES 207
     
  Significant markers N = 3
  Higher in YES 2
  Higher in NO 1
List of 3 genes differentially expressed by 'NEOADJUVANT.THERAPY'

Table S9.  Get Full Table List of 3 genes differentially expressed by 'NEOADJUVANT.THERAPY'

T(pos if higher in 'YES') ttestP Q AUC
HSA-MIR-9-1 9.53 1.337e-09 5.07e-07 0.7971
HSA-MIR-424 -10.13 1.489e-07 5.63e-05 0.8422
HSA-MIR-129-1 13.84 2.342e-06 0.000883 0.9125

Figure S4.  Get High-res Image As an example, this figure shows the association of HSA-MIR-9-1 to 'NEOADJUVANT.THERAPY'. P value = 1.34e-09 with T-test analysis.

Methods & Data
Input

  • Expresson data file = THCA.miRseq_RPKM_log2.txt

  • Clinical data file = THCA.clin.merged.picked.txt

  • Number of patients = 210

  • Number of genes = 531

  • Number of clinical features = 5

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References
[1] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] 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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