Correlation between mRNAseq expression and clinical features
Skin Cutaneous Melanoma (Metastatic)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1MG7N6P
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/C1MG7N6P
Overview
Introduction

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

Summary

Testing the association between 18084 genes and 12 clinical features across 271 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 6 genes correlated to 'AGE'.

    • ACOX2|8309 ,  FAM84B|157638 ,  MAOB|4129 ,  PRDX6|9588 ,  CMBL|134147 ,  ...

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

    • TMEM156|80008 ,  POU2AF1|5450 ,  IGJ|3512 ,  FCRL5|83416 ,  RBP5|83758 ,  ...

  • 1 gene correlated to 'NEOPLASM.DISEASESTAGE'.

    • RAI14|26064

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

    • C12ORF62|84987 ,  ZNF131|7690

  • 1 gene correlated to 'PATHOLOGY.M.STAGE'.

    • LRRC28|123355

  • 8 genes correlated to 'BRESLOW.THICKNESS'.

    • GBP4|115361 ,  REEP6|92840 ,  TNFSF13B|10673 ,  GCNT1|2650 ,  SLC7A8|23428 ,  ...

  • 28 genes correlated to 'GENDER'.

    • ZFY|7544 ,  PRKY|5616 ,  XIST|7503 ,  RPS4Y1|6192 ,  DDX3Y|8653 ,  ...

  • No genes correlated to 'Time from Specimen Diagnosis to Death', 'Time to Death', 'PATHOLOGY.T.STAGE', 'MELANOMA.ULCERATION', and 'MELANOMA.PRIMARY.KNOWN'.

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 from Specimen Diagnosis to Death Cox regression test   N=0        
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=6 older N=0 younger N=6
PRIMARY SITE OF DISEASE ANOVA test N=219        
NEOPLASM DISEASESTAGE ANOVA test N=1        
PATHOLOGY T STAGE Spearman correlation test   N=0        
PATHOLOGY N STAGE Spearman correlation test N=2 higher stage N=1 lower stage N=1
PATHOLOGY M STAGE ANOVA test N=1        
MELANOMA ULCERATION t test   N=0        
MELANOMA PRIMARY KNOWN t test   N=0        
BRESLOW THICKNESS Spearman correlation test N=8 higher breslow.thickness N=4 lower breslow.thickness N=4
GENDER t test N=28 male N=15 female N=13
Clinical variable #1: 'Time from Specimen Diagnosis to Death'

No gene 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=13.7)
  censored N = 133
  death N = 127
     
  Significant markers N = 0
Clinical variable #2: 'Time to Death'

No gene related to 'Time to Death'.

Table S2.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0.2-357.4 (median=47.5)
  censored N = 138
  death N = 128
     
  Significant markers N = 0
Clinical variable #3: 'AGE'

6 genes related to 'AGE'.

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

AGE Mean (SD) 55.56 (16)
  Significant markers N = 6
  pos. correlated 0
  neg. correlated 6
List of 6 genes significantly correlated to 'AGE' by Spearman correlation test

Table S4.  Get Full Table List of 6 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
ACOX2|8309 -0.3277 4.211e-08 0.000762
FAM84B|157638 -0.2967 7.93e-07 0.0143
MAOB|4129 -0.2961 8.402e-07 0.0152
PRDX6|9588 -0.2867 1.909e-06 0.0345
CMBL|134147 -0.2867 1.912e-06 0.0346
PPP1R1B|84152 -0.2979 2.265e-06 0.041

Figure S1.  Get High-res Image As an example, this figure shows the association of ACOX2|8309 to 'AGE'. P value = 4.21e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #4: 'PRIMARY.SITE.OF.DISEASE'

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

Table S5.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  DISTANT METASTASIS 36
  PRIMARY TUMOR 1
  REGIONAL CUTANEOUS OR SUBCUTANEOUS TISSUE 59
  REGIONAL LYMPH NODE 174
     
  Significant markers N = 219
List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

ANOVA_P Q
TMEM156|80008 4.06e-12 7.34e-08
POU2AF1|5450 2.79e-11 5.05e-07
IGJ|3512 9.943e-11 1.8e-06
FCRL5|83416 1.604e-10 2.9e-06
RBP5|83758 1.929e-10 3.49e-06
CD38|952 2.51e-10 4.54e-06
SHISA3|152573 3.51e-10 6.35e-06
C7|730 4.982e-10 9.01e-06
MYO7B|4648 7.729e-10 1.4e-05
P2RY10|27334 9.975e-10 1.8e-05

Figure S2.  Get High-res Image As an example, this figure shows the association of TMEM156|80008 to 'PRIMARY.SITE.OF.DISEASE'. P value = 4.06e-12 with ANOVA analysis.

Clinical variable #5: 'NEOPLASM.DISEASESTAGE'

One gene related to 'NEOPLASM.DISEASESTAGE'.

