Correlation between mRNAseq expression and clinical features
Lung Adenocarcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C19C6W6C
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/C19C6W6C
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 458 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 3 genes correlated to 'Time to Death'.

    • NUDCD2|134492 ,  TMEM183A|92703 ,  HEATR5B|54497

  • 66 genes correlated to 'AGE'.

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

  • 39 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • FAM117A|81558 ,  RASGRP2|10235 ,  CCL19|6363 ,  DPYS|1807 ,  PTGDS|5730 ,  ...

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

    • C14ORF139|79686 ,  RASGRP2|10235 ,  GP1BA|2811 ,  PTGDS|5730 ,  FAM125B|89853 ,  ...

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

    • ARID4A|5926 ,  DAPK2|23604 ,  RCOR3|55758 ,  ZNF483|158399 ,  EPM2AIP1|9852 ,  ...

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

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

  • 184 genes correlated to 'GENDER'.

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

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

    • SLC24A6|80024

  • 22 genes correlated to 'HISTOLOGICAL.TYPE'.

    • KCNQ1|3784 ,  MECOM|2122 ,  SPHK1|8877 ,  ZNF33B|7582 ,  GINS2|51659 ,  ...

  • 4 genes correlated to 'NUMBERPACKYEARSSMOKED'.

    • C5ORF33|133686 ,  MTMR10|54893 ,  MED24|9862 ,  TAF7L|54457

  • 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=3 shorter survival N=2 longer survival N=1
AGE Spearman correlation test N=66 older N=31 younger N=35
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=39        
PATHOLOGY T STAGE Spearman correlation test N=213 higher stage N=18 lower stage N=195
PATHOLOGY N STAGE Spearman correlation test N=43 higher stage N=13 lower stage N=30
PATHOLOGY M STAGE Kruskal-Wallis test N=52        
GENDER Wilcoxon test N=184 male N=184 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=22        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test N=4 higher numberpackyearssmoked N=3 lower numberpackyearssmoked N=1
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'

3 genes related to 'Time to Death'.

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

Time to Death Duration (Years) 1-2696 (median=459)
  censored N = 319
  death N = 80
     
  Significant markers N = 3
  associated with shorter survival 2
  associated with longer survival 1
List of 3 genes differentially expressed by 'Time to Death'

Table S2.  Get Full Table List of 3 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
NUDCD2|134492 2.5 8.964e-06 0.16 0.7
TMEM183A|92703 2.4 1.027e-05 0.19 0.619
HEATR5B|54497 0.37 1.454e-05 0.27 0.349
Clinical variable #2: 'AGE'

66 genes related to 'AGE'.

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

AGE Mean (SD) 65.58 (9.7)
  Significant markers N = 66
  pos. correlated 31
  neg. correlated 35
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 -0.2656 2.618e-08 0.000479
PLA1A|51365 0.2565 7.688e-08 0.00141
GPR15|2838 -0.2605 1.256e-07 0.0023
CYP1A1|1543 -0.3085 1.446e-07 0.00265
C11ORF84|144097 -0.251 1.478e-07 0.00271
EDA2R|60401 0.246 2.644e-07 0.00484
C9ORF140|89958 -0.2458 2.702e-07 0.00494
METTL7B|196410 0.2442 3.232e-07 0.00591
C7ORF68|29923 -0.2429 3.754e-07 0.00687
THRB|7068 0.2398 5.344e-07 0.00978
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

39 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 4
  STAGE IA 111
  STAGE IB 132
  STAGE IIA 40
  STAGE IIB 68
  STAGE IIIA 68
  STAGE IIIB 11
  STAGE IV 23
     
  Significant markers N = 39
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 4.71e-07 0.00862
RASGRP2|10235 5.371e-07 0.00983
CCL19|6363 5.472e-07 0.01
DPYS|1807 5.878e-07 0.0108
PTGDS|5730 1.237e-06 0.0226
RBP5|83758 1.387e-06 0.0254
ZNF540|163255 1.6e-06 0.0293
KIAA0748|9840 1.638e-06 0.03
STAP1|26228 1.665e-06 0.0305
CNR1|1268 1.686e-06 0.0308
Clinical variable #4: 'PATHOLOGY.T.STAGE'

213 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
  1 141
  2 256
  3 41
  4 18
     
  Significant markers N = 213
  pos. correlated 18
  neg. correlated 195
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 -0.2796 1.229e-09 2.25e-05
RASGRP2|10235 -0.2678 6.237e-09 0.000114
GP1BA|2811 -0.2705 6.426e-09 0.000118
PTGDS|5730 -0.2658 8.151e-09 0.000149
FAM125B|89853 -0.2655 8.537e-09 0.000156
ST8SIA1|6489 -0.2653 8.808e-09 0.000161
CCL19|6363 -0.2631 1.216e-08 0.000223
MS4A1|931 -0.2609 1.627e-08 0.000298
MAP4K1|11184 -0.2584 2.161e-08 0.000396
MAL|4118 -0.2579 2.299e-08 0.000421
Clinical variable #5: 'PATHOLOGY.N.STAGE'

43 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
  0 291
  1 85
  2 70
  3 2
     
  Significant markers N = 43
  pos. correlated 13
  neg. correlated 30
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 -0.2448 1.553e-07 0.00284
DAPK2|23604 -0.2428 1.969e-07 0.0036
RCOR3|55758 -0.2381 3.407e-07 0.00624
ZNF483|158399 -0.2283 1.043e-06 0.0191
EPM2AIP1|9852 -0.2238 1.714e-06 0.0314
MASP2|10747 -0.2236 1.807e-06 0.0331
ACSS1|84532 -0.2228 1.918e-06 0.0351
LRRC37A2|474170 -0.2209 2.357e-06 0.0431
SULT2B1|6820 0.2201 2.567e-06 0.047
RARS|5917 0.218 3.191e-06 0.0584
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 314
  M1 18
  M1A 1
  M1B 3
  MX 118
     
  Significant markers N = 52
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 3.23e-08 0.000591
PLEKHH2|130271 7.808e-08 0.00143
MACF1|23499 1.656e-07 0.00303
DCTN2|10540 2.386e-07 0.00437
ZNF589|51385 2.903e-07 0.00531
TRUB2|26995 4.735e-07 0.00867
MRPS11|64963 7.1e-07 0.013
RBM33|155435 9.29e-07 0.017
PRDX3|10935 9.416e-07 0.0172
MAD2L1BP|9587 1.001e-06 0.0183
Clinical variable #7: 'GENDER'

184 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 249
  MALE 209
     
  Significant markers N = 184
  Higher in MALE 184
  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 13001 4.673e-20 8.55e-16 0.749
CYORF15B|84663 6250 1.43e-18 2.61e-14 0.9968
CYORF15A|246126 6224 2.742e-18 5.01e-14 0.9927
NCRNA00183|554203 13721 2.85e-18 5.21e-14 0.7363
NDUFS1|4719 35364 3.541e-11 6.47e-07 0.6795
RTN4R|65078 17517 1.673e-09 3.06e-05 0.6634
HLA-DQB2|3120 17626 2.69e-09 4.92e-05 0.6613
LRRC55|219527 17074 4.902e-09 8.96e-05 0.66
CLEC4F|165530 15050 4.943e-09 9.03e-05 0.6647
GLYATL2|219970 8237.5 6.665e-09 0.000122 0.6869
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) 83.7 (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 0.4598 1.573e-05 0.288
Clinical variable #9: 'HISTOLOGICAL.TYPE'

22 genes related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  LUNG ACINAR ADENOCARCINOMA 13
  LUNG ADENOCARCINOMA MIXED SUBTYPE 93
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 290
  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 4
  MUCINOUS (COLLOID) CARCINOMA 7
     
  Significant markers N = 22
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 1.458e-07 0.00267
MECOM|2122 1.332e-06 0.0244
SPHK1|8877 2.219e-06 0.0406
ZNF33B|7582 2.988e-06 0.0547
GINS2|51659 4.151e-06 0.076
NR3C2|4306 4.645e-06 0.085
CCNE2|9134 5.329e-06 0.0975
FAM54A|113115 5.447e-06 0.0997
BIRC5|332 5.471e-06 0.1
EPR1|8475 5.468e-06 0.1
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 437
     
  Significant markers N = 0
Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

4 genes related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 42.05 (27)
  Significant markers N = 4
  pos. correlated 3
  neg. correlated 1
List of 4 genes differentially expressed by 'NUMBERPACKYEARSSMOKED'

Table S21.  Get Full Table List of 4 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
C5ORF33|133686 0.2525 6.564e-06 0.12
MTMR10|54893 -0.2499 8.164e-06 0.149
MED24|9862 0.2448 1.263e-05 0.231
TAF7L|54457 0.2583 1.61e-05 0.295
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 316
  R1 11
  R2 4
  RX 17
     
  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 26
  WHITE 357
     
  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 5.017e-07 0.00918
GSTT2|2953 8.84e-06 0.162
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 328
     
  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 = 458

  • 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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