Correlation between mRNAseq expression and clinical features
Skin Cutaneous Melanoma (Metastatic)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C17W6B0M
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features.

Summary

Testing the association between 18086 genes and 14 clinical features across 285 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 645 genes correlated to 'Time from Specimen Diagnosis to Death'.

    • SAMSN1|64092 ,  CXCL10|3627 ,  EAF2|55840 ,  GBP5|115362 ,  LAG3|3902 ,  ...

  • 18 genes correlated to 'AGE'.

    • ACOX2|8309 ,  CMBL|134147 ,  FAM84B|157638 ,  MAOB|4129 ,  MGST2|4258 ,  ...

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

    • C7|730 ,  SHISA3|152573 ,  RBP5|83758 ,  FOXF1|2294 ,  TMEM156|80008 ,  ...

  • 2 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • RAI14|26064 ,  SEMA3E|9723

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

    • INHA|3623 ,  TNFSF13B|10673 ,  GBP4|115361 ,  LOXL4|84171 ,  ANKRD22|118932 ,  ...

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

    • C12ORF62|84987 ,  PTPRG|5793 ,  IL17RD|54756 ,  MAML3|55534 ,  TMEM208|29100 ,  ...

  • 73 genes correlated to 'BRESLOW.THICKNESS'.

    • TNFSF13B|10673 ,  GBP4|115361 ,  SLC7A8|23428 ,  ATP6V0A1|535 ,  FGL2|10875 ,  ...

  • 5 genes correlated to 'GENDER'.

    • CYORF15A|246126 ,  HDHD1A|8226 ,  NCRNA00183|554203 ,  CYORF15B|84663 ,  CA5BP|340591

  • No genes correlated to 'Time to Death', 'PATHOLOGY.M.STAGE', 'MELANOMA.ULCERATION', 'MELANOMA.PRIMARY.KNOWN', 'RACE', and 'ETHNICITY'.

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 P value < 0.05 and Q value < 0.3.

Clinical feature Statistical test Significant genes Associated with                 Associated with
Time from Specimen Diagnosis to Death Cox regression test N=645 shorter survival N=30 longer survival N=615
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=18 older N=3 younger N=15
PRIMARY SITE OF DISEASE Kruskal-Wallis test N=261        
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=2        
PATHOLOGY T STAGE Spearman correlation test N=10 higher stage N=1 lower stage N=9
PATHOLOGY N STAGE Spearman correlation test N=7 higher stage N=2 lower stage N=5
PATHOLOGY M STAGE Kruskal-Wallis test   N=0        
MELANOMA ULCERATION Wilcoxon test   N=0        
MELANOMA PRIMARY KNOWN Wilcoxon test   N=0        
BRESLOW THICKNESS Spearman correlation test N=73 higher breslow.thickness N=19 lower breslow.thickness N=54
GENDER Wilcoxon test N=5 male N=5 female N=0
RACE Kruskal-Wallis test   N=0        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'Time from Specimen Diagnosis to Death'

645 genes related to 'Time from Specimen Diagnosis to Death'.

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

Time from Specimen Diagnosis to Death Duration (Months) 0-124.3 (median=14.1)
  censored N = 138
  death N = 134
     
  Significant markers N = 645
  associated with shorter survival 30
  associated with longer survival 615
List of top 10 genes differentially expressed by 'Time from Specimen Diagnosis to Death'

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time from Specimen Diagnosis to Death' by Cox regression test

HazardRatio Wald_P Q C_index
SAMSN1|64092 0.76 4.238e-12 7.7e-08 0.321
CXCL10|3627 0.8 1.259e-11 2.3e-07 0.313
EAF2|55840 0.65 1.302e-11 2.4e-07 0.322
GBP5|115362 0.81 2.59e-11 4.7e-07 0.324
LAG3|3902 0.79 2.944e-11 5.3e-07 0.325
CD38|952 0.81 3.099e-11 5.6e-07 0.324
GCH1|2643 0.67 4.601e-11 8.3e-07 0.321
CD80|941 0.75 5.248e-11 9.5e-07 0.321
GBP2|2634 0.72 7.245e-11 1.3e-06 0.328
B2M|567 0.64 1.097e-10 2e-06 0.329
Clinical variable #2: 'Time to Death'

No gene related to 'Time to Death'.

