Correlation between RPPA expression and clinical features
Overview
Introduction

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

Summary

Testing the association between 189 genes and 12 clinical features across 158 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 9 clinical features related to at least one genes.

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

    • EIF4G1|EIF4G-R-C ,  DVL3|DVL3-R-V ,  EEF2K|EEF2K-R-V ,  RBM15|RBM15-R-V ,  XRCC5|KU80-R-C ,  ...

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

    • CDKN1B|P27_PT157-R-C ,  SQSTM1|P62-LCK-LIGAND-M-C

  • 6 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • STAT3|STAT3_PY705-R-V ,  RPS6|S6_PS235_S236-R-V ,  RPS6|S6_PS240_S244-R-V ,  MAPK1 MAPK3|MAPK_PT202_Y204-R-V ,  GSK3A GSK3B|GSK3-ALPHA-BETA_PS21_S9-R-V ,  ...

  • 2 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • CDKN1B|P27_PT157-R-C ,  SQSTM1|P62-LCK-LIGAND-M-C

  • 15 genes correlated to 'GLEASON_SCORE_COMBINED'.

    • SHC1|SHC_PY317-R-E ,  BCL2L11|BIM-R-V ,  TFRC|TFRC-R-V ,  GAB2|GAB2-R-V ,  CDH3|P-CADHERIN-R-C ,  ...

  • 27 genes correlated to 'GLEASON_SCORE_PRIMARY'.

    • EIF4G1|EIF4G-R-C ,  CCNB1|CYCLIN_B1-R-V ,  CAV1|CAVEOLIN-1-R-V ,  TFRC|TFRC-R-V ,  ERRFI1|MIG-6-M-V ,  ...

  • 5 genes correlated to 'GLEASON_SCORE_SECONDARY'.

    • CDH3|P-CADHERIN-R-C ,  ADAR|ADAR1-R-V ,  RPS6KB1|P70S6K_PT389-R-V ,  YWHAE|14-3-3_EPSILON-M-C ,  BCL2L11|BIM-R-V

  • 25 genes correlated to 'GLEASON_SCORE'.

    • BCL2L11|BIM-R-V ,  EIF4G1|EIF4G-R-C ,  GAB2|GAB2-R-V ,  TFRC|TFRC-R-V ,  SHC1|SHC_PY317-R-E ,  ...

  • 5 genes correlated to 'PSA_RESULT_PREOP'.

    • EEF2|EEF2-R-C ,  RAD50|RAD50-M-V ,  PRKAA1|AMPK_PT172-R-V ,  RAF1|C-RAF-R-V ,  ACACA|ACC1-R-E

  • No genes correlated to 'AGE', 'PSA_VALUE', and 'RACE'.

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
AGE Spearman correlation test   N=0        
PATHOLOGY T STAGE Spearman correlation test N=13 higher stage N=12 lower stage N=1
PATHOLOGY N STAGE Wilcoxon test N=2 class1 N=2 class0 N=0
COMPLETENESS OF RESECTION Kruskal-Wallis test N=6        
NUMBER OF LYMPH NODES Spearman correlation test N=2 higher number.of.lymph.nodes N=1 lower number.of.lymph.nodes N=1
GLEASON_SCORE_COMBINED Spearman correlation test N=15 higher score N=9 lower score N=6
GLEASON_SCORE_PRIMARY Spearman correlation test N=27 higher score N=11 lower score N=16
GLEASON_SCORE_SECONDARY Spearman correlation test N=5 higher score N=1 lower score N=4
GLEASON_SCORE Spearman correlation test N=25 higher score N=15 lower score N=10
PSA_RESULT_PREOP Spearman correlation test N=5 higher psa_result_preop N=5 lower psa_result_preop N=0
PSA_VALUE Spearman correlation test   N=0        
RACE Kruskal-Wallis test   N=0        
Clinical variable #1: 'AGE'

No gene related to 'AGE'.

