Correlation between mRNAseq expression and clinical features
Kidney Renal Papillary Cell Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1X63KS0
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/C1X63KS0
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 17999 genes and 11 clinical features across 222 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 27 genes correlated to 'AGE'.

    • TNFAIP1|7126 ,  SLC22A18|5002 ,  SLC22A18AS|5003 ,  LRRC37B2|147172 ,  SMARCE1|6605 ,  ...

  • 672 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • KIF20A|10112 ,  EPR1|8475 ,  UCK2|7371 ,  CENPA|1058 ,  NEK2|4751 ,  ...

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

    • BUB1|699 ,  UCK2|7371 ,  EPR1|8475 ,  CDCA2|157313 ,  NEK2|4751 ,  ...

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

    • ACAD8|27034 ,  SPRED2|200734 ,  TBX18|9096 ,  TCTA|6988 ,  SRPX|8406 ,  ...

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

    • PDZD2|23037 ,  TMTC1|83857 ,  MTSS1L|92154 ,  TMEM98|26022 ,  NEURL1B|54492

  • 209 genes correlated to 'GENDER'.

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

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

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

  • 12 genes correlated to 'RACE'.

    • NOTCH2NL|388677 ,  LRRC37A2|474170 ,  CRYBB2|1415 ,  BEGAIN|57596 ,  LOC90784|90784 ,  ...

  • No genes correlated to 'Time to Death', 'NUMBERPACKYEARSSMOKED', 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=27 older N=17 younger N=10
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=672        
PATHOLOGY T STAGE Spearman correlation test N=931 higher stage N=572 lower stage N=359
PATHOLOGY N STAGE Spearman correlation test N=101 higher stage N=79 lower stage N=22
PATHOLOGY M STAGE Kruskal-Wallis test N=5        
GENDER Wilcoxon test N=209 male N=209 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=9 higher score N=4 lower score N=5
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
RACE Kruskal-Wallis test N=12        
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=541)
  censored N = 188
  death N = 7
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

27 genes related to 'AGE'.

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

AGE Mean (SD) 60.47 (12)
  Significant markers N = 27
  pos. correlated 17
  neg. correlated 10
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
TNFAIP1|7126 -0.3509 1.102e-07 0.00198
SLC22A18|5002 0.3445 1.927e-07 0.00347
SLC22A18AS|5003 0.3438 2.061e-07 0.00371
LRRC37B2|147172 -0.3293 6.992e-07 0.0126
SMARCE1|6605 -0.3273 8.199e-07 0.0148
HES2|54626 0.3234 1.336e-06 0.024
HIBCH|26275 0.3192 1.575e-06 0.0283
ATPAF1|64756 0.3138 2.409e-06 0.0434
LDHD|197257 0.3087 3.575e-06 0.0643
PCCB|5096 0.3076 3.892e-06 0.07
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

672 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 138
  STAGE II 16
  STAGE III 43
  STAGE IV 13
     
  Significant markers N = 672
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
KIF20A|10112 5.851e-14 1.05e-09
EPR1|8475 1.292e-13 2.32e-09
UCK2|7371 2.299e-13 4.14e-09
CENPA|1058 3.671e-13 6.61e-09
NEK2|4751 3.755e-13 6.76e-09
CDCA2|157313 3.835e-13 6.9e-09
KIFC1|3833 4.458e-13 8.02e-09
CENPF|1063 6.29e-13 1.13e-08
NCAPG|64151 6.515e-13 1.17e-08
TPX2|22974 7.32e-13 1.32e-08
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 1.57 (0.86)
  N
  1 147
  2 22
  3 49
  4 2
     
  Significant markers N = 931
  pos. correlated 572
  neg. correlated 359
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 0.4973 3.824e-15 6.88e-11
UCK2|7371 0.4877 1.513e-14 2.72e-10
EPR1|8475 0.4881 2.861e-14 5.15e-10
CDCA2|157313 0.4783 6.379e-14 1.15e-09
NEK2|4751 0.4789 6.691e-14 1.2e-09
TPX2|22974 0.4681 2.215e-13 3.99e-09
PABPC1|26986 0.4665 2.733e-13 4.92e-09
NUF2|83540 0.4656 3.107e-13 5.59e-09
CENPA|1058 0.4638 3.911e-13 7.04e-09
EXO1|9156 0.4631 4.267e-13 7.68e-09
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.44 (0.62)
  N
  0 39
  1 20
  2 4
     