Table S3.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0.2-357.4 (median=47.5)
  censored N = 144
  death N = 135
     
  Significant markers N = 0
Clinical variable #3: 'AGE'

18 genes related to 'AGE'.

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

AGE Mean (SD) 55.74 (15)
  Significant markers N = 18
  pos. correlated 3
  neg. correlated 15
List of top 10 genes differentially expressed by 'AGE'

Table S5.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
ACOX2|8309 -0.3363 7.849e-09 0.000142
CMBL|134147 -0.2956 4.719e-07 0.00853
FAM84B|157638 -0.2947 5.148e-07 0.00931
MAOB|4129 -0.2938 5.567e-07 0.0101
MGST2|4258 -0.2802 1.91e-06 0.0345
PRDX6|9588 -0.2778 2.354e-06 0.0426
PPP1R1B|84152 -0.2865 3.637e-06 0.0658
PHKA1|5255 -0.2694 4.817e-06 0.0871
CLEC1A|51267 -0.2656 6.596e-06 0.119
MCHR1|2847 -0.2673 6.982e-06 0.126
Clinical variable #4: 'PRIMARY.SITE.OF.DISEASE'

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

Table S6.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  DISTANT METASTASIS 39
  PRIMARY TUMOR 4
  REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE 61
  REGIONAL LYMPH NODE 180
     
  Significant markers N = 261
List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

ANOVA_P Q
C7|730 3.75e-11 6.78e-07
SHISA3|152573 1.093e-10 1.98e-06
RBP5|83758 1.305e-10 2.36e-06
FOXF1|2294 1.389e-10 2.51e-06
TMEM156|80008 1.746e-09 3.16e-05
C13ORF30|144809 2.098e-09 3.79e-05
POU2AF1|5450 4.266e-09 7.71e-05
CXCR5|643 4.638e-09 8.39e-05
MS4A1|931 5.536e-09 1e-04
CR2|1380 8.358e-09 0.000151
Clinical variable #5: 'NEOPLASM.DISEASESTAGE'

2 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S8.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  I OR II NOS 10
  STAGE 0 6
  STAGE I 23
  STAGE IA 10
  STAGE IB 25
  STAGE II 17
  STAGE IIA 10
  STAGE IIB 14
  STAGE IIC 10
  STAGE III 32
  STAGE IIIA 14
  STAGE IIIB 24
  STAGE IIIC 49
  STAGE IV 12
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S9.  Get Full Table List of 2 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
RAI14|26064 1.376e-06 0.0249
SEMA3E|9723 8.937e-06 0.162
Clinical variable #6: 'PATHOLOGY.T.STAGE'

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

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.43 (1.3)
  N
  0 22
  1 31
  2 60
  3 57
  4 58
     
  Significant markers N = 10
  pos. correlated 1
  neg. correlated 9
List of 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S11.  Get Full Table List of 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
INHA|3623 -0.2989 5.287e-06 0.0956
TNFSF13B|10673 -0.295 5.852e-06 0.106
GBP4|115361 -0.2936 6.53e-06 0.118
LOXL4|84171 -0.2901 8.463e-06 0.153
ANKRD22|118932 -0.2901 8.867e-06 0.16
CDK15|65061 0.3133 1.139e-05 0.206
ARHGAP25|9938 -0.2847 1.263e-05 0.228
KYNU|8942 -0.2842 1.313e-05 0.237
CXCL9|4283 -0.2815 1.603e-05 0.29
CXCL11|6373 -0.2816 1.658e-05 0.3
Clinical variable #7: 'PATHOLOGY.N.STAGE'

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

Table S12.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.88 (1.1)
  N
  0 141
  1 52
  2 34
  3 37
     
