Thyroid Adenocarcinoma: Correlation between mRNAseq expression and clinical features
(primary solid tumor cohort)
Maintained by Juok Cho (Broad Institute)
Overview
Introduction

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

Summary

Testing the association between 18025 genes and 13 clinical features across 289 samples, statistically thresholded by Q value < 0.05, 13 clinical features related to at least one genes.

  • 64 genes correlated to 'AGE'.

    • C12ORF52|84934 ,  DDX28|55794 ,  DDIT4L|115265 ,  ZNF518B|85460 ,  EPN3|55040 ,  ...

  • 38 genes correlated to 'GENDER'.

    • DDX3Y|8653 ,  RPS4Y1|6192 ,  ZFY|7544 ,  UTY|7404 ,  USP9Y|8287 ,  ...

  • 5588 genes correlated to 'HISTOLOGICAL.TYPE'.

    • FN1|2335 ,  KCNN4|3783 ,  FAM176A|84141 ,  GABRB2|2561 ,  LDLR|3949 ,  ...

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

    • FLJ37543|285668 ,  C14ORF180|400258 ,  TAS2R43|259289 ,  A2ML1|144568 ,  HPR|3250 ,  ...

  • 14 genes correlated to 'RADIATIONEXPOSURE'.

    • CRNN|49860 ,  C13ORF30|144809 ,  FAM138F|641702 ,  P2RX2|22953 ,  RPRML|388394 ,  ...

  • 23 genes correlated to 'DISTANT.METASTASIS'.

    • ARRB1|408 ,  RTN4RL1|146760 ,  GJA5|2702 ,  APOL3|80833 ,  CYP21A2|1589 ,  ...

  • 120 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.

    • PLRG1|5356 ,  FOXJ1|2302 ,  CYP26A1|1592 ,  TSPYL5|85453 ,  VEGFA|7422 ,  ...

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

    • KCNN4|3783 ,  CREB5|9586 ,  TACSTD2|4070 ,  CLCNKA|1187 ,  FN1|2335 ,  ...

  • 3 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • CATSPER2P1|440278 ,  MUC13|56667 ,  TRIM72|493829

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

    • PCDP1|200373 ,  FAM60A|58516 ,  SPATS2L|26010 ,  DIO2|1734 ,  TMEM117|84216 ,  ...

  • 133 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • CYP26A1|1592 ,  SEMA3G|56920 ,  GOT2|2806 ,  KIAA1383|54627 ,  AIFM1|9131 ,  ...

  • 2 genes correlated to 'MULTIFOCALITY'.

    • INMT|11185 ,  ETS1|2113

  • 14 genes correlated to 'TUMOR.SIZE'.

    • LRRC55|219527 ,  ABCA6|23460 ,  CLDN2|9075 ,  LSM12|124801 ,  PTGS1|5742 ,  ...

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=64 older N=33 younger N=31
GENDER t test N=38 male N=15 female N=23
HISTOLOGICAL TYPE ANOVA test N=5588        
RADIATIONS RADIATION REGIMENINDICATION t test N=35 yes N=19 no N=16
RADIATIONEXPOSURE t test N=14 yes N=2 no N=12
DISTANT METASTASIS ANOVA test N=23        
EXTRATHYROIDAL EXTENSION ANOVA test N=120        
LYMPH NODE METASTASIS ANOVA test N=638        
COMPLETENESS OF RESECTION ANOVA test N=3        
NUMBER OF LYMPH NODES Spearman correlation test N=539 higher number.of.lymph.nodes N=250 lower number.of.lymph.nodes N=289
NEOPLASM DISEASESTAGE ANOVA test N=133        
MULTIFOCALITY t test N=2 unifocal N=0 multifocal N=2
TUMOR SIZE Spearman correlation test N=14 higher tumor.size N=2 lower tumor.size N=12
Clinical variable #1: 'AGE'

64 genes related to 'AGE'.

