Correlation between mRNAseq expression and clinical features
Lung Adenocarcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1DF6Q3K
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/C1DF6Q3K
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 18308 genes and 14 clinical features across 464 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 1 gene correlated to 'Time to Death'.

    • NGRN|51335

  • 66 genes correlated to 'AGE'.

    • AHRR|57491 ,  PLA1A|51365 ,  C11ORF84|144097 ,  GPR15|2838 ,  CYP1A1|1543 ,  ...

  • 47 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • FAM117A|81558 ,  CCL19|6363 ,  RASGRP2|10235 ,  DPYS|1807 ,  KIAA0748|9840 ,  ...

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

    • C14ORF139|79686 ,  RASGRP2|10235 ,  ST8SIA1|6489 ,  GP1BA|2811 ,  PTGDS|5730 ,  ...

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

    • ARID4A|5926 ,  RCOR3|55758 ,  DAPK2|23604 ,  EPM2AIP1|9852 ,  ACSS1|84532 ,  ...

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

    • C3ORF42|84657 ,  PLEKHH2|130271 ,  MACF1|23499 ,  ZNF589|51385 ,  DCTN2|10540 ,  ...

  • 169 genes correlated to 'GENDER'.

    • HDHD1A|8226 ,  NCRNA00183|554203 ,  CYORF15B|84663 ,  CYORF15A|246126 ,  NDUFS1|4719 ,  ...

  • 1 gene correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • SLC24A6|80024

  • 35 genes correlated to 'HISTOLOGICAL.TYPE'.

    • KCNQ1|3784 ,  MECOM|2122 ,  ZNF33B|7582 ,  SPHK1|8877 ,  EPR1|8475 ,  ...

  • 3 genes correlated to 'NUMBERPACKYEARSSMOKED'.

    • TAF7L|54457 ,  C5ORF33|133686 ,  MED24|9862

  • 2 genes correlated to 'RACE'.

    • CRYBB2|1415 ,  GSTT2|2953

  • No genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION', 'COMPLETENESS.OF.RESECTION', 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=1 shorter survival N=1 longer survival N=0
AGE Spearman correlation test N=66 older N=32 younger N=34
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=47        
PATHOLOGY T STAGE Spearman correlation test N=252 higher stage N=17 lower stage N=235
PATHOLOGY N STAGE Spearman correlation test N=50 higher stage N=16 lower stage N=34
PATHOLOGY M STAGE Kruskal-Wallis test N=51        
GENDER Wilcoxon test N=169 male N=169 female N=0
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=1 higher score N=1 lower score N=0
HISTOLOGICAL TYPE Kruskal-Wallis test N=35        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test N=3 higher numberpackyearssmoked N=3 lower numberpackyearssmoked N=0
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test N=2        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'Time to Death'

One gene related to 'Time to Death'.

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

Time to Death Duration (Years) 1-2696 (median=477)
  censored N = 321
  death N = 84
     
  Significant markers N = 1
  associated with shorter survival 1
  associated with longer survival 0
List of one gene differentially expressed by 'Time to Death'

Table S2.  Get Full Table List of one gene significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
NGRN|51335 2.9 4.8e-06 0.088 0.664
Clinical variable #2: 'AGE'

66 genes related to 'AGE'.

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

AGE Mean (SD) 65.62 (9.7)
  Significant markers N = 66
  pos. correlated 32
  neg. correlated 34
List of top 10 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
AHRR|57491 -0.2604 3.999e-08 0.000732
PLA1A|51365 0.2569 5.881e-08 0.00108
C11ORF84|144097 -0.2509 1.216e-07 0.00223
GPR15|2838 -0.2574 1.444e-07 0.00264
CYP1A1|1543 -0.3038 1.869e-07 0.00342
C9ORF140|89958 -0.2463 2.105e-07 0.00385
C7ORF68|29923 -0.2409 3.897e-07 0.00713
METTL7B|196410 0.2407 4.016e-07 0.00735
EDA2R|60401 0.2406 4.029e-07 0.00737
THRB|7068 0.2396 4.52e-07 0.00827
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

47 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S5.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 4
  STAGE IA 113
  STAGE IB 132
  STAGE IIA 43
  STAGE IIB 68
  STAGE IIIA 69
  STAGE IIIB 11
  STAGE IV 23
     
  Significant markers N = 47
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

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

ANOVA_P Q
FAM117A|81558 2.473e-07 0.00453
CCL19|6363 2.782e-07 0.00509
RASGRP2|10235 3.302e-07 0.00604
DPYS|1807 3.746e-07 0.00686
KIAA0748|9840 6.641e-07 0.0122
RBP5|83758 6.819e-07 0.0125
PTGDS|5730 7.737e-07 0.0142
ZNF540|163255 7.767e-07 0.0142
FAM125B|89853 1.218e-06 0.0223
CD40LG|959 1.306e-06 0.0239
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 1.86 (0.73)
  N
  1 143
  2 260
  3 41
  4 18
     
  Significant markers N = 252
  pos. correlated 17
  neg. correlated 235
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S8.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
C14ORF139|79686 -0.2819 6.943e-10 1.27e-05
RASGRP2|10235 -0.2704 3.486e-09 6.38e-05
ST8SIA1|6489 -0.2696 3.911e-09 7.16e-05
GP1BA|2811 -0.272 4.153e-09 7.6e-05
PTGDS|5730 -0.2679 4.949e-09 9.06e-05
CCL19|6363 -0.2676 5.334e-09 9.76e-05
FAM125B|89853 -0.2663 6.103e-09 0.000112
MS4A1|931 -0.263 9.857e-09 0.00018
MAL|4118 -0.261 1.249e-08 0.000229
MAP4K1|11184 -0.2606 1.305e-08 0.000239
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