  Significant markers N = 7
  pos. correlated 2
  neg. correlated 5
List of 7 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S13.  Get Full Table List of 7 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
C12ORF62|84987 0.3035 4.998e-07 0.00904
PTPRG|5793 -0.2853 2.458e-06 0.0444
IL17RD|54756 -0.281 3.531e-06 0.0639
MAML3|55534 -0.2785 4.337e-06 0.0784
TMEM208|29100 0.2694 9.032e-06 0.163
LGR4|55366 -0.2672 1.079e-05 0.195
RNF168|165918 -0.2649 1.29e-05 0.233
Clinical variable #8: 'PATHOLOGY.M.STAGE'

No gene related to 'PATHOLOGY.M.STAGE'.

Table S14.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 254
  M1 4
  M1A 2
  M1B 2
  M1C 5
     
  Significant markers N = 0
Clinical variable #9: 'MELANOMA.ULCERATION'

No gene related to 'MELANOMA.ULCERATION'.

Table S15.  Basic characteristics of clinical feature: 'MELANOMA.ULCERATION'

MELANOMA.ULCERATION Labels N
  NO 104
  YES 74
     
  Significant markers N = 0
Clinical variable #10: 'MELANOMA.PRIMARY.KNOWN'

No gene related to 'MELANOMA.PRIMARY.KNOWN'.

Table S16.  Basic characteristics of clinical feature: 'MELANOMA.PRIMARY.KNOWN'

MELANOMA.PRIMARY.KNOWN Labels N
  NO 34
  YES 251
     
  Significant markers N = 0
Clinical variable #11: 'BRESLOW.THICKNESS'

73 genes related to 'BRESLOW.THICKNESS'.

Table S17.  Basic characteristics of clinical feature: 'BRESLOW.THICKNESS'

BRESLOW.THICKNESS Mean (SD) 3.58 (4.9)
  Significant markers N = 73
  pos. correlated 19
  neg. correlated 54
List of top 10 genes differentially expressed by 'BRESLOW.THICKNESS'

Table S18.  Get Full Table List of top 10 genes significantly correlated to 'BRESLOW.THICKNESS' by Spearman correlation test

SpearmanCorr corrP Q
TNFSF13B|10673 -0.3662 5.338e-08 0.000965
GBP4|115361 -0.3655 5.668e-08 0.00102
SLC7A8|23428 0.3539 1.57e-07 0.00284
ATP6V0A1|535 0.3495 2.293e-07 0.00415
FGL2|10875 -0.3467 2.886e-07 0.00522
CDK15|65061 0.3761 2.907e-07 0.00526
REEP6|92840 0.3423 4.186e-07 0.00757
RETSAT|54884 0.3362 6.849e-07 0.0124
GCNT1|2650 -0.3346 7.81e-07 0.0141
TRPV2|51393 0.3319 9.689e-07 0.0175
Clinical variable #12: 'GENDER'

5 genes related to 'GENDER'.

Table S19.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 110
  MALE 175
     
  Significant markers N = 5
  Higher in MALE 5
  Higher in FEMALE 0
List of 5 genes differentially expressed by 'GENDER'

Table S20.  Get Full Table List of 5 genes differentially expressed by 'GENDER'. 26 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 3382 8.877e-12 1.6e-07 0.9663
HDHD1A|8226 5150 3.949e-11 7.13e-07 0.7325
NCRNA00183|554203 5151 3.989e-11 7.21e-07 0.7324
CYORF15B|84663 2372 5.846e-09 0.000106 0.9682
CA5BP|340591 6502 4.028e-06 0.0727 0.6622
Clinical variable #13: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 5
  BLACK OR AFRICAN AMERICAN 1
  WHITE 277
     
  Significant markers N = 0
Clinical variable #14: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S22.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 3
  NOT HISPANIC OR LATINO 276
     
  Significant markers N = 0
Methods & Data
Input
  • Expresson data file = SKCM-TM.uncv2.mRNAseq_RSEM_normalized_log2.txt

  • Clinical data file = SKCM-TM.merged_data.txt

  • Number of patients = 285

  • Number of genes = 18086

  • 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

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

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

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] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[4] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[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)