Kidney Renal Clear Cell Carcinoma: Correlation between mRNAseq expression and clinical features
(primary solid tumor cohort)
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 18295 genes and 8 clinical features across 480 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 2315 genes correlated to 'Time to Death'.

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

  • 19 genes correlated to 'AGE'.

    • RANBP17|64901 ,  RFPL1S|10740 ,  WFDC1|58189 ,  UTY|7404 ,  PALLD|23022 ,  ...

  • 216 genes correlated to 'GENDER'.

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

  • 2625 genes correlated to 'PATHOLOGY.T'.

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

  • 5 genes correlated to 'PATHOLOGY.N'.

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

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

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

  • 3057 genes correlated to 'TUMOR.STAGE'.

    • PLEKHA9|51054 ,  NR3C2|4306 ,  FKBP11|51303 ,  FAM122A|116224 ,  NOP2|4839 ,  ...

  • 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=2315 shorter survival N=1496 longer survival N=819
AGE Spearman correlation test N=19 older N=3 younger N=16
GENDER t test N=216 male N=134 female N=82
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
PATHOLOGY T Spearman correlation test N=2625 higher pT N=1420 lower pT N=1205
PATHOLOGY N t test N=5 n1 N=2 n0 N=3
PATHOLOGICSPREAD(M) t test N=317 m1 N=264 m0 N=53
TUMOR STAGE Spearman correlation test N=3057 higher stage N=1674 lower stage N=1383
Clinical variable #1: 'Time to Death'

2315 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 = 323
  death N = 154
     
  Significant markers N = 2315
  associated with shorter survival 1496
  associated with longer survival 819
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
ANKRD56|345079 0.71 0 0 0.319
B3GNTL1|146712 2.4 0 0 0.684
COL7A1|1294 1.32 0 0 0.676
DONSON|29980 2.7 0 0 0.686
ADAMTS14|140766 1.44 1.11e-16 2e-12 0.684
SLC16A12|387700 0.78 1.11e-16 2e-12 0.311
NUMBL|9253 1.85 2.22e-16 4.1e-12 0.687
ANAPC7|51434 5.8 3.331e-16 6.1e-12 0.677
STX1A|6804 1.73 3.331e-16 6.1e-12 0.678
RGS17|26575 1.43 4.441e-16 8.1e-12 0.666

Figure S1.  Get High-res Image As an example, this figure shows the association of ANKRD56|345079 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'

19 genes related to 'AGE'.

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

AGE Mean (SD) 60.58 (12)
  Significant markers N = 19
  pos. correlated 3
  neg. correlated 16
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 -0.2556 1.392e-08 0.000255
RFPL1S|10740 -0.2559 1.702e-08 0.000311
WFDC1|58189 -0.2476 3.998e-08 0.000731
UTY|7404 -0.2758 1.044e-07 0.00191
PALLD|23022 -0.2349 1.983e-07 0.00363
NEFH|4744 -0.2324 2.701e-07 0.00494
DIO2|1734 -0.2285 4.416e-07 0.00808
FNDC1|84624 -0.2249 6.595e-07 0.0121
ZNF610|162963 -0.2249 6.608e-07 0.0121
KDM5D|8284 -0.248 8.594e-07 0.0157

Figure S2.  Get High-res Image As an example, this figure shows the association of RANBP17|64901 to 'AGE'. P value = 1.39e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

216 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 167
  MALE 313
     
  Significant markers N = 216
  Higher in MALE 134
  Higher in FEMALE 82
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 -43.08 3.603e-160 6.59e-156 0.982
PRKY|5616 37.98 1.52e-104 2.78e-100 0.9797
NLGN4Y|22829 34.69 2.124e-76 3.89e-72 0.9752
RPS4Y1|6192 35.02 2.133e-71 3.9e-67 0.9859
TSIX|9383 -23.71 3.977e-69 7.27e-65 0.9659
ZFY|7544 34.73 1.837e-65 3.36e-61 0.9783
DDX3Y|8653 30.27 1.611e-56 2.95e-52 0.9739
KDM5C|8242 -16.81 1.069e-48 1.96e-44 0.8949
NCRNA00183|554203 -16.02 1.752e-43 3.2e-39 0.8608
KDM5D|8284 24.55 1.134e-38 2.07e-34 0.9708

Figure S3.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 3.6e-160 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) 90.88 (18)
  Score N
  0 1
  70 1
  80 3
  90 12
  100 17
     
  Significant markers N = 0
Clinical variable #5: 'PATHOLOGY.T'

2625 genes related to 'PATHOLOGY.T'.