Table S1.  Basic characteristics of clinical feature: 'AGE'

AGE Mean (SD) 60.6 (7.1)
  Significant markers N = 0
Clinical variable #2: 'PATHOLOGY.T.STAGE'

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

Table S2.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.66 (0.54)
  N
  2 58
  3 94
  4 5
     
  Significant markers N = 13
  pos. correlated 12
  neg. correlated 1
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S3.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
EIF4G1|EIF4G-R-C 0.3644 2.711e-06 0.000512
DVL3|DVL3-R-V 0.3539 5.433e-06 0.00102
EEF2K|EEF2K-R-V 0.3381 1.487e-05 0.00278
RBM15|RBM15-R-V 0.322 3.923e-05 0.0073
XRCC5|KU80-R-C 0.3177 5.015e-05 0.00928
GAB2|GAB2-R-V 0.2935 0.0001913 0.0352
TP53BP1|53BP1-R-E 0.2795 0.0003933 0.072
BRAF|B-RAF-M-C 0.2731 0.0005391 0.0981
NOTCH1|NOTCH1-R-V 0.2663 0.0007487 0.136
FOXO3|FOXO3A-R-C 0.2614 0.0009429 0.17
Clinical variable #3: 'PATHOLOGY.N.STAGE'

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

Table S4.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Labels N
  class0 123
  class1 17
     
  Significant markers N = 2
  Higher in class1 2
  Higher in class0 0
List of 2 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S5.  Get Full Table List of 2 genes differentially expressed by 'PATHOLOGY.N.STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
CDKN1B|P27_PT157-R-C 503.5 0.000551 0.104 0.7592
SQSTM1|P62-LCK-LIGAND-M-C 1559 0.001065 0.2 0.7456
Clinical variable #4: 'COMPLETENESS.OF.RESECTION'

6 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S6.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 111
  R1 33
  R2 1
  RX 4
     
  Significant markers N = 6
List of 6 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Clinical variable #5: 'NUMBER.OF.LYMPH.NODES'

2 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S8.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 0.22 (0.75)
  Value N
  0 123
  1 10
  2 3
  3 3
  6 1
     
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S9.  Get Full Table List of 2 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
CDKN1B|P27_PT157-R-C -0.2981 0.0003477 0.0657
SQSTM1|P62-LCK-LIGAND-M-C 0.2789 0.0008469 0.159
Clinical variable #6: 'GLEASON_SCORE_COMBINED'

15 genes related to 'GLEASON_SCORE_COMBINED'.

Table S10.  Basic characteristics of clinical feature: 'GLEASON_SCORE_COMBINED'

GLEASON_SCORE_COMBINED Mean (SD) 7.4 (0.87)
  Significant markers N = 15
  pos. correlated 9
  neg. correlated 6
List of top 10 genes differentially expressed by 'GLEASON_SCORE_COMBINED'

Table S11.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_COMBINED' by Spearman correlation test

SpearmanCorr corrP Q
SHC1|SHC_PY317-R-E -0.3648 2.448e-06 0.000463
BCL2L11|BIM-R-V 0.3487 7.137e-06 0.00134
TFRC|TFRC-R-V 0.3127 6.345e-05 0.0119
GAB2|GAB2-R-V 0.3019 0.0001158 0.0215
CDH3|P-CADHERIN-R-C -0.3008 0.0001231 0.0228
RPS6KB1|P70S6K_PT389-R-V -0.2936 0.0001807 0.0333
EGFR|EGFR_PY1068-R-C -0.2917 0.0001998 0.0366
EIF4G1|EIF4G-R-C 0.2787 0.0003906 0.0711
CAV1|CAVEOLIN-1-R-V -0.2662 0.0007241 0.131
PXN|PAXILLIN-R-C 0.2651 0.0007618 0.137
Clinical variable #7: 'GLEASON_SCORE_PRIMARY'

27 genes related to 'GLEASON_SCORE_PRIMARY'.

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

GLEASON_SCORE_PRIMARY Mean (SD) 3.54 (0.58)
  Score N
  2 1
  3 76
  4 75
  5 6
     
  Significant markers N = 27
  pos. correlated 11
  neg. correlated 16
List of top 10 genes differentially expressed by 'GLEASON_SCORE_PRIMARY'

Table S13.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE_PRIMARY' by Spearman correlation test

SpearmanCorr corrP Q
EIF4G1|EIF4G-R-C 0.3407 1.184e-05 0.00224
CCNB1|CYCLIN_B1-R-V 0.3249 3.115e-05 0.00586
CAV1|CAVEOLIN-1-R-V -0.3214 3.817e-05 0.00714
TFRC|TFRC-R-V 0.3189 4.424e-05 0.00823
ERRFI1|MIG-6-M-V 0.3188 4.468e-05 0.00827
GSK3A GSK3B|GSK3_PS9-R-V -0.3089 7.834e-05 0.0144
MAPK14|P38_PT180_Y182-R-V -0.3041 0.0001027 0.0188
ESR1|ER-ALPHA_PS118-R-V 0.2971 0.00015 0.0273
SQSTM1|P62-LCK-LIGAND-M-C 0.2871 0.0002546 0.0461
PRKCA |PKC-ALPHA_PS657-R-C -0.2851 0.0002819 0.0507
Clinical variable #8: 'GLEASON_SCORE_SECONDARY'

5 genes related to 'GLEASON_SCORE_SECONDARY'.

