Correlation between mRNAseq expression and clinical features
Thyroid Adenocarcinoma (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1JQ0Z8F
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1JQ0Z8F
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 271 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 ,  ZNF518B|85460 ,  DDIT4L|115265 ,  GPI|2821 ,  ...

  • 34 genes correlated to 'GENDER'.

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

  • 5329 genes correlated to 'HISTOLOGICAL.TYPE'.

    • FN1|2335 ,  FAM176A|84141 ,  KCNN4|3783 ,  GABRB2|2561 ,  SYT12|91683 ,  ...

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

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

  • 14 genes correlated to 'RADIATIONEXPOSURE'.

    • FAM138F|641702 ,  GSG1|83445 ,  P2RX2|22953 ,  OR9A4|130075 ,  CSNK1A1P|161635 ,  ...

  • 19 genes correlated to 'DISTANT.METASTASIS'.

    • ARRB1|408 ,  GJA5|2702 ,  RTN4RL1|146760 ,  GPATCH4|54865 ,  APOL3|80833 ,  ...

  • 93 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.

    • THNSL2|55258 ,  VEGFA|7422 ,  FOXJ1|2302 ,  PLRG1|5356 ,  TUBB1|81027 ,  ...

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

    • KCNN4|3783 ,  CREB5|9586 ,  CLCNKA|1187 ,  RASGRF1|5923 ,  TACSTD2|4070 ,  ...

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

    • CATSPER2P1|440278 ,  CXORF56|63932 ,  MUC13|56667 ,  TRIM72|493829

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

    • FAM60A|58516 ,  PCDP1|200373 ,  CBFB|865 ,  SPATS2L|26010 ,  SNX11|29916 ,  ...

  • 74 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • CYP26A1|1592 ,  KIAA1383|54627 ,  SEMA3G|56920 ,  AIFM1|9131 ,  ALDOA|226 ,  ...

  • 2 genes correlated to 'MULTIFOCALITY'.

    • INMT|11185 ,  ETS1|2113

  • 1 gene correlated to 'TUMOR.SIZE'.

    • LRRC55|219527

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=36 younger N=28
GENDER t test N=34 male N=13 female N=21
HISTOLOGICAL TYPE ANOVA test N=5329        
RADIATIONS RADIATION REGIMENINDICATION t test N=36 yes N=19 no N=17
RADIATIONEXPOSURE t test N=14 yes N=2 no N=12
DISTANT METASTASIS ANOVA test N=19        
EXTRATHYROIDAL EXTENSION ANOVA test N=93        
LYMPH NODE METASTASIS ANOVA test N=458        
COMPLETENESS OF RESECTION ANOVA test N=4        
NUMBER OF LYMPH NODES Spearman correlation test N=468 higher number.of.lymph.nodes N=230 lower number.of.lymph.nodes N=238
NEOPLASM DISEASESTAGE ANOVA test N=74        
MULTIFOCALITY t test N=2 unifocal N=0 multifocal N=2
TUMOR SIZE Spearman correlation test N=1 higher tumor.size N=0 lower tumor.size N=1
Clinical variable #1: 'AGE'

64 genes related to 'AGE'.

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

AGE Mean (SD) 46.69 (16)
  Significant markers N = 64
  pos. correlated 36
  neg. correlated 28
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 0.3809 8.707e-11 1.57e-06
DDX28|55794 0.362 8.185e-10 1.48e-05
ZNF518B|85460 -0.3472 4.277e-09 7.71e-05
DDIT4L|115265 0.3431 6.637e-09 0.00012
GPI|2821 0.3351 1.551e-08 0.000279
EPN3|55040 0.3298 2.687e-08 0.000484
IL20RA|53832 0.3266 3.934e-08 0.000709
ASB13|79754 0.3201 7.157e-08 0.00129
RAB3A|5864 0.3166 1.007e-07 0.00181
HADH|3033 0.3154 1.135e-07 0.00204

Figure S1.  Get High-res Image As an example, this figure shows the association of C12ORF52|84934 to 'AGE'. P value = 8.71e-11 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'GENDER'

34 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 200
  MALE 71
     
  Significant markers N = 34
  Higher in MALE 13
  Higher in FEMALE 21
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 84.95 1.392e-127 2.51e-123 1
ZFY|7544 78.78 7.518e-126 1.36e-121 1
RPS4Y1|6192 70.36 9.547e-125 1.72e-120 1
UTY|7404 79.58 2.222e-101 4e-97 1
USP9Y|8287 73.24 2.491e-97 4.49e-93 1
NLGN4Y|22829 55.83 1.138e-94 2.05e-90 1
KDM5D|8284 75.72 1.451e-88 2.62e-84 1
PRKY|5616 32.98 8.546e-88 1.54e-83 0.9983
CYORF15A|246126 62.1 1.059e-60 1.91e-56 1
XIST|7503 -37.44 1.503e-52 2.71e-48 0.9992

Figure S2.  Get High-res Image As an example, this figure shows the association of DDX3Y|8653 to 'GENDER'. P value = 1.39e-127 with T-test analysis.

Clinical variable #3: 'HISTOLOGICAL.TYPE'

5329 genes related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  OTHER 17
  THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL 159
  THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) 67
  THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) 28
     
  Significant markers N = 5329
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 7.798e-43 1.41e-38
FAM176A|84141 1.031e-40 1.86e-36
KCNN4|3783 5.044e-40 9.09e-36
GABRB2|2561 2.95e-37 5.32e-33
SYT12|91683 3.307e-37 5.96e-33
LDLR|3949 3.42e-37 6.16e-33
PTPRE|5791 6.751e-37 1.22e-32
SFTPB|6439 2.357e-36 4.25e-32
CREB5|9586 5.577e-36 1e-31
FLJ42709|441094 1.094e-35 1.97e-31

Figure S3.  Get High-res Image As an example, this figure shows the association of FN1|2335 to 'HISTOLOGICAL.TYPE'. P value = 7.8e-43 with ANOVA analysis.

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

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

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 12
  YES 259
     
  Significant markers N = 36
  Higher in YES 19
  Higher in NO 17
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 12.27 6.36e-15 1.14e-10 0.8665
C14ORF180|400258 10.2 5.806e-14 1.04e-09 0.8571
A2ML1|144568 9.36 3.925e-10 7.05e-06 0.8098
HPR|3250 8.76 9.629e-10 1.73e-05 0.9123
TAS2R43|259289 7.85 1.019e-09 1.83e-05 0.7595
HCFC1|3054 -10.57 4.406e-09 7.91e-05 0.9064
LOC440173|440173 7.61 1.554e-08 0.000279 0.8731
ARHGEF18|23370 -7.74 7.291e-08 0.00131 0.8012
TMEM218|219854 8.54 1.026e-07 0.00184 0.852
GINS1|9837 -6.69 1.351e-07 0.00242 0.7551

Figure S4.  Get High-res Image As an example, this figure shows the association of FLJ37543|285668 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 6.36e-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 225
  YES 10
     
  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
FAM138F|641702 -9.01 2.971e-14 5.3e-10 0.837
GSG1|83445 -8.44 6.433e-13 1.15e-08 0.8244
P2RX2|22953 -7.89 2.595e-11 4.63e-07 0.8826
OR9A4|130075 -8.06 2.634e-11 4.7e-07 0.8458
CSNK1A1P|161635 -7.47 7.498e-11 1.34e-06 0.8552
RPRML|388394 -7.4 3.959e-10 7.06e-06 0.8423
LOC100133050|100133050 -7.05 7.91e-08 0.00141 0.8102
TNNT3|7140 -9.77 8.83e-08 0.00157 0.8992
CYORF15A|246126 5.72 1.672e-07 0.00298 0.6188
DLX2|1746 -7.08 4.668e-07 0.00833 0.7468

Figure S5.  Get High-res Image As an example, this figure shows the association of FAM138F|641702 to 'RADIATIONEXPOSURE'. P value = 2.97e-14 with T-test analysis.

Clinical variable #6: 'DISTANT.METASTASIS'

19 genes related to 'DISTANT.METASTASIS'.

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

DISTANT.METASTASIS Labels N
  M0 123
  M1 4
  MX 143
     
  Significant markers N = 19
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 3.58e-09 6.45e-05
GJA5|2702 1.504e-08 0.000271
RTN4RL1|146760 1.524e-08 0.000275
GPATCH4|54865 3.266e-08 0.000589
APOL3|80833 1.65e-07 0.00297
SEMA3G|56920 2.272e-07 0.00409
PTPRR|5801 2.571e-07 0.00463
KIAA1383|54627 2.589e-07 0.00467
SNRNP40|9410 3.79e-07 0.00683
KYNU|8942 4.618e-07 0.00832

Figure S6.  Get High-res Image As an example, this figure shows the association of ARRB1|408 to 'DISTANT.METASTASIS'. P value = 3.58e-09 with ANOVA analysis.

Clinical variable #7: 'EXTRATHYROIDAL.EXTENSION'

93 genes related to 'EXTRATHYROIDAL.EXTENSION'.

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

EXTRATHYROIDAL.EXTENSION Labels N
  MINIMAL (T3) 62
  MODERATE/ADVANCED (T4A) 4
  NONE 191
     
  Significant markers N = 93
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
THNSL2|55258 1.123e-09 2.02e-05
VEGFA|7422 3.686e-09 6.64e-05
FOXJ1|2302 4.344e-09 7.83e-05
PLRG1|5356 4.626e-09 8.34e-05
TUBB1|81027 8.155e-09 0.000147
FZD9|8326 1.69e-08 0.000305
FLJ42875|440556 2.081e-08 0.000375
BEGAIN|57596 2.637e-08 0.000475
CETP|1071 2.899e-08 0.000522
CYP26A1|1592 3.389e-08 0.000611

Figure S7.  Get High-res Image As an example, this figure shows the association of THNSL2|55258 to 'EXTRATHYROIDAL.EXTENSION'. P value = 1.12e-09 with ANOVA analysis.

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

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

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

LYMPH.NODE.METASTASIS Labels N
  N0 134
  N1 14
  N1A 56
  N1B 40
  NX 27
     
  Significant markers N = 458
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 4.444e-11 8.01e-07
CREB5|9586 1.529e-10 2.76e-06
CLCNKA|1187 2.766e-10 4.98e-06
RASGRF1|5923 3.818e-10 6.88e-06
TACSTD2|4070 8.084e-10 1.46e-05
MEX3C|51320 1.044e-09 1.88e-05
FN1|2335 1.329e-09 2.4e-05
IL1RAP|3556 1.579e-09 2.84e-05
SYT12|91683 1.777e-09 3.2e-05
PELI1|57162 1.795e-09 3.23e-05

Figure S8.  Get High-res Image As an example, this figure shows the association of KCNN4|3783 to 'LYMPH.NODE.METASTASIS'. P value = 4.44e-11 with ANOVA analysis.

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

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

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

COMPLETENESS.OF.RESECTION Labels N
  R0 212
  R1 17
  R2 1
  RX 20
     
  Significant markers N = 4
List of 4 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S18.  Get Full Table List of 4 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
CATSPER2P1|440278 1.698e-14 3.06e-10
CXORF56|63932 1.034e-07 0.00186
MUC13|56667 5.443e-07 0.00981
TRIM72|493829 1.321e-06 0.0238

Figure S9.  Get High-res Image As an example, this figure shows the association of CATSPER2P1|440278 to 'COMPLETENESS.OF.RESECTION'. P value = 1.7e-14 with ANOVA analysis.

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

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

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

NUMBER.OF.LYMPH.NODES Mean (SD) 2.85 (5.3)
  Significant markers N = 468
  pos. correlated 230
  neg. correlated 238
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
FAM60A|58516 0.4736 2.615e-13 4.71e-09
PCDP1|200373 -0.4494 5.515e-12 9.94e-08
CBFB|865 0.4246 9.815e-11 1.77e-06
SPATS2L|26010 0.4189 1.852e-10 3.34e-06
SNX11|29916 -0.4176 2.13e-10 3.84e-06
MEX3C|51320 0.4078 6.119e-10 1.1e-05
CREB5|9586 0.4072 6.473e-10 1.17e-05
PELI1|57162 0.4072 6.53e-10 1.18e-05
TMEM99|147184 -0.4071 6.603e-10 1.19e-05
CLCNKA|1187 -0.4068 6.753e-10 1.22e-05

Figure S10.  Get High-res Image As an example, this figure shows the association of FAM60A|58516 to 'NUMBER.OF.LYMPH.NODES'. P value = 2.62e-13 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #11: 'NEOPLASM.DISEASESTAGE'

74 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 152
  STAGE II 33
  STAGE III 58
  STAGE IVA 24
  STAGE IVC 3
     
  Significant markers N = 74
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 1.942e-11 3.5e-07
KIAA1383|54627 1.259e-09 2.27e-05
SEMA3G|56920 1.578e-09 2.84e-05
AIFM1|9131 4.93e-09 8.88e-05
ALDOA|226 5.543e-09 9.99e-05
GOT2|2806 7.535e-09 0.000136
GJA5|2702 2.148e-08 0.000387
CS|1431 5.425e-08 0.000977
GPI|2821 7.655e-08 0.00138
ALPL|249 7.856e-08 0.00142

Figure S11.  Get High-res Image As an example, this figure shows the association of CYP26A1|1592 to 'NEOPLASM.DISEASESTAGE'. P value = 1.94e-11 with ANOVA analysis.

Clinical variable #12: 'MULTIFOCALITY'

2 genes related to 'MULTIFOCALITY'.

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

MULTIFOCALITY Labels N
  MULTIFOCAL 133
  UNIFOCAL 129
     
  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 -5.04 8.698e-07 0.0157 0.6663
ETS1|2113 -4.88 1.926e-06 0.0347 0.6609

Figure S12.  Get High-res Image As an example, this figure shows the association of INMT|11185 to 'MULTIFOCALITY'. P value = 8.7e-07 with T-test analysis.

Clinical variable #13: 'TUMOR.SIZE'

One gene related to 'TUMOR.SIZE'.

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

TUMOR.SIZE Mean (SD) 2.74 (1.5)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

Table S26.  Get Full Table List of one gene significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

SpearmanCorr corrP Q
LRRC55|219527 -0.3459 5.616e-07 0.0101

Figure S13.  Get High-res Image As an example, this figure shows the association of LRRC55|219527 to 'TUMOR.SIZE'. P value = 5.62e-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 = 271

  • 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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