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

PATHOLOGY.T Mean (SD) 1.91 (0.97)
  N
  T1 238
  T2 60
  T3 171
  T4 11
     
  Significant markers N = 2625
  pos. correlated 1420
  neg. correlated 1205
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 -0.4024 4.14e-20 7.57e-16
FKBP11|51303 0.3887 9.19e-19 1.68e-14
TMEM150C|441027 -0.3833 3.014e-18 5.51e-14
FAM122A|116224 -0.3831 3.156e-18 5.77e-14
PLEKHA9|51054 0.3798 6.4e-18 1.17e-13
ZNF132|7691 -0.3759 1.465e-17 2.68e-13
ACADSB|36 -0.3725 3.046e-17 5.57e-13
PTPRB|5787 -0.372 3.375e-17 6.17e-13
FAM160A1|729830 -0.3714 3.816e-17 6.98e-13
ANKRD56|345079 -0.3711 4.375e-17 8e-13

Figure S4.  Get High-res Image As an example, this figure shows the association of NR3C2|4306 to 'PATHOLOGY.T'. P value = 4.14e-20 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 228
  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 -7.72 5.065e-09 9.26e-05 0.719
PITX2|5308 6.94 1.839e-07 0.00336 0.785
ATP6V1D|51382 -6.13 4.006e-07 0.00732 0.7495
HEMGN|55363 -5.93 8.15e-07 0.0149 0.7437
TMEM104|54868 5.94 2.491e-06 0.0455 0.8055

Figure S5.  Get High-res Image As an example, this figure shows the association of C11ORF34|349633 to 'PATHOLOGY.N'. P value = 5.07e-09 with T-test analysis.

Clinical variable #7: 'PATHOLOGICSPREAD(M)'

317 genes related to 'PATHOLOGICSPREAD(M)'.

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

PATHOLOGICSPREAD(M) Labels N
  M0 403
  M1 77
     
  Significant markers N = 317
  Higher in M1 264
  Higher in M0 53
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 -6.98 2.078e-10 3.8e-06 0.7458
IL20RB|53833 6.7 1.089e-09 1.99e-05 0.7308
PLEKHA9|51054 6.68 1.135e-09 2.08e-05 0.7383
C22ORF9|23313 6.61 1.462e-09 2.67e-05 0.735
BIRC5|332 6.63 1.615e-09 2.95e-05 0.7295
INHBE|83729 6.55 2.516e-09 4.6e-05 0.7275
NFE2L3|9603 6.48 2.544e-09 4.65e-05 0.7237
TYMP|1890 6.38 3.096e-09 5.66e-05 0.7102
OIP5|11339 6.38 4.433e-09 8.11e-05 0.7251
CENPA|1058 6.35 6.395e-09 0.000117 0.7237

Figure S6.  Get High-res Image As an example, this figure shows the association of GARNL3|84253 to 'PATHOLOGICSPREAD(M)'. P value = 2.08e-10 with T-test analysis.

Clinical variable #8: 'TUMOR.STAGE'

3057 genes related to 'TUMOR.STAGE'.

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

TUMOR.STAGE Mean (SD) 2.09 (1.2)
  N
  Stage 1 234
  Stage 2 48
  Stage 3 117
  Stage 4 81
     
  Significant markers N = 3057
  pos. correlated 1674
  neg. correlated 1383
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 0.4116 4.754e-21 8.7e-17
NR3C2|4306 -0.4073 1.329e-20 2.43e-16
FKBP11|51303 0.4063 1.655e-20 3.03e-16
FAM122A|116224 -0.3988 9.48e-20 1.73e-15
NOP2|4839 0.3897 7.358e-19 1.35e-14
TSPAN7|7102 -0.3858 1.741e-18 3.18e-14
ALDH6A1|4329 -0.385 2.071e-18 3.79e-14
ACADSB|36 -0.382 4.016e-18 7.34e-14
PTPRB|5787 -0.3796 6.725e-18 1.23e-13
FAM160A1|729830 -0.379 7.664e-18 1.4e-13

Figure S7.  Get High-res Image As an example, this figure shows the association of PLEKHA9|51054 to 'TUMOR.STAGE'. P value = 4.75e-21 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 = 480

  • Number of genes = 18295

  • 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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