Correlation between mRNAseq expression and clinical features
Colorectal Adenocarcinoma (Primary solid tumor)
23 September 2013  |  analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C16Q1VHM
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/C16Q1VHM
Overview
Introduction

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

Summary

Testing the association between 18068 genes and 12 clinical features across 310 samples, statistically thresholded by Q value < 0.05, 10 clinical features related to at least one genes.

  • 62 genes correlated to 'PRIMARY.SITE.OF.DISEASE'.

    • LOC644936|644936 ,  MTERF|7978 ,  ZNF141|7700 ,  ELAVL2|1993 ,  MAP7D2|256714 ,  ...

  • 14 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • PRH1|5554 ,  ZNF845|91664 ,  TDRD12|91646 ,  CDH22|64405 ,  TMEM185A|84548 ,  ...

  • 12 genes correlated to 'PATHOLOGY.T.STAGE'.

    • IGLON5|402665 ,  GADD45B|4616 ,  TRPC1|7220 ,  RAB6B|51560 ,  TCHH|7062 ,  ...

  • 106 genes correlated to 'PATHOLOGY.N.STAGE'.

    • TEAD3|7005 ,  RGL2|5863 ,  ZBTB20|26137 ,  COL11A2|1302 ,  HAP1|9001 ,  ...

  • 12 genes correlated to 'PATHOLOGY.M.STAGE'.

    • TDRD12|91646 ,  RB1|5925 ,  FAM171A1|221061 ,  ZNF558|148156 ,  TMEM185A|84548 ,  ...

  • 37 genes correlated to 'GENDER'.

    • XIST|7503 ,  ZFY|7544 ,  PRKY|5616 ,  RPS4Y1|6192 ,  KDM5D|8284 ,  ...

  • 228 genes correlated to 'HISTOLOGICAL.TYPE'.

    • USPL1|10208 ,  TOP1P1|7151 ,  LOC644936|644936 ,  AQP3|360 ,  PLAGL2|5326 ,  ...

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

    • HIST1H2AE|3012 ,  HMSD|284293 ,  ZNF813|126017 ,  BEST3|144453 ,  ZNF701|55762 ,  ...

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

    • LYG2|254773 ,  ZNHIT2|741

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

    • NIPAL4|348938 ,  SHC1|6464 ,  TEAD3|7005 ,  TACSTD2|4070 ,  RGL2|5863 ,  ...

  • No genes correlated to 'Time to Death', and 'AGE'.

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=0        
PRIMARY SITE OF DISEASE t test N=62 rectum N=47 colon N=15
NEOPLASM DISEASESTAGE ANOVA test N=14        
PATHOLOGY T STAGE Spearman correlation test N=12 higher stage N=12 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test N=106 higher stage N=78 lower stage N=28
PATHOLOGY M STAGE ANOVA test N=12        
GENDER t test N=37 male N=13 female N=24
HISTOLOGICAL TYPE ANOVA test N=228        
RADIATIONS RADIATION REGIMENINDICATION t test N=8 yes N=3 no N=5
COMPLETENESS OF RESECTION ANOVA test N=2        
NUMBER OF LYMPH NODES Spearman correlation test N=37 higher number.of.lymph.nodes N=31 lower number.of.lymph.nodes N=6
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) 0.1-140.4 (median=13)
  censored N = 243
  death N = 52
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 64.63 (13)
  Significant markers N = 0
Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

62 genes related to 'PRIMARY.SITE.OF.DISEASE'.

Table S3.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  COLON 226
  RECTUM 82
     
  Significant markers N = 62
  Higher in RECTUM 47
  Higher in COLON 15
List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S4.  Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

T(pos if higher in 'RECTUM') ttestP Q AUC
LOC644936|644936 -7.4 7.516e-12 1.36e-07 0.743
MTERF|7978 7.04 1.317e-11 2.38e-07 0.6745
ZNF141|7700 6.93 2.605e-11 4.71e-07 0.6949
ELAVL2|1993 6.99 4.52e-11 8.17e-07 0.7215
MAP7D2|256714 6.84 7.472e-11 1.35e-06 0.6903
ZNF595|152687 6.66 2.251e-10 4.07e-06 0.718
LOC647979|647979 6.15 5.527e-09 9.98e-05 0.6909
SHROOM4|57477 5.9 1.181e-08 0.000213 0.6651
C19ORF46|163183 5.86 1.35e-08 0.000244 0.6253
R3HDML|140902 5.95 1.356e-08 0.000245 0.7002

Figure S1.  Get High-res Image As an example, this figure shows the association of LOC644936|644936 to 'PRIMARY.SITE.OF.DISEASE'. P value = 7.52e-12 with T-test analysis.

