Thyroid Adenocarcinoma: Correlation between miRseq expression and clinical features
(primary solid tumor cohort)
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 532 genes and 13 clinical features across 300 samples, statistically thresholded by Q value < 0.05, 11 clinical features related to at least one genes.

- 4 genes correlated to 'AGE'.

- HSA-MIR-362 , HSA-MIR-874 , HSA-MIR-500A , HSA-MIR-660

- 1 gene correlated to 'GENDER'.

- HSA-MIR-651

- 179 genes correlated to 'HISTOLOGICAL.TYPE'.

- HSA-MIR-21 , HSA-MIR-146B , HSA-MIR-7-2 , HSA-MIR-31 , HSA-MIR-511-1 , ...

- 11 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

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

- 2 genes correlated to 'DISTANT.METASTASIS'.

- HSA-MIR-1270-1 , HSA-MIR-1274B

- 11 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.

- HSA-MIR-21 , HSA-MIR-7-2 , HSA-MIR-204 , HSA-MIR-129-2 , HSA-MIR-1275 , ...

- 24 genes correlated to 'LYMPH.NODE.METASTASIS'.

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

- 22 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

- HSA-MIR-7-2 , HSA-MIR-1179 , HSA-MIR-31 , HSA-MIR-152 , HSA-MIR-146B , ...

- 8 genes correlated to 'NEOPLASM.DISEASESTAGE'.

- HSA-MIR-31 , HSA-MIR-146B , HSA-MIR-375 , HSA-MIR-139 , HSA-MIR-183 , ...

- 1 gene correlated to 'MULTIFOCALITY'.

- HSA-MIR-132

- 8 genes correlated to 'TUMOR.SIZE'.

- HSA-MIR-182 , HSA-MIR-183 , HSA-MIR-136 , HSA-MIR-96 , HSA-MIR-199A-1 , ...

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

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=4 | older | N=4 | younger | N=0
GENDER | t test | N=1 | male | N=0 | female | N=1
HISTOLOGICAL TYPE | ANOVA test | N=179 |  |  |  |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=11 | yes | N=8 | no | N=3
RADIATIONEXPOSURE | t test | N=0 |  |  |  |
DISTANT METASTASIS | ANOVA test | N=2 |  |  |  |
EXTRATHYROIDAL EXTENSION | ANOVA test | N=11 |  |  |  |
LYMPH NODE METASTASIS | ANOVA test | N=24 |  |  |  |
COMPLETENESS OF RESECTION | ANOVA test | N=0 |  |  |  |
NUMBER OF LYMPH NODES | Spearman correlation test | N=22 | higher number.of.lymph.nodes | N=12 | lower number.of.lymph.nodes | N=10
NEOPLASM DISEASESTAGE | ANOVA test | N=8 |  |  |  |
MULTIFOCALITY | t test | N=1 | unifocal | N=0 | multifocal | N=1
TUMOR SIZE | Spearman correlation test | N=8 | higher tumor.size | N=3 | lower tumor.size | N=5

Clinical variable #1: 'AGE'

4 genes related to 'AGE'.

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

AGE | Mean (SD) | 46.55 (15)
| Significant markers | N = 4
| pos. correlated | 4
| neg. correlated | 0

List of 4 genes significantly correlated to 'AGE' by Spearman correlation test

Table S2. Get Full Table List of 4 genes significantly correlated to 'AGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
HSA-MIR-362 | 0.2491 | 1.27e-05 | 0.00676
HSA-MIR-874 | 0.2469 | 1.523e-05 | 0.00808
HSA-MIR-500A | 0.2332 | 4.524e-05 | 0.024
HSA-MIR-660 | 0.225 | 8.428e-05 | 0.0446

Figure S1. Get High-res Image As an example, this figure shows the association of HSA-MIR-362 to 'AGE'. P value = 1.27e-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 | 223
| MALE | 77
| 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 | -4.87 | 3.034e-06 | 0.00161 | 0.688

Figure S2. Get High-res Image As an example, this figure shows the association of HSA-MIR-651 to 'GENDER'. P value = 3.03e-06 with T-test analysis.

Clinical variable #3: 'HISTOLOGICAL.TYPE'

179 genes related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE | Labels | N
| OTHER | 20
| THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL | 172
| THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) | 78
| THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) | 30
| Significant markers | N = 179

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 | 2.668e-40 | 1.42e-37
HSA-MIR-146B | 1.007e-27 | 5.35e-25
HSA-MIR-7-2 | 3.406e-23 | 1.81e-20
HSA-MIR-31 | 2.934e-20 | 1.55e-17
HSA-MIR-511-1 | 8.374e-20 | 4.42e-17
HSA-MIR-152 | 2.32e-19 | 1.22e-16
HSA-MIR-511-2 | 2.372e-19 | 1.25e-16
HSA-MIR-1179 | 4.184e-18 | 2.2e-15
HSA-MIR-3926-1 | 5.739e-17 | 3.01e-14
HSA-MIR-375 | 5.77e-17 | 3.02e-14

Figure S3. Get High-res Image As an example, this figure shows the association of HSA-MIR-21 to 'HISTOLOGICAL.TYPE'. P value = 2.67e-40 with ANOVA analysis.