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

AGE Mean (SD) 46.65 (15)
  Significant markers N = 64
  pos. correlated 33
  neg. correlated 31
List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S2.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
C12ORF52|84934 0.3622 2.194e-10 3.95e-06
DDX28|55794 0.3562 4.51e-10 8.13e-06
DDIT4L|115265 0.3346 5.456e-09 9.83e-05
ZNF518B|85460 -0.3309 8.238e-09 0.000148
EPN3|55040 0.3277 1.169e-08 0.000211
IL20RA|53832 0.3247 1.695e-08 0.000305
ASB13|79754 0.314 4.931e-08 0.000889
TUBGCP5|114791 0.3112 6.601e-08 0.00119
RAB3A|5864 0.3059 1.127e-07 0.00203
GPI|2821 0.303 1.498e-07 0.0027

Figure S1.  Get High-res Image As an example, this figure shows the association of C12ORF52|84934 to 'AGE'. P value = 2.19e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'GENDER'

38 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 216
  MALE 73
     
  Significant markers N = 38
  Higher in MALE 15
  Higher in FEMALE 23
List of top 10 genes differentially expressed by 'GENDER'

Table S4.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
DDX3Y|8653 86.65 1.047e-130 1.89e-126 1
RPS4Y1|6192 72.09 3.735e-129 6.73e-125 1
ZFY|7544 80.03 1.312e-128 2.36e-124 1
UTY|7404 81.48 2.648e-105 4.77e-101 1
USP9Y|8287 74.82 1.229e-99 2.21e-95 1
NLGN4Y|22829 54.67 1.607e-97 2.9e-93 1
PRKY|5616 34.39 1.143e-91 2.06e-87 0.9985
KDM5D|8284 77.32 1.641e-90 2.96e-86 1
CYORF15A|246126 62.49 4.944e-61 8.91e-57 1
XIST|7503 -38.75 1.619e-54 2.92e-50 0.9992

Figure S2.  Get High-res Image As an example, this figure shows the association of DDX3Y|8653 to 'GENDER'. P value = 1.05e-130 with T-test analysis.

Clinical variable #3: 'HISTOLOGICAL.TYPE'

5588 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 169
  THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) 73
  THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) 29
     
  Significant markers N = 5588
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
FN1|2335 8.806e-45 1.59e-40
KCNN4|3783 3.793e-42 6.84e-38
FAM176A|84141 3.78e-41 6.81e-37
GABRB2|2561 2.18e-39 3.93e-35
LDLR|3949 2.345e-39 4.23e-35
SYT12|91683 4.302e-39 7.75e-35
PTPRE|5791 2.093e-38 3.77e-34
SFTPB|6439 3.396e-38 6.12e-34
CREB5|9586 8.93e-38 1.61e-33
FLJ42709|441094 1.603e-37 2.89e-33

Figure S3.  Get High-res Image As an example, this figure shows the association of FN1|2335 to 'HISTOLOGICAL.TYPE'. P value = 8.81e-45 with ANOVA analysis.

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

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

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 12
  YES 277
     
  Significant markers N = 35
  Higher in YES 19
  Higher in NO 16
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
FLJ37543|285668 12.79 9.988e-15 1.79e-10 0.8746
C14ORF180|400258 10.81 2.442e-14 4.38e-10 0.8603
TAS2R43|259289 8.52 1.842e-10 3.31e-06 0.7764
A2ML1|144568 9.45 4.812e-10 8.64e-06 0.8071
HPR|3250 8.79 2.191e-09 3.93e-05 0.9126
HCFC1|3054 -10.85 3.456e-09 6.2e-05 0.9116
LOC440173|440173 7.93 1.251e-08 0.000224 0.8759
ARHGEF18|23370 -7.98 5.333e-08 0.000957 0.8069
TMEM218|219854 8.7 1.015e-07 0.00182 0.8565
C5ORF60|285679 6.89 1.06e-07 0.0019 0.778

Figure S4.  Get High-res Image As an example, this figure shows the association of FLJ37543|285668 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 9.99e-15 with T-test analysis.

Clinical variable #5: 'RADIATIONEXPOSURE'

14 genes related to 'RADIATIONEXPOSURE'.

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

RADIATIONEXPOSURE Labels N
  NO 241
  YES 12
     
  Significant markers N = 14
  Higher in YES 2
  Higher in NO 12
List of top 10 genes differentially expressed by 'RADIATIONEXPOSURE'

Table S10.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONEXPOSURE'

T(pos if higher in 'YES') ttestP Q AUC
CRNN|49860 -10.61 2.115e-17 3.8e-13 0.913
C13ORF30|144809 -9.35 7.017e-15 1.26e-10 0.8462
FAM138F|641702 -8.95 6.565e-14 1.18e-09 0.8222
P2RX2|22953 -8.37 1.984e-12 3.56e-08 0.8904
RPRML|388394 -7.52 8.537e-11 1.53e-06 0.8049
SLCO1A2|6579 -7.89 1.038e-10 1.87e-06 0.8109
OR9A4|130075 -7.76 2.856e-10 5.13e-06 0.8294
CSNK1A1P|161635 -7.07 9.747e-10 1.75e-05 0.8214
SLC12A1|6557 -8.27 4.863e-09 8.73e-05 0.8333
CYORF15A|246126 5.84 9.261e-08 0.00166 0.6265

Figure S5.  Get High-res Image As an example, this figure shows the association of CRNN|49860 to 'RADIATIONEXPOSURE'. P value = 2.12e-17 with T-test analysis.

Clinical variable #6: 'DISTANT.METASTASIS'

23 genes related to 'DISTANT.METASTASIS'.

Table S11.  Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS Labels N
  M0 140
  M1 4
  MX 144
     
  Significant markers N = 23
List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

ANOVA_P Q
ARRB1|408 2.201e-09 3.97e-05
RTN4RL1|146760 1.013e-08 0.000183
GJA5|2702 3.016e-08 0.000544
APOL3|80833 4.137e-08 0.000746
CYP21A2|1589 6.53e-08 0.00118
PTPRR|5801 1.401e-07 0.00252
DPEP2|64174 1.644e-07 0.00296
GPATCH4|54865 1.862e-07 0.00336
SEMA3G|56920 1.871e-07 0.00337
KIAA1383|54627 2.402e-07 0.00433

Figure S6.  Get High-res Image As an example, this figure shows the association of ARRB1|408 to 'DISTANT.METASTASIS'. P value = 2.2e-09 with ANOVA analysis.

Clinical variable #7: 'EXTRATHYROIDAL.EXTENSION'

120 genes related to 'EXTRATHYROIDAL.EXTENSION'.

Table S13.  Basic characteristics of clinical feature: 'EXTRATHYROIDAL.EXTENSION'

EXTRATHYROIDAL.EXTENSION Labels N
  MINIMAL (T3) 67
  MODERATE/ADVANCED (T4A) 5
  NONE 203
     
  Significant markers N = 120
List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

Table S14.  Get Full Table List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

ANOVA_P Q
PLRG1|5356 1.542e-09 2.78e-05
FOXJ1|2302 3.47e-09 6.25e-05
CYP26A1|1592 3.724e-09 6.71e-05
TSPYL5|85453 4.884e-09 8.8e-05
VEGFA|7422 5.924e-09 0.000107
FLJ42875|440556 8.633e-09 0.000156
PRDM16|63976 9.442e-09 0.00017
CETP|1071 1.197e-08 0.000216
FZD9|8326 1.584e-08 0.000285
BEGAIN|57596 2.065e-08 0.000372

Figure S7.  Get High-res Image As an example, this figure shows the association of PLRG1|5356 to 'EXTRATHYROIDAL.EXTENSION'. P value = 1.54e-09 with ANOVA analysis.

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

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

Table S15.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 145
  N1 16
  N1A 58
  N1B 42
  NX 28
     
  Significant markers N = 638
List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
KCNN4|3783 1.685e-12 3.04e-08
CREB5|9586 2.64e-11 4.76e-07
TACSTD2|4070 5.856e-11 1.06e-06
CLCNKA|1187 6.52e-11 1.18e-06
FN1|2335 1.694e-10 3.05e-06
SYT12|91683 1.793e-10 3.23e-06
ICAM1|3383 2.06e-10 3.71e-06
CCDC109B|55013 2.658e-10 4.79e-06
TMEM117|84216 2.907e-10 5.24e-06
PROS1|5627 2.99e-10 5.39e-06

Figure S8.  Get High-res Image As an example, this figure shows the association of KCNN4|3783 to 'LYMPH.NODE.METASTASIS'. P value = 1.68e-12 with ANOVA analysis.

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

3 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S17.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 229
  R1 18
  R2 1
  RX 20
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S18.  Get Full Table List of 3 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
CATSPER2P1|440278 1.217e-14 2.19e-10
MUC13|56667 8.566e-07 0.0154
TRIM72|493829 9.543e-07 0.0172

Figure S9.  Get High-res Image As an example, this figure shows the association of CATSPER2P1|440278 to 'COMPLETENESS.OF.RESECTION'. P value = 1.22e-14 with ANOVA analysis.