Clinical variable #4: 'NEOPLASM.DISEASESTAGE'

14 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S5.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 45
  STAGE IA 1
  STAGE II 20
  STAGE IIA 85
  STAGE IIB 5
  STAGE IIC 3
  STAGE III 11
  STAGE IIIA 12
  STAGE IIIB 46
  STAGE IIIC 26
  STAGE IV 22
  STAGE IVA 21
  STAGE IVB 1
     
  Significant markers N = 14
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
PRH1|5554 7.521e-10 1.36e-05
ZNF845|91664 3.199e-09 5.78e-05
TDRD12|91646 9.143e-09 0.000165
CDH22|64405 5.212e-08 0.000942
TMEM185A|84548 3.046e-07 0.0055
HAP1|9001 3.176e-07 0.00574
FAM171A1|221061 4.394e-07 0.00794
USP26|83844 4.834e-07 0.00873
RB1|5925 9.318e-07 0.0168
ZNF558|148156 1.157e-06 0.0209

Figure S2.  Get High-res Image As an example, this figure shows the association of PRH1|5554 to 'NEOPLASM.DISEASESTAGE'. P value = 7.52e-10 with ANOVA analysis.

Clinical variable #5: 'PATHOLOGY.T.STAGE'

12 genes related to 'PATHOLOGY.T.STAGE'.

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.91 (0.64)
  N
  0 1
  1 8
  2 48
  3 212
  4 39
     
  Significant markers N = 12
  pos. correlated 12
  neg. correlated 0
List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
IGLON5|402665 0.3115 3.396e-08 0.000614
GADD45B|4616 0.2897 2.278e-07 0.00412
TRPC1|7220 0.2803 5.72e-07 0.0103
RAB6B|51560 0.2786 6.778e-07 0.0122
TCHH|7062 0.2806 7.193e-07 0.013
MLLT11|10962 0.2777 7.329e-07 0.0132
FSTL3|10272 0.2768 8.041e-07 0.0145
VEGFC|7424 0.269 1.672e-06 0.0302
DFNA5|1687 0.2687 1.716e-06 0.031
PCDHB6|56130 0.2697 1.892e-06 0.0342

Figure S3.  Get High-res Image As an example, this figure shows the association of IGLON5|402665 to 'PATHOLOGY.T.STAGE'. P value = 3.4e-08 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.N.STAGE'

106 genes related to 'PATHOLOGY.N.STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.62 (0.76)
  N
  0 170
  1 83
  2 53
     
  Significant markers N = 106
  pos. correlated 78
  neg. correlated 28
List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
TEAD3|7005 0.3469 4.426e-10 8e-06
RGL2|5863 0.3381 1.287e-09 2.33e-05
ZBTB20|26137 0.3309 2.975e-09 5.37e-05
COL11A2|1302 0.3219 9.265e-09 0.000167
HAP1|9001 0.3225 1.298e-08 0.000234
MAPKAPK3|7867 -0.3138 2.038e-08 0.000368
NARS|4677 -0.3095 3.249e-08 0.000587
HIST2H2BF|440689 0.3073 4.106e-08 0.000742
TCHH|7062 0.3092 4.579e-08 0.000827
UNG|7374 -0.3061 4.626e-08 0.000835

Figure S4.  Get High-res Image As an example, this figure shows the association of TEAD3|7005 to 'PATHOLOGY.N.STAGE'. P value = 4.43e-10 with Spearman correlation analysis.

Clinical variable #7: 'PATHOLOGY.M.STAGE'

12 genes related to 'PATHOLOGY.M.STAGE'.

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 213
  M1 32
  M1A 7
  M1B 1
  MX 51
     
  Significant markers N = 12
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
TDRD12|91646 8.313e-11 1.5e-06
RB1|5925 2.749e-10 4.97e-06
FAM171A1|221061 4.711e-10 8.51e-06
ZNF558|148156 4.181e-09 7.55e-05
TMEM185A|84548 4.851e-09 8.76e-05
ZNF675|171392 5.428e-09 9.81e-05
ZNF845|91664 8.688e-09 0.000157
CCDC122|160857 9.879e-08 0.00178
CDH12|1010 4.617e-07 0.00834
C13ORF31|144811 4.7e-07 0.00849

Figure S5.  Get High-res Image As an example, this figure shows the association of TDRD12|91646 to 'PATHOLOGY.M.STAGE'. P value = 8.31e-11 with ANOVA analysis.

Clinical variable #8: 'GENDER'

37 genes related to 'GENDER'.

Table S13.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 138
  MALE 172
     
  Significant markers N = 37
  Higher in MALE 13
  Higher in FEMALE 24
List of top 10 genes differentially expressed by 'GENDER'

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

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503 -47.96 3.674e-136 6.64e-132 0.9992
ZFY|7544 51.08 1.219e-124 2.2e-120 0.9992
PRKY|5616 34.82 1.115e-102 2.01e-98 0.9964
RPS4Y1|6192 41.57 1.158e-99 2.09e-95 0.9997
KDM5D|8284 52.68 9.619e-79 1.74e-74 0.9998
DDX3Y|8653 51.23 2.059e-76 3.72e-72 0.9999
NLGN4Y|22829 37.5 1.748e-64 3.16e-60 0.9993
TSIX|9383 -23.73 2.839e-62 5.13e-58 0.9933
CYORF15B|84663 35.91 3.139e-61 5.67e-57 0.9998
EIF1AY|9086 39.29 2.883e-52 5.21e-48 0.9996

Figure S6.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 3.67e-136 with T-test analysis.

Clinical variable #9: 'HISTOLOGICAL.TYPE'

228 genes related to 'HISTOLOGICAL.TYPE'.

Table S15.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 196
  COLON MUCINOUS ADENOCARCINOMA 30
  RECTAL ADENOCARCINOMA 78
  RECTAL MUCINOUS ADENOCARCINOMA 4
     
  Significant markers N = 228
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
USPL1|10208 2.774e-12 5.01e-08
TOP1P1|7151 2.261e-11 4.09e-07
LOC644936|644936 3.714e-11 6.71e-07
AQP3|360 5.352e-11 9.67e-07
PLAGL2|5326 5.888e-11 1.06e-06
ASCL2|430 7.705e-11 1.39e-06
CSE1L|1434 7.761e-11 1.4e-06
DDX27|55661 2.32e-10 4.19e-06
RPL21|6144 2.964e-10 5.35e-06
MAPRE2|10982 4.175e-10 7.54e-06

Figure S7.  Get High-res Image As an example, this figure shows the association of USPL1|10208 to 'HISTOLOGICAL.TYPE'. P value = 2.77e-12 with ANOVA analysis.

Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S17.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 8
  YES 302
     
  Significant markers N = 8
  Higher in YES 3
  Higher in NO 5
List of 8 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S18.  Get Full Table List of 8 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
HIST1H2AE|3012 -12.59 2.444e-11 4.37e-07 0.8498
HMSD|284293 11.18 8.387e-11 1.5e-06 0.7992
ZNF813|126017 -9.86 5.054e-10 9.05e-06 0.7616
BEST3|144453 10.92 3.532e-08 0.000632 0.848
ZNF701|55762 -8.51 7.92e-08 0.00142 0.7815
MMRN1|22915 -8.56 8.414e-07 0.0151 0.8154
MAEA|10296 8.81 1.612e-06 0.0288 0.8456
GAPDHS|26330 -9.21 1.672e-06 0.0299 0.8606

Figure S8.  Get High-res Image As an example, this figure shows the association of HIST1H2AE|3012 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.44e-11 with T-test analysis.

Clinical variable #11: 'COMPLETENESS.OF.RESECTION'

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

Table S19.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 190
  R1 2
  R2 3
  RX 28
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S20.  Get Full Table List of 2 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
LYG2|254773 4.168e-12 7.53e-08
ZNHIT2|741 1.642e-07 0.00297

Figure S9.  Get High-res Image As an example, this figure shows the association of LYG2|254773 to 'COMPLETENESS.OF.RESECTION'. P value = 4.17e-12 with ANOVA analysis.

Clinical variable #12: 'NUMBER.OF.LYMPH.NODES'

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

Table S21.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.3 (5)
  Significant markers N = 37
  pos. correlated 31
  neg. correlated 6
List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

Table S22.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
NIPAL4|348938 0.3358 1.135e-08 0.000205
SHC1|6464 0.3229 3.839e-08 0.000694
TEAD3|7005 0.3223 4.081e-08 0.000737
TACSTD2|4070 0.321 4.686e-08 0.000847
RGL2|5863 0.3163 7.465e-08 0.00135
AMIGO2|347902 0.3125 1.09e-07 0.00197
HIST2H4A|8370 0.3101 1.372e-07 0.00248
TCHH|7062 0.3129 1.44e-07 0.0026
HIST2H2BF|440689 0.3051 2.224e-07 0.00402
C5ORF23|79614 0.3062 2.234e-07 0.00403

Figure S10.  Get High-res Image As an example, this figure shows the association of NIPAL4|348938 to 'NUMBER.OF.LYMPH.NODES'. P value = 1.14e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

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

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

  • Number of patients = 310

  • Number of genes = 18068

  • Number of clinical features = 12

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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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)
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