Correlation between miRseq expression and clinical features
Thyroid Adenocarcinoma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1F18WZS
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1F18WZS
Overview
Introduction

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

Summary

Testing the association between 532 genes and 13 clinical features across 282 samples, statistically thresholded by Q value < 0.05, 10 clinical features related to at least one genes.

  • 3 genes correlated to 'AGE'.

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

  • 1 gene correlated to 'GENDER'.

    • HSA-MIR-651

  • 170 genes correlated to 'HISTOLOGICAL.TYPE'.

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

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

    • HSA-MIR-1269 ,  HSA-MIR-888 ,  HSA-MIR-374A ,  HSA-MIR-2276 ,  HSA-MIR-324 ,  ...

  • 1 gene correlated to 'DISTANT.METASTASIS'.

    • HSA-MIR-1270-1

  • 13 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.

    • HSA-MIR-129-2 ,  HSA-MIR-21 ,  HSA-MIR-7-2 ,  HSA-MIR-204 ,  HSA-MIR-514B ,  ...

  • 18 genes correlated to 'LYMPH.NODE.METASTASIS'.

    • HSA-MIR-146B ,  HSA-MIR-7-2 ,  HSA-MIR-31 ,  HSA-MIR-21 ,  HSA-MIR-1179 ,  ...

  • 19 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • HSA-MIR-7-2 ,  HSA-MIR-1179 ,  HSA-MIR-31 ,  HSA-MIR-152 ,  HSA-MIR-19B-1 ,  ...

  • 6 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • HSA-MIR-31 ,  HSA-MIR-146B ,  HSA-MIR-139 ,  HSA-MIR-183 ,  HSA-MIR-154 ,  ...

  • 7 genes correlated to 'TUMOR.SIZE'.

    • HSA-MIR-182 ,  HSA-MIR-136 ,  HSA-MIR-183 ,  HSA-MIR-96 ,  HSA-MIR-1247 ,  ...

  • No genes correlated to 'RADIATIONEXPOSURE', 'COMPLETENESS.OF.RESECTION', and 'MULTIFOCALITY'.

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=3 older N=3 younger N=0
GENDER t test N=1 male N=0 female N=1
HISTOLOGICAL TYPE ANOVA test N=170        
RADIATIONS RADIATION REGIMENINDICATION t test N=10 yes N=8 no N=2
RADIATIONEXPOSURE t test   N=0        
DISTANT METASTASIS ANOVA test N=1        
EXTRATHYROIDAL EXTENSION ANOVA test N=13        
LYMPH NODE METASTASIS ANOVA test N=18        
COMPLETENESS OF RESECTION ANOVA test   N=0        
NUMBER OF LYMPH NODES Spearman correlation test N=19 higher number.of.lymph.nodes N=12 lower number.of.lymph.nodes N=7
NEOPLASM DISEASESTAGE ANOVA test N=6        
MULTIFOCALITY t test   N=0        
TUMOR SIZE Spearman correlation test N=7 higher tumor.size N=3 lower tumor.size N=4
Clinical variable #1: 'AGE'

3 genes related to 'AGE'.

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

AGE Mean (SD) 46.59 (15)
  Significant markers N = 3
  pos. correlated 3
  neg. correlated 0
List of 3 genes significantly correlated to 'AGE' by Spearman correlation test

Table S2.  Get Full Table List of 3 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-874 0.2566 1.28e-05 0.00681
HSA-MIR-362 0.254 1.573e-05 0.00835
HSA-MIR-500A 0.2449 3.204e-05 0.017

Figure S1.  Get High-res Image As an example, this figure shows the association of HSA-MIR-874 to 'AGE'. P value = 1.28e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'GENDER'

One gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 207
  MALE 75
     
  Significant markers N = 1
  Higher in MALE 0
  Higher in FEMALE 1
List of one gene differentially expressed by 'GENDER'

Table S4.  Get Full Table List of one gene differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
HSA-MIR-651 -4.48 1.588e-05 0.00845 0.6755

Figure S2.  Get High-res Image As an example, this figure shows the association of HSA-MIR-651 to 'GENDER'. P value = 1.59e-05 with T-test analysis.

Clinical variable #3: 'HISTOLOGICAL.TYPE'

170 genes related to 'HISTOLOGICAL.TYPE'.

