Correlation between mRNAseq expression and clinical features
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C14F1PGQ
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/C14F1PGQ
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 18037 genes and 11 clinical features across 197 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

  • 22 genes correlated to 'AGE'.

    • SLC22A18AS|5003 ,  SLC22A18|5002 ,  ATPAF1|64756 ,  TNFAIP1|7126 ,  HES2|54626 ,  ...

  • 729 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • UCK2|7371 ,  KIF20A|10112 ,  BUB1|699 ,  CDCA2|157313 ,  TCTA|6988 ,  ...

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

    • BUB1|699 ,  UCK2|7371 ,  CDCA2|157313 ,  EPR1|8475 ,  PAICS|10606 ,  ...

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

    • TCTA|6988 ,  ACAD8|27034 ,  SPRED2|200734 ,  TBX18|9096 ,  CBX2|84733 ,  ...

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

    • PDZD2|23037 ,  MTSS1L|92154 ,  SLC6A1|6529 ,  ATP1A2|477 ,  LOC399959|399959 ,  ...

  • 200 genes correlated to 'GENDER'.

    • NCRNA00183|554203 ,  SLC2A9|56606 ,  HDHD1A|8226 ,  MSH6|2956 ,  NLRP6|171389 ,  ...

  • 5 genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • MS4A1|931 ,  LOC646471|646471 ,  KLHL5|51088 ,  DALRD3|55152 ,  TMSB4Y|9087

  • 1 gene correlated to 'NUMBERPACKYEARSSMOKED'.

    • STK4|6789

  • 8 genes correlated to 'RACE'.

    • NOTCH2NL|388677 ,  CRYBB2|1415 ,  RPL23AP7|118433 ,  ARMC10|83787 ,  LRRC37A2|474170 ,  ...

  • No genes correlated to 'Time to Death', 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 to Death Cox regression test   N=0        
AGE Spearman correlation test N=22 older N=13 younger N=9
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=729        
PATHOLOGY T STAGE Spearman correlation test N=935 higher stage N=560 lower stage N=375
PATHOLOGY N STAGE Spearman correlation test N=42 higher stage N=28 lower stage N=14
PATHOLOGY M STAGE Kruskal-Wallis test N=6        
GENDER Wilcoxon test N=200 male N=200 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=5 higher score N=2 lower score N=3
NUMBERPACKYEARSSMOKED Spearman correlation test N=1 higher numberpackyearssmoked N=1 lower numberpackyearssmoked N=0
RACE Kruskal-Wallis test N=8        
ETHNICITY Wilcoxon test   N=0        
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 (Years) 2-5925 (median=510.5)
  censored N = 165
  death N = 7
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

22 genes related to 'AGE'.

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

AGE Mean (SD) 59.89 (12)
  Significant markers N = 22
  pos. correlated 13
  neg. correlated 9
List of top 10 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
SLC22A18AS|5003 0.357 3.229e-07 0.00582
SLC22A18|5002 0.3556 3.624e-07 0.00654
ATPAF1|64756 0.3439 9.095e-07 0.0164
TNFAIP1|7126 -0.3394 1.292e-06 0.0233
HES2|54626 0.3412 1.36e-06 0.0245
HIBCH|26275 0.337 1.549e-06 0.0279
ZBED2|79413 -0.3407 2.361e-06 0.0426
FOXQ1|94234 0.3255 3.65e-06 0.0658
PADI1|29943 -0.3316 4.25e-06 0.0766
ADAMTS3|9508 -0.3186 5.982e-06 0.108
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

729 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 120
  STAGE II 12
  STAGE III 42
  STAGE IV 12
     
  Significant markers N = 729
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

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

ANOVA_P Q
UCK2|7371 7.475e-13 1.35e-08
KIF20A|10112 9.528e-13 1.72e-08
BUB1|699 1.052e-12 1.9e-08
CDCA2|157313 1.123e-12 2.02e-08
TCTA|6988 1.159e-12 2.09e-08
CENPA|1058 1.199e-12 2.16e-08
EPR1|8475 1.603e-12 2.89e-08
ASPM|259266 2.653e-12 4.78e-08
CENPF|1063 3.12e-12 5.63e-08
MKI67|4288 3.153e-12 5.68e-08
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 1.61 (0.89)
  N
  1 128
  2 19
  3 48
  4 2
     