Table S14.  Basic characteristics of clinical feature: 'GLEASON_SCORE_SECONDARY'

GLEASON_SCORE_SECONDARY Mean (SD) 3.85 (0.68)
  Score N
  3 49
  4 83
  5 26
     
  Significant markers N = 5
  pos. correlated 1
  neg. correlated 4
List of 5 genes differentially expressed by 'GLEASON_SCORE_SECONDARY'

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

SpearmanCorr corrP Q
CDH3|P-CADHERIN-R-C -0.3161 5.199e-05 0.00983
ADAR|ADAR1-R-V -0.2907 0.0002109 0.0397
RPS6KB1|P70S6K_PT389-R-V -0.2872 0.0002538 0.0475
YWHAE|14-3-3_EPSILON-M-C -0.2641 0.0008005 0.149
BCL2L11|BIM-R-V 0.2509 0.001476 0.273
Clinical variable #9: 'GLEASON_SCORE'

25 genes related to 'GLEASON_SCORE'.

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

GLEASON_SCORE Mean (SD) 7.45 (0.91)
  Score N
  6 10
  7 100
  8 17
  9 29
  10 2
     
  Significant markers N = 25
  pos. correlated 15
  neg. correlated 10
List of top 10 genes differentially expressed by 'GLEASON_SCORE'

Table S17.  Get Full Table List of top 10 genes significantly correlated to 'GLEASON_SCORE' by Spearman correlation test

SpearmanCorr corrP Q
BCL2L11|BIM-R-V 0.3754 1.175e-06 0.000222
EIF4G1|EIF4G-R-C 0.3752 1.191e-06 0.000224
GAB2|GAB2-R-V 0.3557 4.502e-06 0.000842
TFRC|TFRC-R-V 0.3446 9.248e-06 0.00172
SHC1|SHC_PY317-R-E -0.3309 2.172e-05 0.00402
PXN|PAXILLIN-R-C 0.3231 3.461e-05 0.00637
DVL3|DVL3-R-V 0.3216 3.784e-05 0.00692
RBM15|RBM15-R-V 0.3112 6.876e-05 0.0125
RPS6KB1|P70S6K_PT389-R-V -0.3103 7.262e-05 0.0131
CCNB1|CYCLIN_B1-R-V 0.3039 0.0001038 0.0187
Clinical variable #10: 'PSA_RESULT_PREOP'

5 genes related to 'PSA_RESULT_PREOP'.

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

PSA_RESULT_PREOP Mean (SD) 11.27 (11)
  Significant markers N = 5
  pos. correlated 5
  neg. correlated 0
List of 5 genes differentially expressed by 'PSA_RESULT_PREOP'

Table S19.  Get Full Table List of 5 genes significantly correlated to 'PSA_RESULT_PREOP' by Spearman correlation test

SpearmanCorr corrP Q
EEF2|EEF2-R-C 0.3339 2.052e-05 0.00388
RAD50|RAD50-M-V 0.2811 0.0003785 0.0712
PRKAA1|AMPK_PT172-R-V 0.2645 0.0008486 0.159
RAF1|C-RAF-R-V 0.2629 0.0009135 0.17
ACACA|ACC1-R-E 0.2538 0.001386 0.256
Clinical variable #11: 'PSA_VALUE'

No gene related to 'PSA_VALUE'.

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

PSA_VALUE Mean (SD) 1.42 (4.5)
  Significant markers N = 0
Clinical variable #12: 'RACE'

No gene related to 'RACE'.

Table S21.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  ASIAN 2
  BLACK OR AFRICAN AMERICAN 6
  WHITE 121
     
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = PRAD-TP.rppa.txt

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

  • Number of patients = 158

  • Number of genes = 189

  • Number of clinical features = 12

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

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

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.

References
[1] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[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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