Correlation between mRNAseq expression and clinical features
Thyroid Adenocarcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1MK69W5
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Thyroid Adenocarcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1MK69W5
Overview
Introduction

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

Summary

Testing the association between 18001 genes and 14 clinical features across 397 samples, statistically thresholded by Q value < 0.05, 12 clinical features related to at least one genes.

  • 135 genes correlated to 'AGE'.

    • ZNF518B|85460 ,  C12ORF52|84934 ,  IL20RA|53832 ,  STL|7955 ,  MSL3L2|151507 ,  ...

  • 39 genes correlated to 'GENDER'.

    • RPS4Y1|6192 ,  DDX3Y|8653 ,  ZFY|7544 ,  UTY|7404 ,  NLGN4Y|22829 ,  ...

  • 4479 genes correlated to 'HISTOLOGICAL.TYPE'.

    • FN1|2335 ,  ITGA3|3675 ,  KCNN4|3783 ,  ANXA2P2|304 ,  MUC1|4582 ,  ...

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

    • C14ORF180|400258 ,  FLJ37543|285668 ,  TAS2R43|259289 ,  ADIPOQ|9370 ,  HPR|3250 ,  ...

  • 8 genes correlated to 'RADIATIONEXPOSURE'.

    • CRNN|49860 ,  C13ORF30|144809 ,  P2RX2|22953 ,  CSNK1A1P|161635 ,  CYP2C9|1559 ,  ...

  • 9 genes correlated to 'DISTANT.METASTASIS'.

    • RTN4RL1|146760 ,  CYP21A2|1589 ,  RNF207|388591 ,  KYNU|8942 ,  HSPA6|3310 ,  ...

  • 718 genes correlated to 'EXTRATHYROIDAL.EXTENSION'.

    • ASAH2|56624 ,  CYP26A1|1592 ,  COL11A1|1301 ,  FOXJ1|2302 ,  FAM69C|125704 ,  ...

  • 1245 genes correlated to 'LYMPH.NODE.METASTASIS'.

    • CREB5|9586 ,  CTSC|1075 ,  KCNN4|3783 ,  FN1|2335 ,  ICAM1|3383 ,  ...

  • 1 gene correlated to 'COMPLETENESS.OF.RESECTION'.

    • CATSPER2P1|440278

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

    • CBFB|865 ,  PELI1|57162 ,  ZNF346|23567 ,  FAM60A|58516 ,  TAGLN2|8407 ,  ...

  • 235 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • ASAH2|56624 ,  YKT6|10652 ,  CYP26A1|1592 ,  FAM169A|26049 ,  ZNF518B|85460 ,  ...

  • 5 genes correlated to 'TUMOR.SIZE'.

    • LOC151162|151162 ,  CLDN2|9075 ,  ZC3H10|84872 ,  FOXI2|399823 ,  C3ORF32|51066

  • No genes correlated to 'Time to Death', 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
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=135 older N=59 younger N=76
GENDER t test N=39 male N=16 female N=23
HISTOLOGICAL TYPE ANOVA test N=4479        
RADIATIONS RADIATION REGIMENINDICATION t test N=26 yes N=18 no N=8
RADIATIONEXPOSURE t test N=8 yes N=3 no N=5
DISTANT METASTASIS ANOVA test N=9        
EXTRATHYROIDAL EXTENSION ANOVA test N=718        
LYMPH NODE METASTASIS ANOVA test N=1245        
COMPLETENESS OF RESECTION ANOVA test N=1        
NUMBER OF LYMPH NODES Spearman correlation test N=755 higher number.of.lymph.nodes N=397 lower number.of.lymph.nodes N=358
NEOPLASM DISEASESTAGE ANOVA test N=235        
MULTIFOCALITY t test   N=0        
TUMOR SIZE Spearman correlation test N=5 higher tumor.size N=0 lower tumor.size N=5
Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0-147.4 (median=9.3)
  censored N = 382
  death N = 10
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

135 genes related to 'AGE'.