  Significant markers N = 101
  pos. correlated 79
  neg. correlated 22
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
ACAD8|27034 -0.6586 4.426e-09 7.97e-05
SPRED2|200734 0.6082 1.24e-07 0.00223
TBX18|9096 0.6234 1.339e-07 0.00241
TCTA|6988 -0.6028 1.712e-07 0.00308
SRPX|8406 0.5955 2.63e-07 0.00473
C9ORF140|89958 0.5938 2.908e-07 0.00523
GBA2|57704 -0.5858 4.564e-07 0.00821
STRA6|64220 0.5975 4.655e-07 0.00838
HJURP|55355 0.5802 6.25e-07 0.0112
SPATA18|132671 -0.5789 6.709e-07 0.0121
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 89
  M1 8
  MX 112
     
  Significant markers N = 5
List of 5 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of 5 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
PDZD2|23037 4.302e-06 0.0774
TMTC1|83857 5.25e-06 0.0945
MTSS1L|92154 8.166e-06 0.147
TMEM98|26022 9.865e-06 0.178
NEURL1B|54492 1.552e-05 0.279
Clinical variable #7: 'GENDER'

209 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 63
  MALE 159
     
  Significant markers N = 209
  Higher in MALE 209
  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'. 68 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
NCRNA00183|554203 1716 2.346e-14 4.22e-10 0.8287
HDHD1A|8226 1720 2.521e-14 4.53e-10 0.8283
SLC2A9|56606 7994 4.564e-12 8.21e-08 0.798
NLRP6|171389 7650 2.133e-11 3.83e-07 0.7909
MSH6|2956 2129 2.509e-11 4.51e-07 0.7875
CCDC146|57639 7814 7.961e-11 1.43e-06 0.7801
AOX1|316 7771 1.537e-10 2.76e-06 0.7758
ANKRD2|26287 7638 1.105e-09 1.99e-05 0.7625
FAM155A|728215 2195 2.581e-09 4.64e-05 0.7608
ZMYND12|84217 7526 5.417e-09 9.73e-05 0.7513
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

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

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

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 91.75 (16)
  Significant markers N = 9
  pos. correlated 4
  neg. correlated 5
List of 9 genes differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S15.  Get Full Table List of 9 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
MS4A1|931 -0.6323 2.925e-07 0.00527
KLHL5|51088 -0.5762 2.731e-06 0.0492
LOC646471|646471 0.5805 2.736e-06 0.0492
DALRD3|55152 0.5713 3.459e-06 0.0623
TMSB4Y|9087 -0.6585 5.189e-06 0.0934
TTC21A|199223 0.559 6.201e-06 0.112
C2ORF69|205327 -0.5455 1.145e-05 0.206
LY75|4065 -0.5418 1.349e-05 0.243
P4HTM|54681 0.5377 1.61e-05 0.29
Clinical variable #9: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 33.44 (34)
  Significant markers N = 0
Clinical variable #10: 'RACE'

12 genes related to 'RACE'.

Table S17.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 2
  ASIAN 5
  BLACK OR AFRICAN AMERICAN 52
  WHITE 148
     
  Significant markers N = 12
List of top 10 genes differentially expressed by 'RACE'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
NOTCH2NL|388677 7.563e-11 1.36e-06
LRRC37A2|474170 9.874e-08 0.00178
CRYBB2|1415 2.307e-07 0.00415
BEGAIN|57596 3.933e-07 0.00708
LOC90784|90784 6.751e-07 0.0121
ARMC10|83787 1.143e-06 0.0206
GSTM3|2947 4.472e-06 0.0805
RPL23AP7|118433 1.122e-05 0.202
ARL17A|51326 1.183e-05 0.213
CN5H6.4|150384 1.224e-05 0.22
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 9
  NOT HISPANIC OR LATINO 176
     
  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 = 222

  • Number of genes = 17999

  • 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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