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

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

Table S19.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.8 (5.2)
  Significant markers N = 539
  pos. correlated 250
  neg. correlated 289
List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S20.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
PCDP1|200373 -0.4511 7.018e-13 1.26e-08
FAM60A|58516 0.4503 7.797e-13 1.41e-08
SPATS2L|26010 0.421 2.975e-11 5.36e-07
DIO2|1734 -0.4139 6.872e-11 1.24e-06
TMEM117|84216 0.4121 8.403e-11 1.51e-06
CBFB|865 0.4096 1.12e-10 2.02e-06
EMP2|2013 0.4078 1.381e-10 2.49e-06
SLC26A4|5172 -0.4055 1.774e-10 3.2e-06
SNX11|29916 -0.4053 1.83e-10 3.3e-06
CLCNKA|1187 -0.4046 1.972e-10 3.55e-06

Figure S10.  Get High-res Image As an example, this figure shows the association of PCDP1|200373 to 'NUMBER.OF.LYMPH.NODES'. P value = 7.02e-13 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'NEOPLASM.DISEASESTAGE'

133 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S21.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 163
  STAGE II 34
  STAGE III 62
  STAGE IVA 26
  STAGE IVC 3
     
  Significant markers N = 133
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S22.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
CYP26A1|1592 5.349e-12 9.64e-08
SEMA3G|56920 4.884e-10 8.8e-06
GOT2|2806 1.018e-09 1.84e-05
KIAA1383|54627 1.443e-09 2.6e-05
AIFM1|9131 3.508e-09 6.32e-05
ALDOA|226 5.267e-09 9.49e-05
GJA5|2702 6.471e-09 0.000117
CS|1431 1.012e-08 0.000182
MKKS|8195 1.211e-08 0.000218
C14ORF126|112487 2.166e-08 0.00039

Figure S11.  Get High-res Image As an example, this figure shows the association of CYP26A1|1592 to 'NEOPLASM.DISEASESTAGE'. P value = 5.35e-12 with ANOVA analysis.

Clinical variable #12: 'MULTIFOCALITY'

2 genes related to 'MULTIFOCALITY'.

Table S23.  Basic characteristics of clinical feature: 'MULTIFOCALITY'

MULTIFOCALITY Labels N
  MULTIFOCAL 143
  UNIFOCAL 137
     
  Significant markers N = 2
  Higher in UNIFOCAL 0
  Higher in MULTIFOCAL 2
List of 2 genes differentially expressed by 'MULTIFOCALITY'

Table S24.  Get Full Table List of 2 genes differentially expressed by 'MULTIFOCALITY'

T(pos if higher in 'UNIFOCAL') ttestP Q AUC
INMT|11185 -5.21 3.679e-07 0.00663 0.6661
ETS1|2113 -5.01 9.834e-07 0.0177 0.6585

Figure S12.  Get High-res Image As an example, this figure shows the association of INMT|11185 to 'MULTIFOCALITY'. P value = 3.68e-07 with T-test analysis.

Clinical variable #13: 'TUMOR.SIZE'

14 genes related to 'TUMOR.SIZE'.

Table S25.  Basic characteristics of clinical feature: 'TUMOR.SIZE'

TUMOR.SIZE Mean (SD) 2.65 (1.5)
  Significant markers N = 14
  pos. correlated 2
  neg. correlated 12
List of top 10 genes significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

Table S26.  Get Full Table List of top 10 genes significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

SpearmanCorr corrP Q
LRRC55|219527 -0.3519 1.084e-07 0.00195
ABCA6|23460 -0.3446 1.915e-07 0.00345
CLDN2|9075 -0.339 3.517e-07 0.00634
LSM12|124801 0.3325 5.338e-07 0.00962
PTGS1|5742 -0.3284 7.525e-07 0.0136
COL10A1|1300 -0.3288 7.738e-07 0.0139
PI16|221476 -0.3296 9.175e-07 0.0165
CD1E|913 -0.3264 1.415e-06 0.0255
AHCY|191 0.3205 1.42e-06 0.0256
DPT|1805 -0.3242 1.585e-06 0.0285

Figure S13.  Get High-res Image As an example, this figure shows the association of LRRC55|219527 to 'TUMOR.SIZE'. P value = 1.08e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

  • Expresson data file = THCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 289

  • Number of genes = 18025

  • 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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