Table S9.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.52 (0.77)
  N
  0 293
  1 88
  2 71
  3 2
     
  Significant markers N = 50
  pos. correlated 16
  neg. correlated 34
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
ARID4A|5926 -0.2557 3.274e-08 0.000599
RCOR3|55758 -0.2387 2.663e-07 0.00488
DAPK2|23604 -0.2355 3.863e-07 0.00707
EPM2AIP1|9852 -0.2282 8.973e-07 0.0164
ACSS1|84532 -0.2271 1.006e-06 0.0184
TOX|9760 -0.2269 1.037e-06 0.019
SULT2B1|6820 0.224 1.424e-06 0.0261
ZNF483|158399 -0.2227 1.657e-06 0.0303
MASP2|10747 -0.2228 1.677e-06 0.0307
FAM117A|81558 -0.2221 1.767e-06 0.0323
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

Table S11.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 319
  M1 18
  M1A 1
  M1B 3
  MX 119
     
  Significant markers N = 51
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
C3ORF42|84657 2.897e-08 0.00053
PLEKHH2|130271 4.99e-08 0.000914
MACF1|23499 8.757e-08 0.0016
ZNF589|51385 2.473e-07 0.00453
DCTN2|10540 2.773e-07 0.00508
TRUB2|26995 4.201e-07 0.00769
BSN|8927 8.077e-07 0.0148
RBM33|155435 9.163e-07 0.0168
PRDX3|10935 1.048e-06 0.0192
MRPS11|64963 1.153e-06 0.0211
Clinical variable #7: 'GENDER'

169 genes related to 'GENDER'.

Table S13.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 252
  MALE 212
     
  Significant markers N = 169
  Higher in MALE 169
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S14.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 40 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HDHD1A|8226 13387 3.423e-20 6.26e-16 0.7482
NCRNA00183|554203 13991 9.489e-19 1.74e-14 0.7381
CYORF15B|84663 6339 1.354e-18 2.48e-14 0.9967
CYORF15A|246126 6314 2.513e-18 4.6e-14 0.9928
NDUFS1|4719 36188 4.529e-11 8.28e-07 0.6774
LRRC55|219527 17345 2.543e-09 4.65e-05 0.6621
RTN4R|65078 18232 3.783e-09 6.91e-05 0.6587
DARS2|55157 35076 6.144e-09 0.000112 0.6566
RNF175|285533 18135.5 6.929e-09 0.000127 0.6564
GLYATL2|219970 8508.5 8.386e-09 0.000153 0.6845
Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

One gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S15.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 83.9 (23)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene differentially expressed by 'KARNOFSKY.PERFORMANCE.SCORE'

Table S16.  Get Full Table List of one gene significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
SLC24A6|80024 0.4677 9.416e-06 0.172
Clinical variable #9: 'HISTOLOGICAL.TYPE'

35 genes related to 'HISTOLOGICAL.TYPE'.

Table S17.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  LUNG ACINAR ADENOCARCINOMA 15
  LUNG ADENOCARCINOMA MIXED SUBTYPE 93
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 293
  LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS 4
  LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS 19
  LUNG CLEAR CELL ADENOCARCINOMA 2
  LUNG MICROPAPILLARY ADENOCARCINOMA 4
  LUNG MUCINOUS ADENOCARCINOMA 2
  LUNG PAPILLARY ADENOCARCINOMA 19
  LUNG SIGNET RING ADENOCARCINOMA 1
  LUNG SOLID PATTERN PREDOMINANT ADENOCARCINOMA 5
  MUCINOUS (COLLOID) CARCINOMA 7
     
  Significant markers N = 35
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
KCNQ1|3784 1.033e-07 0.00189
MECOM|2122 7.875e-07 0.0144
ZNF33B|7582 1.708e-06 0.0313
SPHK1|8877 1.915e-06 0.0351
EPR1|8475 2.383e-06 0.0436
CCNE2|9134 2.57e-06 0.047
BIRC5|332 3.214e-06 0.0588
NR3C2|4306 3.268e-06 0.0598
THOC4|10189 3.9e-06 0.0714
FAM54A|113115 3.996e-06 0.0731
Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S19.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 21
  YES 443
     
  Significant markers N = 0
Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

3 genes related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 41.9 (27)
  Significant markers N = 3
  pos. correlated 3
  neg. correlated 0
List of 3 genes differentially expressed by 'NUMBERPACKYEARSSMOKED'

Table S21.  Get Full Table List of 3 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
TAF7L|54457 0.2672 6.759e-06 0.124
C5ORF33|133686 0.2476 8.717e-06 0.16
MED24|9862 0.2439 1.199e-05 0.219
Clinical variable #12: 'COMPLETENESS.OF.RESECTION'

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

Table S22.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 318
  R1 11
  R2 4
  RX 19
     
  Significant markers N = 0
Clinical variable #13: 'RACE'

2 genes related to 'RACE'.

Table S23.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 7
  BLACK OR AFRICAN AMERICAN 27
  WHITE 362
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'RACE'

Table S24.  Get Full Table List of 2 genes differentially expressed by 'RACE'

ANOVA_P Q
CRYBB2|1415 2.143e-07 0.00392
GSTT2|2953 1.544e-05 0.283
Clinical variable #14: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S25.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 7
  NOT HISPANIC OR LATINO 333
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 464

  • Number of genes = 18308

  • 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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