Table S7.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  I OR II NOS 10
  STAGE 0 6
  STAGE I 22
  STAGE IA 10
  STAGE IB 25
  STAGE II 17
  STAGE IIA 10
  STAGE IIB 14
  STAGE IIC 10
  STAGE III 30
  STAGE IIIA 11
  STAGE IIIB 23
  STAGE IIIC 44
  STAGE IV 12
     
  Significant markers N = 1
List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S8.  Get Full Table List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
RAI14|26064 1.444e-06 0.0261

Figure S3.  Get High-res Image As an example, this figure shows the association of RAI14|26064 to 'NEOPLASM.DISEASESTAGE'. P value = 1.44e-06 with ANOVA analysis.

Clinical variable #6: 'PATHOLOGY.T.STAGE'

No gene related to 'PATHOLOGY.T.STAGE'.

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.4 (1.3)
  N
  0 22
  1 30
  2 59
  3 52
  4 54
     
  Significant markers N = 0
Clinical variable #7: 'PATHOLOGY.N.STAGE'

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

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.83 (1.1)
  N
  0 139
  1 48
  2 31
  3 33
     
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S11.  Get Full Table List of 2 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
C12ORF62|84987 0.3096 5.624e-07 0.0102
ZNF131|7690 -0.2982 1.505e-06 0.0272

Figure S4.  Get High-res Image As an example, this figure shows the association of C12ORF62|84987 to 'PATHOLOGY.N.STAGE'. P value = 5.62e-07 with Spearman correlation analysis.

Clinical variable #8: 'PATHOLOGY.M.STAGE'

One gene related to 'PATHOLOGY.M.STAGE'.

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

PATHOLOGY.M.STAGE Labels N
  M0 242
  M1 4
  M1A 2
  M1B 2
  M1C 5
     
  Significant markers N = 1
List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

Table S13.  Get Full Table List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
LRRC28|123355 4.002e-07 0.00724

Figure S5.  Get High-res Image As an example, this figure shows the association of LRRC28|123355 to 'PATHOLOGY.M.STAGE'. P value = 4e-07 with ANOVA analysis.

Clinical variable #9: 'MELANOMA.ULCERATION'

No gene related to 'MELANOMA.ULCERATION'.

Table S14.  Basic characteristics of clinical feature: 'MELANOMA.ULCERATION'

MELANOMA.ULCERATION Labels N
  NO 100
  YES 68
     
  Significant markers N = 0
Clinical variable #10: 'MELANOMA.PRIMARY.KNOWN'

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

Table S15.  Basic characteristics of clinical feature: 'MELANOMA.PRIMARY.KNOWN'

MELANOMA.PRIMARY.KNOWN Labels N
  NO 32
  YES 239
     
  Significant markers N = 0
Clinical variable #11: 'BRESLOW.THICKNESS'

8 genes related to 'BRESLOW.THICKNESS'.

Table S16.  Basic characteristics of clinical feature: 'BRESLOW.THICKNESS'

BRESLOW.THICKNESS Mean (SD) 3.54 (5)
  Significant markers N = 8
  pos. correlated 4
  neg. correlated 4
List of 8 genes significantly correlated to 'BRESLOW.THICKNESS' by Spearman correlation test

Table S17.  Get Full Table List of 8 genes significantly correlated to 'BRESLOW.THICKNESS' by Spearman correlation test

SpearmanCorr corrP Q
GBP4|115361 -0.3589 2.084e-07 0.00377
REEP6|92840 0.3506 4.108e-07 0.00743
TNFSF13B|10673 -0.3394 1.003e-06 0.0181
GCNT1|2650 -0.3371 1.194e-06 0.0216
SLC7A8|23428 0.3335 1.578e-06 0.0285
CRTAP|10491 0.3326 1.687e-06 0.0305
FGL2|10875 -0.3292 2.183e-06 0.0395
CDK15|65061 0.3566 2.404e-06 0.0435

Figure S6.  Get High-res Image As an example, this figure shows the association of GBP4|115361 to 'BRESLOW.THICKNESS'. P value = 2.08e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #12: 'GENDER'

28 genes related to 'GENDER'.

Table S18.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 103
  MALE 168
     
  Significant markers N = 28
  Higher in MALE 15
  Higher in FEMALE 13
List of top 10 genes differentially expressed by 'GENDER'

Table S19.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
ZFY|7544 42.7 1.671e-111 3.02e-107 0.9989
PRKY|5616 35.22 8.999e-90 1.63e-85 0.9976
XIST|7503 -24.72 9.157e-66 1.66e-61 0.9626
RPS4Y1|6192 36.9 5.046e-65 9.12e-61 1
DDX3Y|8653 41.22 9.106e-64 1.65e-59 1
EIF1AY|9086 43.53 3.057e-58 5.52e-54 1
KDM5D|8284 39.06 4.096e-52 7.4e-48 1
UTY|7404 35.55 5.798e-47 1.05e-42 1
USP9Y|8287 33.66 6.306e-44 1.14e-39 0.9996
TSIX|9383 -17.16 3.558e-41 6.43e-37 0.9534

Figure S7.  Get High-res Image As an example, this figure shows the association of ZFY|7544 to 'GENDER'. P value = 1.67e-111 with T-test analysis.

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 = 271

  • Number of genes = 18084

  • 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

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)
Copyright © 2014 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle