Correlation between RPPA expression and clinical features
Lung Squamous Cell Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1028QDV
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between RPPA expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1028QDV
Overview
Introduction

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

Summary

Testing the association between 174 genes and 14 clinical features across 195 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 5 clinical features related to at least one genes.

  • 10 genes correlated to 'AGE'.

    • PCNA|PCNA-M-V ,  RAD51|RAD51-M-C ,  CCNE1|CYCLIN_E1-M-V ,  AKT1S1|PRAS40_PT246-R-V ,  WWTR1|TAZ_PS89-R-C ,  ...

  • 2 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • RPS6|S6_PS235_S236-R-V ,  MAPK1 MAPK3|MAPK_PT202_Y204-R-V

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

    • BID|BID-R-C ,  CD49|CD49B-M-V ,  DVL3|DVL3-R-V ,  IRS1|IRS1-R-V ,  FN1|FIBRONECTIN-R-C ,  ...

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

    • MAPK1 MAPK3|MAPK_PT202_Y204-R-V ,  STAT3|STAT3_PY705-R-V ,  RPS6|S6_PS235_S236-R-V ,  MAP2K1|MEK1_PS217_S221-R-V

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

    • CDC2|CDK1-R-V ,  FOXO3|FOXO3A-R-C

  • No genes correlated to 'Time to Death', 'PATHOLOGY.M.STAGE', 'GENDER', 'HISTOLOGICAL.TYPE', 'RADIATIONS.RADIATION.REGIMENINDICATION', 'NUMBERPACKYEARSSMOKED', 'COMPLETENESS.OF.RESECTION', 'RACE', 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=10 older N=6 younger N=4
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=2        
PATHOLOGY T STAGE Spearman correlation test N=8 higher stage N=7 lower stage N=1
PATHOLOGY N STAGE Spearman correlation test N=4 higher stage N=0 lower stage N=4
PATHOLOGY M STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test   N=0        
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=2 higher score N=1 lower score N=1
HISTOLOGICAL TYPE Kruskal-Wallis test   N=0        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test   N=0        
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) 1-5287 (median=833)
  censored N = 111
  death N = 70
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

10 genes related to 'AGE'.

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

AGE Mean (SD) 67.41 (9.5)
  Significant markers N = 10
  pos. correlated 6
  neg. correlated 4
List of 10 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
PCNA|PCNA-M-V -0.3209 7.564e-06 0.00132
RAD51|RAD51-M-C -0.2743 0.0001453 0.0251
CCNE1|CYCLIN_E1-M-V -0.2539 0.0004545 0.0782
AKT1S1|PRAS40_PT246-R-V 0.2532 0.0004724 0.0808
WWTR1|TAZ_PS89-R-C -0.2509 0.0005325 0.0905
AKT1 AKT2 AKT3|AKT_PS473-R-V 0.249 0.0005899 0.0997
ERBB2|HER2_PY1248-R-V 0.2436 0.000782 0.131
GAB2|GAB2-R-V 0.2417 0.0008595 0.144
SRC|SRC_PY416-R-C 0.2393 0.0009739 0.162
BAD|BAD_PS112-R-V 0.2356 0.001173 0.194
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

2 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 1
  STAGE IA 28
  STAGE IB 71
  STAGE II 1
  STAGE IIA 23
  STAGE IIB 33
  STAGE IIIA 22
  STAGE IIIB 14
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of 2 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
RPS6|S6_PS235_S236-R-V 0.0001475 0.0257
MAPK1 MAPK3|MAPK_PT202_Y204-R-V 0.001054 0.182
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 1.98 (0.75)
  N
  1 45
  2 119
  3 20
  4 11
     
  Significant markers N = 8
  pos. correlated 7
  neg. correlated 1
List of 8 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7.  Get Full Table List of 8 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
BID|BID-R-C 0.2933 3.171e-05 0.00552
CD49|CD49B-M-V 0.2632 0.0002011 0.0348
DVL3|DVL3-R-V 0.2591 0.0002552 0.0439
IRS1|IRS1-R-V 0.2566 0.0002927 0.0501
FN1|FIBRONECTIN-R-C 0.2437 0.0005977 0.102
KDR|VEGFR2-R-V 0.2409 0.0006912 0.117
FRAP1|MTOR_PS2448-R-C -0.237 0.0008496 0.143
HSPA1A|HSP70-R-C 0.2348 0.0009528 0.159
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.48 (0.74)
  N
  0 124
  1 49
  2 16
  3 4
     
  Significant markers N = 4
  pos. correlated 0
  neg. correlated 4
List of 4 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of 4 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MAPK1 MAPK3|MAPK_PT202_Y204-R-V -0.3132 9.235e-06 0.00161
STAT3|STAT3_PY705-R-V -0.2818 7.188e-05 0.0124
RPS6|S6_PS235_S236-R-V -0.2661 0.0001841 0.0317
MAP2K1|MEK1_PS217_S221-R-V -0.2351 0.0009964 0.17
Clinical variable #6: 'PATHOLOGY.M.STAGE'

No gene related to 'PATHOLOGY.M.STAGE'.

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

PATHOLOGY.M.STAGE Labels N
  M0 176
  MX 16
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

No gene related to 'GENDER'.

Table S11.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 49
  MALE 146
     
  Significant markers N = 0
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

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

Table S12.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 30.29 (39)
  Significant markers N = 2
  pos. correlated 1
  neg. correlated 1
List of 2 genes differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S13.  Get Full Table List of 2 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
CDC2|CDK1-R-V -0.55 0.0007518 0.131
FOXO3|FOXO3A-R-C 0.5175 0.001724 0.298
Clinical variable #9: 'HISTOLOGICAL.TYPE'

No gene related to 'HISTOLOGICAL.TYPE'.

Table S14.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  LUNG BASALOID SQUAMOUS CELL CARCINOMA 3
  LUNG PAPILLARY SQUAMOUS CELL CARICNOMA 2
  LUNG SQUAMOUS CELL CARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 190
     
  Significant markers N = 0
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

No gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S15.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 10
  YES 185
     
  Significant markers N = 0
Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 51.69 (32)
  Significant markers N = 0
Clinical variable #12: 'COMPLETENESS.OF.RESECTION'

No gene related to 'COMPLETENESS.OF.RESECTION'.

Table S17.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 149
  R1 4
  R2 4
  RX 9
     
  Significant markers N = 0
Clinical variable #13: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 3
  BLACK OR AFRICAN AMERICAN 9
  WHITE 147
     
  Significant markers N = 0
Clinical variable #14: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 4
  NOT HISPANIC OR LATINO 120
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 195

  • Number of genes = 174

  • Number of clinical features = 14

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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