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

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

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

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 14
| YES | 286
| Significant markers | N = 11
| Higher in YES | 8
| Higher in NO | 3

List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S8. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
HSA-MIR-1269 | 8.14 | 3.586e-10 | 1.88e-07 | 0.8636
HSA-MIR-888 | 7.65 | 4.034e-09 | 2.11e-06 | 0.8315
HSA-MIR-374A | -7.79 | 6.222e-07 | 0.000325 | 0.8851
HSA-MIR-2276 | 7.34 | 1.377e-06 | 0.000719 | 0.8263
HSA-MIR-324 | 7.14 | 1.427e-06 | 0.000743 | 0.8402
HSA-MIR-3130-1 | -6.36 | 1.842e-06 | 0.000958 | 0.7692
HSA-MIR-660 | 6.26 | 1.1e-05 | 0.00571 | 0.8459
HSA-MIR-1976 | 5.82 | 1.97e-05 | 0.0102 | 0.8034
HSA-MIR-20B | 5.73 | 2.891e-05 | 0.0149 | 0.8168
HSA-MIR-652 | 5.57 | 4.191e-05 | 0.0216 | 0.8257

Figure S4. Get High-res Image As an example, this figure shows the association of HSA-MIR-1269 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 3.59e-10 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 | 251
| YES | 13
| Significant markers | N = 0

Clinical variable #6: 'DISTANT.METASTASIS'

2 genes related to 'DISTANT.METASTASIS'.

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

DISTANT.METASTASIS | Labels | N
| M0 | 137
| M1 | 4
| MX | 158
| Significant markers | N = 2

List of 2 genes differentially expressed by 'DISTANT.METASTASIS'

Table S11. Get Full Table List of 2 genes differentially expressed by 'DISTANT.METASTASIS'

| ANOVA_P | Q
--- | --- | ---
HSA-MIR-1270-1 | 8.428e-06 | 0.00448
HSA-MIR-1274B | 3.831e-05 | 0.0203

Figure S5. Get High-res Image As an example, this figure shows the association of HSA-MIR-1270-1 to 'DISTANT.METASTASIS'. P value = 8.43e-06 with ANOVA analysis.

Clinical variable #7: 'EXTRATHYROIDAL.EXTENSION'

11 genes related to 'EXTRATHYROIDAL.EXTENSION'.

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

EXTRATHYROIDAL.EXTENSION | Labels | N
| MINIMAL (T3) | 68
| MODERATE/ADVANCED (T4A) | 6
| NONE | 212
| Significant markers | N = 11

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-21 | 6.091e-07 | 0.000324
HSA-MIR-7-2 | 2.025e-06 | 0.00108
HSA-MIR-204 | 1.203e-05 | 0.00638
HSA-MIR-129-2 | 1.757e-05 | 0.0093
HSA-MIR-1275 | 1.941e-05 | 0.0102
HSA-MIR-539 | 2.304e-05 | 0.0121
HSA-MIR-146B | 2.33e-05 | 0.0123
HSA-MIR-514-3 | 3.998e-05 | 0.021
HSA-MIR-363 | 5.059e-05 | 0.0265
HSA-MIR-514-1 | 7.52e-05 | 0.0393

Figure S6. Get High-res Image As an example, this figure shows the association of HSA-MIR-21 to 'EXTRATHYROIDAL.EXTENSION'. P value = 6.09e-07 with ANOVA analysis.

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

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

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

LYMPH.NODE.METASTASIS | Labels | N
| N0 | 148
| N1 | 17
| N1A | 64
| N1B | 41
| NX | 30
| Significant markers | N = 24

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-7-2 | 5.495e-10 | 2.92e-07
HSA-MIR-146B | 8.924e-10 | 4.74e-07
HSA-MIR-1179 | 1.139e-08 | 6.04e-06
HSA-MIR-31 | 1.618e-08 | 8.56e-06
HSA-MIR-21 | 2.909e-08 | 1.54e-05
HSA-MIR-152 | 4.763e-08 | 2.51e-05
HSA-MIR-551B | 1.195e-07 | 6.29e-05
HSA-MIR-23A | 1.332e-06 | 0.000699
HSA-MIR-204 | 1.624e-06 | 0.000851
HSA-MIR-222 | 1.832e-06 | 0.000958

Figure S7. Get High-res Image As an example, this figure shows the association of HSA-MIR-7-2 to 'LYMPH.NODE.METASTASIS'. P value = 5.5e-10 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 | 238
| R1 | 21
| R2 | 1
| RX | 19
| Significant markers | N = 0

Clinical variable #10: 'NUMBER.OF.LYMPH.NODES'

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

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

NUMBER.OF.LYMPH.NODES | Mean (SD) | 2.77 (5.1)
| Significant markers | N = 22
| pos. correlated | 12
| neg. correlated | 10

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 | -0.4316 | 6.709e-12 | 3.57e-09
HSA-MIR-1179 | -0.3949 | 6.851e-10 | 3.64e-07
HSA-MIR-31 | 0.3387 | 8.48e-08 | 4.49e-05
HSA-MIR-152 | -0.3302 | 1.736e-07 | 9.18e-05
HSA-MIR-146B | 0.3172 | 5.509e-07 | 0.000291
HSA-MIR-21 | 0.2999 | 2.349e-06 | 0.00124
HSA-MIR-19B-1 | 0.2981 | 2.718e-06 | 0.00143
HSA-MIR-23A | 0.2885 | 5.809e-06 | 0.00305
HSA-MIR-204 | -0.2864 | 6.809e-06 | 0.00357
HSA-MIR-7-3 | -0.3197 | 8.682e-06 | 0.00454

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 = 6.71e-12 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'NEOPLASM.DISEASESTAGE'

8 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE | Labels | N
| STAGE I | 169
| STAGE II | 35
| STAGE III | 66
| STAGE IVA | 26
| STAGE IVC | 3
| Significant markers | N = 8

List of 8 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S20. Get Full Table List of 8 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

| ANOVA_P | Q
--- | --- | ---
HSA-MIR-31 | 3.071e-07 | 0.000163
HSA-MIR-146B | 4.743e-06 | 0.00252
HSA-MIR-375 | 1.374e-05 | 0.00728
HSA-MIR-139 | 1.464e-05 | 0.00775
HSA-MIR-183 | 2.304e-05 | 0.0122
HSA-MIR-495 | 3.861e-05 | 0.0203
HSA-MIR-223 | 7.434e-05 | 0.0391
HSA-MIR-376C | 8.471e-05 | 0.0445

Figure S9. Get High-res Image As an example, this figure shows the association of HSA-MIR-31 to 'NEOPLASM.DISEASESTAGE'. P value = 3.07e-07 with ANOVA analysis.

Clinical variable #12: 'MULTIFOCALITY'

One gene related to 'MULTIFOCALITY'.

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

MULTIFOCALITY | Labels | N
| MULTIFOCAL | 148
| UNIFOCAL | 143
| Significant markers | N = 1
| Higher in UNIFOCAL | 0
| Higher in MULTIFOCAL | 1

List of one gene differentially expressed by 'MULTIFOCALITY'

Table S22. Get Full Table List of one gene differentially expressed by 'MULTIFOCALITY'

| T(pos if higher in 'UNIFOCAL') | ttestP | Q | AUC
--- | --- | --- | --- | ---
HSA-MIR-132 | -4.39 | 1.606e-05 | 0.00854 | 0.6495

Figure S10. Get High-res Image As an example, this figure shows the association of HSA-MIR-132 to 'MULTIFOCALITY'. P value = 1.61e-05 with T-test analysis.

Clinical variable #13: 'TUMOR.SIZE'

8 genes related to 'TUMOR.SIZE'.

Table S23. Basic characteristics of clinical feature: 'TUMOR.SIZE'

TUMOR.SIZE | Mean (SD) | 2.68 (1.5)
| Significant markers | N = 8
| pos. correlated | 3
| neg. correlated | 5

List of 8 genes significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

Table S24. Get Full Table List of 8 genes significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
HSA-MIR-182 | 0.3574 | 2.636e-08 | 1.4e-05
HSA-MIR-183 | 0.339 | 1.449e-07 | 7.69e-05
HSA-MIR-136 | -0.3253 | 6.458e-07 | 0.000342
HSA-MIR-96 | 0.3084 | 1.957e-06 | 0.00104
HSA-MIR-199A-1 | -0.3018 | 3.314e-06 | 0.00175
HSA-MIR-199A-2 | -0.2976 | 4.571e-06 | 0.00241
HSA-MIR-199B | -0.2967 | 4.895e-06 | 0.00257
HSA-MIR-1247 | -0.2974 | 8.336e-06 | 0.00438

Figure S11. Get High-res Image As an example, this figure shows the association of HSA-MIR-182 to 'TUMOR.SIZE'. P value = 2.64e-08 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 = 300

- 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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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