  Significant markers N = 935
  pos. correlated 560
  neg. correlated 375
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
BUB1|699 0.5202 4.712e-15 8.5e-11
UCK2|7371 0.5018 5.823e-14 1.05e-09
CDCA2|157313 0.4983 1.065e-13 1.92e-09
EPR1|8475 0.4936 2.601e-13 4.69e-09
PAICS|10606 0.4843 5.581e-13 1.01e-08
CENPA|1058 0.482 7.415e-13 1.34e-08
PABPC1|26986 0.4817 7.716e-13 1.39e-08
TPX2|22974 0.4796 9.954e-13 1.79e-08
ASPM|259266 0.4778 1.251e-12 2.26e-08
NUF2|83540 0.4749 1.784e-12 3.22e-08
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.5 (0.63)
  N
  0 32
  1 20
  2 4
     
  Significant markers N = 42
  pos. correlated 28
  neg. correlated 14
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
TCTA|6988 -0.6411 1.022e-07 0.00184
ACAD8|27034 -0.6384 1.199e-07 0.00216
SPRED2|200734 0.6194 3.592e-07 0.00648
TBX18|9096 0.6244 7.561e-07 0.0136
CBX2|84733 0.6011 9.63e-07 0.0174
FOXRED1|55572 -0.5968 1.208e-06 0.0218
PABPC1|26986 0.5887 1.826e-06 0.0329
STRA6|64220 0.5974 1.853e-06 0.0334
MLYCD|23417 -0.5873 1.959e-06 0.0353
NAP1L1|4673 0.5857 2.117e-06 0.0382
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 83
  M1 8
  MX 93
     
  Significant markers N = 6
List of 6 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of 6 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
PDZD2|23037 1.723e-06 0.0311
MTSS1L|92154 3.061e-06 0.0552
SLC6A1|6529 6.666e-06 0.12
ATP1A2|477 1.419e-05 0.256
LOC399959|399959 1.513e-05 0.273
GRIK3|2899 1.665e-05 0.3
Clinical variable #7: 'GENDER'

200 genes related to 'GENDER'.

Table S12.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 58
  MALE 139
     
  Significant markers N = 200
  Higher in MALE 200
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 62 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 1428 9.64e-13 1.74e-08 0.8229
SLC2A9|56606 6607 1.647e-12 2.97e-08 0.8195
HDHD1A|8226 1462 1.891e-12 3.41e-08 0.8187
MSH6|2956 1546 9.624e-12 1.73e-07 0.8082
NLRP6|171389 6184 7.118e-11 1.28e-06 0.7977
AOX1|316 6394 9.325e-11 1.68e-06 0.7931
CCDC146|57639 6310 4.179e-10 7.53e-06 0.7827
ZMYND12|84217 6271 8.238e-10 1.48e-05 0.7778
ANKRD2|26287 6195 2.995e-09 5.39e-05 0.7684
KIF3C|3797 1929 8.317e-09 0.00015 0.7607
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

5 genes related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S14.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 91.48 (16)
  Significant markers N = 5
  pos. correlated 2
  neg. correlated 3
List of 5 genes differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S15.  Get Full Table List of 5 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
MS4A1|931 -0.6202 1.209e-06 0.0218
LOC646471|646471 0.5829 4.654e-06 0.0839
KLHL5|51088 -0.5648 8.619e-06 0.155
DALRD3|55152 0.5569 1.221e-05 0.22
TMSB4Y|9087 -0.6518 1.658e-05 0.299
Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

One gene related to 'NUMBERPACKYEARSSMOKED'.

Table S16.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 30.72 (35)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene differentially expressed by 'NUMBERPACKYEARSSMOKED'

Table S17.  Get Full Table List of one gene significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
STK4|6789 0.7641 8.781e-06 0.158
Clinical variable #10: 'RACE'

8 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 2
  ASIAN 4
  BLACK OR AFRICAN AMERICAN 47
  WHITE 130
     
  Significant markers N = 8
List of 8 genes differentially expressed by 'RACE'

Table S19.  Get Full Table List of 8 genes differentially expressed by 'RACE'

ANOVA_P Q
NOTCH2NL|388677 1.465e-11 2.64e-07
CRYBB2|1415 1.138e-06 0.0205
RPL23AP7|118433 1.889e-06 0.0341
ARMC10|83787 2.121e-06 0.0383
LRRC37A2|474170 2.28e-06 0.0411
FLT3|2322 5.452e-06 0.0983
LOC90784|90784 7.778e-06 0.14
ACSM1|116285 8.911e-06 0.161
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S20.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 9
  NOT HISPANIC OR LATINO 152
     
  Significant markers N = 0
Methods & Data
Input

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

  • Clinical data file = KIRP-TP.merged_data.txt

  • Number of patients = 197

  • Number of genes = 18037

  • Number of clinical features = 11

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)
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