Kidney Renal Clear Cell Carcinoma: Correlation between mRNAseq expression and clinical features
Maintained by Juok Cho (Broad Institute)
Overview
Introduction

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

Summary

Testing the association between 18300 genes and 8 clinical features across 469 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 2173 genes correlated to 'Time to Death'.

    • B3GNTL1|146712 ,  COL7A1|1294 ,  DONSON|29980 ,  ANKRD56|345079 ,  ADAMTS14|140766 ,  ...

  • 15 genes correlated to 'AGE'.

    • RANBP17|64901 ,  WFDC1|58189 ,  RFPL1S|10740 ,  PALLD|23022 ,  NEFH|4744 ,  ...

  • 215 genes correlated to 'GENDER'.

    • XIST|7503 ,  PRKY|5616 ,  NLGN4Y|22829 ,  RPS4Y1|6192 ,  TSIX|9383 ,  ...

  • 2360 genes correlated to 'PATHOLOGY.T'.

    • NR3C2|4306 ,  FAM122A|116224 ,  FKBP11|51303 ,  TMEM150C|441027 ,  PLEKHA9|51054 ,  ...

  • 5 genes correlated to 'PATHOLOGY.N'.

    • C11ORF34|349633 ,  PITX2|5308 ,  ATP6V1D|51382 ,  HEMGN|55363 ,  TMEM104|54868

  • 281 genes correlated to 'PATHOLOGICSPREAD(M)'.

    • GARNL3|84253 ,  IL20RB|53833 ,  PLEKHA9|51054 ,  C22ORF9|23313 ,  BIRC5|332 ,  ...

  • 2828 genes correlated to 'TUMOR.STAGE'.

    • PLEKHA9|51054 ,  NR3C2|4306 ,  FKBP11|51303 ,  FAM122A|116224 ,  TSPAN7|7102 ,  ...

  • No genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'

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=2173 shorter survival N=1406 longer survival N=767
AGE Spearman correlation test N=15 older N=0 younger N=15
GENDER t test N=215 male N=136 female N=79
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
PATHOLOGY T Spearman correlation test N=2360 higher pT N=1276 lower pT N=1084
PATHOLOGY N t test N=5 n1 N=2 n0 N=3
PATHOLOGICSPREAD(M) t test N=281 m1 N=236 m0 N=45
TUMOR STAGE Spearman correlation test N=2828 higher stage N=1549 lower stage N=1279
Clinical variable #1: 'Time to Death'

2173 genes related to 'Time to Death'.

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

Time to Death Duration (Months) 0.1-111 (median=34.3)
  censored N = 312
  death N = 154
     
  Significant markers N = 2173
  associated with shorter survival 1406
  associated with longer survival 767
List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

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

HazardRatio Wald_P Q C_index
B3GNTL1|146712 2.4 0 0 0.68
COL7A1|1294 1.31 0 0 0.672
DONSON|29980 2.6 0 0 0.682
ANKRD56|345079 0.71 1.11e-16 2e-12 0.322
ADAMTS14|140766 1.43 4.441e-16 8.1e-12 0.68
NUMBL|9253 1.84 4.441e-16 8.1e-12 0.685
RGS17|26575 1.43 4.441e-16 8.1e-12 0.665
CDCA3|83461 1.68 6.661e-16 1.2e-11 0.669
SLC16A12|387700 0.79 6.661e-16 1.2e-11 0.317
FBXL5|26234 0.42 8.882e-16 1.6e-11 0.324

Figure S1.  Get High-res Image As an example, this figure shows the association of B3GNTL1|146712 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 0 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

15 genes related to 'AGE'.

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

AGE Mean (SD) 60.59 (12)
  Significant markers N = 15
  pos. correlated 0
  neg. correlated 15
List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
RANBP17|64901 -0.2635 7.124e-09 0.00013
WFDC1|58189 -0.2521 3.214e-08 0.000588
RFPL1S|10740 -0.2493 5.839e-08 0.00107
PALLD|23022 -0.2388 1.722e-07 0.00315
NEFH|4744 -0.2312 4.278e-07 0.00783
UTY|7404 -0.2641 4.804e-07 0.00879
DIO2|1734 -0.23 5.024e-07 0.00919
FNDC1|84624 -0.2269 7.008e-07 0.0128
ZNF610|162963 -0.2206 1.439e-06 0.0263
USP9Y|8287 -0.2472 1.632e-06 0.0298

Figure S2.  Get High-res Image As an example, this figure shows the association of RANBP17|64901 to 'AGE'. P value = 7.12e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

215 genes related to 'GENDER'.

Table S5.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 162
  MALE 307
     
  Significant markers N = 215
  Higher in MALE 136
  Higher in FEMALE 79
List of top 10 genes differentially expressed by 'GENDER'

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

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503 -42.39 2.021e-155 3.7e-151 0.9817
PRKY|5616 37.3 1.011e-100 1.85e-96 0.9791
NLGN4Y|22829 33.57 5.666e-72 1.04e-67 0.9742
RPS4Y1|6192 34.21 5.279e-69 9.66e-65 0.9855
TSIX|9383 -23.5 1.788e-67 3.27e-63 0.9663
ZFY|7544 33.4 1.055e-61 1.93e-57 0.9774
DDX3Y|8653 29.35 4.141e-54 7.58e-50 0.9732
KDM5C|8242 -16.63 1.397e-47 2.56e-43 0.8949
NCRNA00183|554203 -16.16 7.263e-44 1.33e-39 0.8655
KDM5D|8284 23.9 3.025e-37 5.53e-33 0.97

Figure S3.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 2.02e-155 with T-test analysis.

Clinical variable #4: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S7.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 90.97 (19)
  Score N
  0 1
  70 1
  80 3
  90 9
  100 17
     
  Significant markers N = 0
Clinical variable #5: 'PATHOLOGY.T'

2360 genes related to 'PATHOLOGY.T'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T Mean (SD) 1.93 (0.97)
  N
  T1 228
  T2 59
  T3 171
  T4 11
     
  Significant markers N = 2360
  pos. correlated 1276
  neg. correlated 1084
List of top 10 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

SpearmanCorr corrP Q
NR3C2|4306 -0.4028 1.007e-19 1.84e-15
FAM122A|116224 -0.3813 1.11e-17 2.03e-13
FKBP11|51303 0.3802 1.403e-17 2.57e-13
TMEM150C|441027 -0.376 3.376e-17 6.18e-13
PLEKHA9|51054 0.3745 4.597e-17 8.41e-13
ZNF132|7691 -0.3731 6.16e-17 1.13e-12
FAM160A1|729830 -0.37 1.16e-16 2.12e-12
ACADSB|36 -0.3678 1.791e-16 3.28e-12
CCDC121|79635 -0.3671 2.06e-16 3.77e-12
ANKRD56|345079 -0.3625 5.53e-16 1.01e-11

Figure S4.  Get High-res Image As an example, this figure shows the association of NR3C2|4306 to 'PATHOLOGY.T'. P value = 1.01e-19 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.N'

5 genes related to 'PATHOLOGY.N'.

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

PATHOLOGY.N Labels N
  N0 224
  N1 17
     
  Significant markers N = 5
  Higher in N1 2
  Higher in N0 3
List of 5 genes differentially expressed by 'PATHOLOGY.N'

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

T(pos if higher in 'N1') ttestP Q AUC
C11ORF34|349633 -7.86 3.591e-09 6.57e-05 0.7246
PITX2|5308 6.94 1.791e-07 0.00328 0.7869
ATP6V1D|51382 -6.12 3.87e-07 0.00708 0.7503
HEMGN|55363 -5.84 1.013e-06 0.0185 0.7421
TMEM104|54868 5.93 2.441e-06 0.0446 0.8025

Figure S5.  Get High-res Image As an example, this figure shows the association of C11ORF34|349633 to 'PATHOLOGY.N'. P value = 3.59e-09 with T-test analysis.

Clinical variable #7: 'PATHOLOGICSPREAD(M)'

281 genes related to 'PATHOLOGICSPREAD(M)'.

Table S12.  Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) Labels N
  M0 392
  M1 77
     
  Significant markers N = 281
  Higher in M1 236
  Higher in M0 45
List of top 10 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

T(pos if higher in 'M1') ttestP Q AUC
GARNL3|84253 -7.02 1.643e-10 3.01e-06 0.7468
IL20RB|53833 6.67 1.26e-09 2.31e-05 0.7307
PLEKHA9|51054 6.59 1.665e-09 3.05e-05 0.7361
C22ORF9|23313 6.56 1.728e-09 3.16e-05 0.7333
BIRC5|332 6.55 2.215e-09 4.05e-05 0.727
INHBE|83729 6.47 3.65e-09 6.68e-05 0.7247
TYMP|1890 6.33 3.802e-09 6.96e-05 0.7083
NFE2L3|9603 6.36 4.534e-09 8.29e-05 0.7207
OIP5|11339 6.31 5.952e-09 0.000109 0.7241
CENPA|1058 6.31 7.458e-09 0.000136 0.722

Figure S6.  Get High-res Image As an example, this figure shows the association of GARNL3|84253 to 'PATHOLOGICSPREAD(M)'. P value = 1.64e-10 with T-test analysis.

Clinical variable #8: 'TUMOR.STAGE'

2828 genes related to 'TUMOR.STAGE'.

Table S14.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 2.12 (1.2)
  N
  Stage 1 224
  Stage 2 47
  Stage 3 117
  Stage 4 81
     
  Significant markers N = 2828
  pos. correlated 1549
  neg. correlated 1279
List of top 10 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

Table S15.  Get Full Table List of top 10 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
PLEKHA9|51054 0.4077 3.33e-20 6.09e-16
NR3C2|4306 -0.4075 3.484e-20 6.37e-16
FKBP11|51303 0.3986 2.591e-19 4.74e-15
FAM122A|116224 -0.3977 3.189e-19 5.83e-15
TSPAN7|7102 -0.3805 1.332e-17 2.44e-13
NOP2|4839 0.3778 2.311e-17 4.23e-13
ACADSB|36 -0.3776 2.436e-17 4.46e-13
FAM160A1|729830 -0.3775 2.464e-17 4.51e-13
ALDH6A1|4329 -0.3762 3.227e-17 5.9e-13
TRAF6|7189 -0.3759 3.451e-17 6.31e-13

Figure S7.  Get High-res Image As an example, this figure shows the association of PLEKHA9|51054 to 'TUMOR.STAGE'. P value = 3.33e-20 with Spearman correlation analysis.

Methods & Data
Input

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

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

  • Number of patients = 469

  • Number of genes = 18300

  • Number of clinical features = 8

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

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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] 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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