Table S5.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  OTHER 18
  THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL 162
  THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) 72
  THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) 30
     
  Significant markers N = 170
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
HSA-MIR-21 6.382e-37 3.4e-34
HSA-MIR-146B 8.731e-25 4.64e-22
HSA-MIR-7-2 2.171e-20 1.15e-17
HSA-MIR-152 1.553e-19 8.22e-17
HSA-MIR-31 2.134e-19 1.13e-16
HSA-MIR-3926-1 9.11e-18 4.8e-15
HSA-MIR-511-1 4.637e-17 2.44e-14
HSA-MIR-345 3.083e-16 1.62e-13
HSA-MIR-1179 6.156e-16 3.23e-13
HSA-MIR-30C-2 8.215e-16 4.3e-13

Figure S3.  Get High-res Image As an example, this figure shows the association of HSA-MIR-21 to 'HISTOLOGICAL.TYPE'. P value = 6.38e-37 with ANOVA analysis.

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

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

Table S7.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 14
  YES 268
     
  Significant markers N = 10
  Higher in YES 8
  Higher in NO 2
List of 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S8.  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 7.66 1.371e-09 7.2e-07 0.8554
HSA-MIR-888 7.36 5.717e-09 3e-06 0.822
HSA-MIR-374A -7.56 8.024e-07 0.00042 0.8777
HSA-MIR-2276 7.08 1.337e-06 0.000698 0.8169
HSA-MIR-324 7.04 1.502e-06 0.000782 0.8369
HSA-MIR-3130-1 -6.08 3.245e-06 0.00169 0.7588
HSA-MIR-1976 6.05 1.215e-05 0.0063 0.818
HSA-MIR-660 6.15 1.247e-05 0.00646 0.8401
HSA-MIR-20B 5.64 3.142e-05 0.0162 0.8103
HSA-MIR-652 5.57 4.032e-05 0.0208 0.8273

Figure S4.  Get High-res Image As an example, this figure shows the association of HSA-MIR-1269 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.37e-09 with T-test analysis.

Clinical variable #5: 'RADIATIONEXPOSURE'

No gene related to 'RADIATIONEXPOSURE'.

Table S9.  Basic characteristics of clinical feature: 'RADIATIONEXPOSURE'

RADIATIONEXPOSURE Labels N
  NO 235
  YES 11
     
  Significant markers N = 0
Clinical variable #6: 'DISTANT.METASTASIS'

One gene related to 'DISTANT.METASTASIS'.

Table S10.  Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS Labels N
  M0 120
  M1 4
  MX 157
     
  Significant markers N = 1
List of one gene differentially expressed by 'DISTANT.METASTASIS'

Table S11.  Get Full Table List of one gene differentially expressed by 'DISTANT.METASTASIS'

ANOVA_P Q
HSA-MIR-1270-1 1.359e-05 0.00723

Figure S5.  Get High-res Image As an example, this figure shows the association of HSA-MIR-1270-1 to 'DISTANT.METASTASIS'. P value = 1.36e-05 with ANOVA analysis.

Clinical variable #7: 'EXTRATHYROIDAL.EXTENSION'

13 genes related to 'EXTRATHYROIDAL.EXTENSION'.

Table S12.  Basic characteristics of clinical feature: 'EXTRATHYROIDAL.EXTENSION'

EXTRATHYROIDAL.EXTENSION Labels N
  MINIMAL (T3) 63
  MODERATE/ADVANCED (T4A) 5
  NONE 200
     
  Significant markers N = 13
List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

ANOVA_P Q
HSA-MIR-129-2 1.107e-06 0.000589
HSA-MIR-21 1.275e-06 0.000677
HSA-MIR-7-2 7.781e-06 0.00412
HSA-MIR-204 1.713e-05 0.00906
HSA-MIR-514B 1.799e-05 0.0095
HSA-MIR-514-3 2.038e-05 0.0107
HSA-MIR-514-1 2.607e-05 0.0137
HSA-MIR-514-2 3.547e-05 0.0186
HSA-MIR-1275 5.207e-05 0.0273
HSA-MIR-146B 6.094e-05 0.0319

Figure S6.  Get High-res Image As an example, this figure shows the association of HSA-MIR-129-2 to 'EXTRATHYROIDAL.EXTENSION'. P value = 1.11e-06 with ANOVA analysis.

Clinical variable #8: 'LYMPH.NODE.METASTASIS'

18 genes related to 'LYMPH.NODE.METASTASIS'.

Table S14.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 137
  N1 15
  N1A 62
  N1B 39
  NX 29
     
  Significant markers N = 18
List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
HSA-MIR-146B 1.116e-08 5.94e-06
HSA-MIR-7-2 2.03e-08 1.08e-05
HSA-MIR-31 9.81e-08 5.2e-05
HSA-MIR-21 1.096e-07 5.8e-05
HSA-MIR-1179 1.414e-07 7.46e-05
HSA-MIR-152 2.397e-07 0.000126
HSA-MIR-551B 1.134e-06 0.000597
HSA-MIR-142 4.404e-06 0.00231
HSA-MIR-222 6.098e-06 0.0032
HSA-MIR-511-2 1.244e-05 0.00651

Figure S7.  Get High-res Image As an example, this figure shows the association of HSA-MIR-146B to 'LYMPH.NODE.METASTASIS'. P value = 1.12e-08 with ANOVA analysis.

Clinical variable #9: 'COMPLETENESS.OF.RESECTION'

No gene related to 'COMPLETENESS.OF.RESECTION'.

Table S16.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 221
  R1 20
  R2 1
  RX 19
     
  Significant markers N = 0
Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

19 genes related to 'NUMBER.OF.LYMPH.NODES'.

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

NUMBER.OF.LYMPH.NODES Mean (SD) 2.82 (5.2)
  Significant markers N = 19
  pos. correlated 12
  neg. correlated 7
List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S18.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-7-2 -0.4109 3.622e-10 1.93e-07
HSA-MIR-1179 -0.3855 6.989e-09 3.71e-06
HSA-MIR-31 0.3483 9.894e-08 5.24e-05
HSA-MIR-152 -0.3313 4.135e-07 0.000219
HSA-MIR-19B-1 0.3114 2.103e-06 0.00111
HSA-MIR-146B 0.3107 2.228e-06 0.00117
HSA-MIR-21 0.2999 5.133e-06 0.0027
HSA-MIR-222 0.2904 1.043e-05 0.00548
HSA-MIR-139 -0.282 1.919e-05 0.0101
HSA-MIR-7-3 -0.3164 1.995e-05 0.0104

Figure S8.  Get High-res Image As an example, this figure shows the association of HSA-MIR-7-2 to 'NUMBER.OF.LYMPH.NODES'. P value = 3.62e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'NEOPLASM.DISEASESTAGE'

6 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S19.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 158
  STAGE II 34
  STAGE III 62
  STAGE IVA 24
  STAGE IVC 3
     
  Significant markers N = 6
List of 6 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S20.  Get Full Table List of 6 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
HSA-MIR-31 3.604e-06 0.00192
HSA-MIR-146B 3.365e-05 0.0179
HSA-MIR-139 3.766e-05 0.02
HSA-MIR-183 4.878e-05 0.0258
HSA-MIR-154 7.903e-05 0.0417
HSA-MIR-223 8.64e-05 0.0455

Figure S9.  Get High-res Image As an example, this figure shows the association of HSA-MIR-31 to 'NEOPLASM.DISEASESTAGE'. P value = 3.6e-06 with ANOVA analysis.

Clinical variable #12: 'MULTIFOCALITY'

No gene related to 'MULTIFOCALITY'.

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

MULTIFOCALITY Labels N
  MULTIFOCAL 138
  UNIFOCAL 135
     
  Significant markers N = 0
Clinical variable #13: 'TUMOR.SIZE'

7 genes related to 'TUMOR.SIZE'.

Table S22.  Basic characteristics of clinical feature: 'TUMOR.SIZE'

TUMOR.SIZE Mean (SD) 2.77 (1.5)
  Significant markers N = 7
  pos. correlated 3
  neg. correlated 4
List of 7 genes significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

Table S23.  Get Full Table List of 7 genes significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-182 0.3074 5.098e-06 0.00271
HSA-MIR-136 -0.3045 7.786e-06 0.00413
HSA-MIR-183 0.2939 1.357e-05 0.00719
HSA-MIR-96 0.2808 3.342e-05 0.0177
HSA-MIR-1247 -0.281 5.316e-05 0.0281
HSA-MIR-199A-1 -0.2733 5.513e-05 0.0291
HSA-MIR-199A-2 -0.2665 8.526e-05 0.0448

Figure S10.  Get High-res Image As an example, this figure shows the association of HSA-MIR-182 to 'TUMOR.SIZE'. P value = 5.1e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

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

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

  • Number of patients = 282

  • Number of genes = 532

  • Number of clinical features = 13

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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