Correlation between mRNAseq 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/C1QN65N0
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/C1QN65N0
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 18514 genes and 14 clinical features across 419 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 8 clinical features related to at least one genes.

  • 33 genes correlated to 'AGE'.

    • PRSS12|8492 ,  GLB1L|79411 ,  GLI3|2737 ,  EYA2|2139 ,  NWD1|284434 ,  ...

  • 13 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • CENPE|1062 ,  CA4|762 ,  C9ORF152|401546 ,  ANLN|54443 ,  TCOF1|6949 ,  ...

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

    • SFTPC|6440 ,  KLF15|28999 ,  AGER|177 ,  C8ORF46|254778 ,  RAB11FIP4|84440 ,  ...

  • 1 gene correlated to 'PATHOLOGY.N.STAGE'.

    • KPNA2|3838

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

    • PPIAL4G|644591 ,  CKS1B|1163 ,  MLL2|8085 ,  POLE3|54107 ,  ZC3H13|23091 ,  ...

  • 34 genes correlated to 'GENDER'.

    • CYORF15A|246126 ,  CYORF15B|84663 ,  HDHD1A|8226 ,  SCP2|6342 ,  CLEC10A|10462 ,  ...

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

    • C16ORF79|283870 ,  PPIAL4G|644591 ,  SULT1A3|6818 ,  LOC90834|90834 ,  LUC7L3|51747 ,  ...

  • 1 gene correlated to 'COMPLETENESS.OF.RESECTION'.

    • LYRM4|57128

  • No genes correlated to 'Time to Death', 'HISTOLOGICAL.TYPE', 'RADIATIONS.RADIATION.REGIMENINDICATION', 'NUMBERPACKYEARSSMOKED', '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=33 older N=30 younger N=3
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=13        
PATHOLOGY T STAGE Spearman correlation test N=10 higher stage N=0 lower stage N=10
PATHOLOGY N STAGE Spearman correlation test N=1 higher stage N=1 lower stage N=0
PATHOLOGY M STAGE Kruskal-Wallis test N=9        
GENDER Wilcoxon test N=34 male N=34 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=34 higher score N=31 lower score N=3
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=1        
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=640)
  censored N = 266
  death N = 120
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

33 genes related to 'AGE'.

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

AGE Mean (SD) 67.13 (8.6)
  Significant markers N = 33
  pos. correlated 30
  neg. correlated 3
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
PRSS12|8492 0.2779 1.046e-08 0.000194
GLB1L|79411 0.2682 3.342e-08 0.000619
GLI3|2737 0.2616 7.355e-08 0.00136
EYA2|2139 0.2395 9.288e-07 0.0172
NWD1|284434 0.2395 1.268e-06 0.0235
NSUN5|55695 -0.2308 2.26e-06 0.0418
WDR63|126820 0.2345 2.593e-06 0.048
PARM1|25849 0.2283 2.919e-06 0.054
LRRIQ1|84125 0.2288 3.676e-06 0.068
C6|729 0.2434 3.706e-06 0.0686
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

13 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 73
  STAGE IB 136
  STAGE II 1
  STAGE IIA 52
  STAGE IIB 70
  STAGE IIIA 57
  STAGE IIIB 19
  STAGE IV 6
     
  Significant markers N = 13
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
CENPE|1062 1.924e-07 0.00356
CA4|762 8.322e-07 0.0154
C9ORF152|401546 1.947e-06 0.036
ANLN|54443 5.914e-06 0.109
TCOF1|6949 7.652e-06 0.142
KIT|3815 8.396e-06 0.155
MKI67|4288 8.835e-06 0.164
CLDN18|51208 9.491e-06 0.176
RPTOR|57521 1.083e-05 0.2
CYB5A|1528 1.155e-05 0.214
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 1.97 (0.73)
  N
  1 100
  2 252
  3 48
  4 19
     
  Significant markers N = 10
  pos. correlated 0
  neg. correlated 10
List of 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S7.  Get Full Table List of 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
SFTPC|6440 -0.2494 2.938e-07 0.00544
KLF15|28999 -0.23 1.962e-06 0.0363
AGER|177 -0.2276 2.509e-06 0.0465
C8ORF46|254778 -0.2268 4.719e-06 0.0874
RAB11FIP4|84440 -0.2214 4.772e-06 0.0883
CNR1|1268 -0.2227 4.899e-06 0.0907
GDF10|2662 -0.2247 5.24e-06 0.097
KLB|152831 -0.2131 1.32e-05 0.244
FLJ10038|55056 -0.2098 1.489e-05 0.276
DMRTC1B|728656 -0.2211 1.595e-05 0.295
Clinical variable #5: 'PATHOLOGY.N.STAGE'