Table S2.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 46.48 (16)
  Significant markers N = 135
  pos. correlated 59
  neg. correlated 76
List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
ZNF518B|85460 -0.3495 7.575e-13 1.36e-08
C12ORF52|84934 0.3236 3.945e-11 7.1e-07
IL20RA|53832 0.3237 4.358e-11 7.84e-07
STL|7955 -0.3217 5.242e-11 9.44e-07
MSL3L2|151507 -0.3183 8.513e-11 1.53e-06
RANBP17|64901 -0.3191 8.941e-11 1.61e-06
ASB13|79754 0.3169 1.039e-10 1.87e-06
HCG11|493812 -0.3095 2.907e-10 5.23e-06
DDIT4L|115265 0.3043 6.23e-10 1.12e-05
MST1P9|11223 -0.3024 7.679e-10 1.38e-05

Figure S1.  Get High-res Image As an example, this figure shows the association of ZNF518B|85460 to 'AGE'. P value = 7.58e-13 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

39 genes related to 'GENDER'.

Table S4.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 298
  MALE 99
     
  Significant markers N = 39
  Higher in MALE 16
  Higher in FEMALE 23
List of top 10 genes differentially expressed by 'GENDER'

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

T(pos if higher in 'MALE') ttestP Q AUC
RPS4Y1|6192 80.5 1.477e-163 2.66e-159 1
DDX3Y|8653 84.93 7.108e-155 1.28e-150 1
ZFY|7544 80.95 2.326e-154 4.19e-150 1
UTY|7404 79.55 4.082e-127 7.35e-123 1
NLGN4Y|22829 59.4 4.15e-125 7.47e-121 1
KDM5D|8284 75.46 3.685e-118 6.63e-114 1
USP9Y|8287 64.62 3.545e-109 6.38e-105 0.9998
PRKY|5616 36.28 5.916e-104 1.06e-99 0.9919
XIST|7503 -41.37 1.191e-67 2.14e-63 0.9924
CYORF15A|246126 51.97 6.42e-60 1.16e-55 1

Figure S2.  Get High-res Image As an example, this figure shows the association of RPS4Y1|6192 to 'GENDER'. P value = 1.48e-163 with T-test analysis.

Clinical variable #4: 'HISTOLOGICAL.TYPE'

4479 genes related to 'HISTOLOGICAL.TYPE'.

Table S6.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  OTHER SPECIFY 6
  THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL 273
  THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED) 84
  THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES) 34
     
  Significant markers N = 4479
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
FN1|2335 2.45e-37 4.41e-33
ITGA3|3675 4.107e-37 7.39e-33
KCNN4|3783 2.642e-35 4.76e-31
ANXA2P2|304 4.889e-35 8.8e-31
MUC1|4582 1.3e-34 2.34e-30
SERPINA1|5265 3.871e-34 6.97e-30
CEACAM6|4680 4.317e-34 7.77e-30
UNC5CL|222643 4.499e-34 8.1e-30
SFTPB|6439 5.836e-34 1.05e-29
B3GNT3|10331 6.228e-34 1.12e-29

Figure S3.  Get High-res Image As an example, this figure shows the association of FN1|2335 to 'HISTOLOGICAL.TYPE'. P value = 2.45e-37 with ANOVA analysis.

Clinical variable #5: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S8.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 13
  YES 384
     
  Significant markers N = 26
  Higher in YES 18
  Higher in NO 8
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
C14ORF180|400258 12.3 3.234e-14 5.81e-10 0.8773
FLJ37543|285668 14.08 1.251e-13 2.25e-09 0.882
TAS2R43|259289 9.53 1.441e-11 2.59e-07 0.7799
ADIPOQ|9370 10.64 2.466e-11 4.43e-07 0.9127
HPR|3250 10.29 9.118e-10 1.64e-05 0.9191
LOC440173|440173 8.79 1.181e-08 0.000212 0.8796
ENPP3|5169 8.93 2.687e-08 0.000482 0.8598
CXORF48|54967 8.5 2.779e-07 0.00499 0.8294
C6ORF203|51250 8.53 3.081e-07 0.00553 0.8746
HCFC1|3054 -8.68 3.449e-07 0.00619 0.8992

Figure S4.  Get High-res Image As an example, this figure shows the association of C14ORF180|400258 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 3.23e-14 with T-test analysis.

Clinical variable #6: 'RADIATIONEXPOSURE'

8 genes related to 'RADIATIONEXPOSURE'.