One gene related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE Mean (SD) 0.47 (0.7)
  N
  0 262
  1 111
  2 35
  3 5
     
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene differentially expressed by 'PATHOLOGY.N.STAGE'

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

SpearmanCorr corrP Q
KPNA2|3838 0.2257 3.599e-06 0.0666
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 357
  M1 5
  M1A 1
  MX 50
     
  Significant markers N = 9
List of 9 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of 9 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
PPIAL4G|644591 1.464e-07 0.00271
CKS1B|1163 1.003e-06 0.0186
MLL2|8085 3.125e-06 0.0578
POLE3|54107 4.24e-06 0.0785
ZC3H13|23091 8.333e-06 0.154
C12ORF41|54934 1.398e-05 0.259
SNX11|29916 1.437e-05 0.266
COQ5|84274 1.472e-05 0.272
MRPL50|54534 1.496e-05 0.277
Clinical variable #7: 'GENDER'

34 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 107
  MALE 312
     
  Significant markers N = 34
  Higher in MALE 34
  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'. 38 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
CYORF15A|246126 7783 1.199e-16 2.22e-12 0.9978
CYORF15B|84663 4968 2.38e-11 4.4e-07 0.9952
HDHD1A|8226 9643 8.622e-11 1.59e-06 0.7102
SCP2|6342 10693 2.868e-08 0.00053 0.6797
CLEC10A|10462 10860 6.859e-08 0.00127 0.6747
LRRC41|10489 10942 1.044e-07 0.00193 0.6722
CXORF38|159013 11057 1.862e-07 0.00344 0.6688
HLA-DQB2|3120 11194 3.66e-07 0.00676 0.6647
PHC2|1912 11324 6.85e-07 0.0127 0.6608
YARS2|51067 22019 8.323e-07 0.0154 0.6596
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

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

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

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 52.58 (42)
  Significant markers N = 34
  pos. correlated 31
  neg. correlated 3
List of top 10 genes differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S15.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
C16ORF79|283870 0.5346 3.4e-08 0.000629
PPIAL4G|644591 -0.5265 5.947e-08 0.0011
SULT1A3|6818 0.5064 2.238e-07 0.00414
LOC90834|90834 0.5055 2.359e-07 0.00437
LUC7L3|51747 0.5012 3.098e-07 0.00573
NKTR|4820 0.4958 4.342e-07 0.00804
PLEKHM1P|440456 0.4901 6.152e-07 0.0114
LOC146880|146880 0.48 1.123e-06 0.0208
NPIPL3|23117 0.4788 1.207e-06 0.0223
FLJ10213|55096 0.4749 1.514e-06 0.028
Clinical variable #9: 'HISTOLOGICAL.TYPE'

No gene related to 'HISTOLOGICAL.TYPE'.

Table S16.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  LUNG BASALOID SQUAMOUS CELL CARCINOMA 12
  LUNG PAPILLARY SQUAMOUS CELL CARICNOMA 6
  LUNG SMALL CELL SQUAMOUS CELL CARCINOMA 1
  LUNG SQUAMOUS CELL CARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 400
     
  Significant markers N = 0
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S17.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 13
  YES 406
     
  Significant markers N = 0
Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 52.78 (31)
  Significant markers N = 0
Clinical variable #12: 'COMPLETENESS.OF.RESECTION'

One gene related to 'COMPLETENESS.OF.RESECTION'.

Table S19.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 341
  R1 8
  R2 4
  RX 18
     
  Significant markers N = 1
List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S20.  Get Full Table List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
LYRM4|57128 1.216e-05 0.225
Clinical variable #13: 'RACE'

No gene related to 'RACE'.

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

RACE Labels N
  ASIAN 9
  BLACK OR AFRICAN AMERICAN 16
  WHITE 297
     
  Significant markers N = 0
Clinical variable #14: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S22.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 8
  NOT HISPANIC OR LATINO 265
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 419

  • Number of genes = 18514

  • 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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