Table S10.  Basic characteristics of clinical feature: 'RADIATIONEXPOSURE'

RADIATIONEXPOSURE Labels N
  NO 339
  YES 16
     
  Significant markers N = 8
  Higher in YES 3
  Higher in NO 5
List of 8 genes differentially expressed by 'RADIATIONEXPOSURE'

Table S11.  Get Full Table List of 8 genes differentially expressed by 'RADIATIONEXPOSURE'

T(pos if higher in 'YES') ttestP Q AUC
CRNN|49860 -12.06 8.795e-21 1.58e-16 0.9248
C13ORF30|144809 -11.07 2.057e-19 3.7e-15 0.8667
P2RX2|22953 -8.68 6.791e-14 1.22e-09 0.8944
CSNK1A1P|161635 -7.54 4.53e-11 8.15e-07 0.8143
CYP2C9|1559 -7.27 6.856e-10 1.23e-05 0.7223
CYORF15A|246126 6.65 9.76e-10 1.75e-05 0.6106
EIF1AY|9086 5.27 7.609e-07 0.0137 0.7668
TTTY15|64595 5.07 2.371e-06 0.0426 0.6863

Figure S5.  Get High-res Image As an example, this figure shows the association of CRNN|49860 to 'RADIATIONEXPOSURE'. P value = 8.8e-21 with T-test analysis.

Clinical variable #7: 'DISTANT.METASTASIS'

9 genes related to 'DISTANT.METASTASIS'.

Table S12.  Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS Labels N
  M0 218
  M1 7
  MX 171
     
  Significant markers N = 9
List of 9 genes differentially expressed by 'DISTANT.METASTASIS'

Table S13.  Get Full Table List of 9 genes differentially expressed by 'DISTANT.METASTASIS'

ANOVA_P Q
RTN4RL1|146760 2.066e-07 0.00372
CYP21A2|1589 2.271e-07 0.00409
RNF207|388591 2.7e-07 0.00486
KYNU|8942 6.759e-07 0.0122
HSPA6|3310 1.225e-06 0.022
APOL3|80833 2.073e-06 0.0373
SEMA3G|56920 2.159e-06 0.0389
GJA5|2702 2.368e-06 0.0426
SNORA8|654320 2.751e-06 0.0495

Figure S6.  Get High-res Image As an example, this figure shows the association of RTN4RL1|146760 to 'DISTANT.METASTASIS'. P value = 2.07e-07 with ANOVA analysis.

Clinical variable #8: 'EXTRATHYROIDAL.EXTENSION'

718 genes related to 'EXTRATHYROIDAL.EXTENSION'.

Table S14.  Basic characteristics of clinical feature: 'EXTRATHYROIDAL.EXTENSION'

EXTRATHYROIDAL.EXTENSION Labels N
  MINIMAL (T3) 104
  MODERATE/ADVANCED (T4A) 12
  NONE 263
  VERY ADVANCED (T4B) 1
     
  Significant markers N = 718
List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'EXTRATHYROIDAL.EXTENSION'

ANOVA_P Q
ASAH2|56624 4.425e-15 7.97e-11
CYP26A1|1592 2.715e-13 4.89e-09
COL11A1|1301 3.216e-13 5.79e-09
FOXJ1|2302 3.668e-13 6.6e-09
FAM69C|125704 4.044e-13 7.28e-09
SLC25A42|284439 4.558e-13 8.2e-09
ZNF540|163255 8.342e-13 1.5e-08
COL1A1|1277 1.336e-12 2.4e-08
FAM169A|26049 1.372e-12 2.47e-08
COL3A1|1281 1.482e-12 2.67e-08

Figure S7.  Get High-res Image As an example, this figure shows the association of ASAH2|56624 to 'EXTRATHYROIDAL.EXTENSION'. P value = 4.42e-15 with ANOVA analysis.

Clinical variable #9: 'LYMPH.NODE.METASTASIS'

1245 genes related to 'LYMPH.NODE.METASTASIS'.

Table S16.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 188
  N1 42
  N1A 75
  N1B 55
  NX 37
     
  Significant markers N = 1245
List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
CREB5|9586 4.234e-15 7.62e-11
CTSC|1075 1.718e-14 3.09e-10
KCNN4|3783 3.209e-14 5.78e-10
FN1|2335 1.524e-13 2.74e-09
ICAM1|3383 1.552e-13 2.79e-09
WFS1|7466 2.418e-13 4.35e-09
CLCNKA|1187 2.556e-13 4.6e-09
SFTPB|6439 3.081e-13 5.54e-09
CD58|965 3.643e-13 6.55e-09
TPM3|7170 5.221e-13 9.39e-09

Figure S8.  Get High-res Image As an example, this figure shows the association of CREB5|9586 to 'LYMPH.NODE.METASTASIS'. P value = 4.23e-15 with ANOVA analysis.

Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

One gene related to 'COMPLETENESS.OF.RESECTION'.

Table S18.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 313
  R1 32
  R2 2
  RX 25
     
  Significant markers N = 1
List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S19.  Get Full Table List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
CATSPER2P1|440278 4.446e-09 8e-05

Figure S9.  Get High-res Image As an example, this figure shows the association of CATSPER2P1|440278 to 'COMPLETENESS.OF.RESECTION'. P value = 4.45e-09 with ANOVA analysis.

Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

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

Table S20.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 3.35 (6)
  Significant markers N = 755
  pos. correlated 397
  neg. correlated 358
List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S21.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
CBFB|865 0.4084 1.316e-13 2.37e-09
PELI1|57162 0.3956 8.529e-13 1.54e-08
ZNF346|23567 -0.3952 9.041e-13 1.63e-08
FAM60A|58516 0.39 1.908e-12 3.43e-08
TAGLN2|8407 0.3893 2.095e-12 3.77e-08
LOC100131193|100131193 -0.3857 3.479e-12 6.26e-08
CREB5|9586 0.3843 4.238e-12 7.63e-08
S100A10|6281 0.3837 4.595e-12 8.27e-08
CCDC109B|55013 0.3828 5.164e-12 9.29e-08
MLEC|9761 -0.3803 7.292e-12 1.31e-07

Figure S10.  Get High-res Image As an example, this figure shows the association of CBFB|865 to 'NUMBER.OF.LYMPH.NODES'. P value = 1.32e-13 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #12: 'NEOPLASM.DISEASESTAGE'

235 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S22.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 225
  STAGE II 45
  STAGE III 86
  STAGE IV 1
  STAGE IVA 32
  STAGE IVC 5
     
  Significant markers N = 235
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S23.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
ASAH2|56624 7.95e-14 1.43e-09
YKT6|10652 1.471e-13 2.65e-09
CYP26A1|1592 6.789e-13 1.22e-08
FAM169A|26049 2.482e-10 4.47e-06
ZNF518B|85460 3.224e-10 5.8e-06
SHC1|6464 3.948e-10 7.11e-06
LOC145820|145820 4.372e-10 7.87e-06
MKKS|8195 4.556e-10 8.2e-06
HARS2|23438 6.727e-10 1.21e-05
PLOD3|8985 1.24e-09 2.23e-05

Figure S11.  Get High-res Image As an example, this figure shows the association of ASAH2|56624 to 'NEOPLASM.DISEASESTAGE'. P value = 7.95e-14 with ANOVA analysis.

Clinical variable #13: 'MULTIFOCALITY'

No gene related to 'MULTIFOCALITY'.

Table S24.  Basic characteristics of clinical feature: 'MULTIFOCALITY'

MULTIFOCALITY Labels N
  MULTIFOCAL 173
  UNIFOCAL 215
     
  Significant markers N = 0
Clinical variable #14: 'TUMOR.SIZE'

5 genes related to 'TUMOR.SIZE'.

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

TUMOR.SIZE Mean (SD) 2.91 (1.6)
  Significant markers N = 5
  pos. correlated 0
  neg. correlated 5
List of 5 genes significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

Table S26.  Get Full Table List of 5 genes significantly correlated to 'TUMOR.SIZE' by Spearman correlation test

SpearmanCorr corrP Q
LOC151162|151162 -0.2782 5.672e-07 0.0102
CLDN2|9075 -0.2771 7.161e-07 0.0129
ZC3H10|84872 -0.2755 7.416e-07 0.0133
FOXI2|399823 -0.2731 1.052e-06 0.0189
C3ORF32|51066 -0.266 2.448e-06 0.0441

Figure S12.  Get High-res Image As an example, this figure shows the association of LOC151162|151162 to 'TUMOR.SIZE'. P value = 5.67e-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 = 397

  • Number of genes = 18001

  • Number of clinical features = 14

Survival analysis

For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels

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] Andersen and Gill, Cox's regression model for counting processes, a large sample study, Annals of Statistics 10(4):1100-1120 (1982)
[2] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[3] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[5] 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)
Copyright © 2013 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle