Correlation between mRNAseq expression and clinical features
Lung Adenocarcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1PR7TMH
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/C1PR7TMH
Overview
Introduction

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

Summary

Testing the association between 18308 genes and 13 clinical features across 457 samples, statistically thresholded by Q value < 0.05, 10 clinical features related to at least one genes.

  • 23 genes correlated to 'AGE'.

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

  • 7 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • FAM117A|81558 ,  ZNF540|163255 ,  PTGDS|5730 ,  CR2|1380 ,  NLRC3|197358 ,  ...

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

    • C14ORF139|79686 ,  FAM125B|89853 ,  GP1BA|2811 ,  RASGRP2|10235 ,  ST8SIA1|6489 ,  ...

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

    • DAPK2|23604 ,  ARID4A|5926 ,  RCOR3|55758 ,  ZNF483|158399 ,  ACSS1|84532 ,  ...

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

    • CUL4A|8451 ,  DCUN1D2|55208 ,  AMFR|267 ,  SLC35F2|54733 ,  TMCO3|55002 ,  ...

  • 107 genes correlated to 'GENDER'.

    • PRKY|5616 ,  ZFY|7544 ,  RPS4Y1|6192 ,  XIST|7503 ,  DDX3Y|8653 ,  ...

  • 37 genes correlated to 'HISTOLOGICAL.TYPE'.

    • A4GNT|51146 ,  CREB3L3|84699 ,  REG4|83998 ,  BTNL8|79908 ,  MIA|8190 ,  ...

  • 1 gene correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • PGAM2|5224

  • 3 genes correlated to 'YEAROFTOBACCOSMOKINGONSET'.

    • ANKRD33|341405 ,  HIST1H2BG|8339 ,  GPR15|2838

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

    • PAX2|5076

  • No genes correlated to 'Time to Death', 'KARNOFSKY.PERFORMANCE.SCORE', and 'NUMBERPACKYEARSSMOKED'.

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 Q value < 0.05.

Clinical feature Statistical test Significant genes Associated with                 Associated with
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=23 older N=11 younger N=12
NEOPLASM DISEASESTAGE ANOVA test N=7        
PATHOLOGY T STAGE Spearman correlation test N=89 higher stage N=3 lower stage N=86
PATHOLOGY N STAGE Spearman correlation test N=8 higher stage N=0 lower stage N=8
PATHOLOGY M STAGE ANOVA test N=55        
GENDER t test N=107 male N=36 female N=71
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
HISTOLOGICAL TYPE ANOVA test N=37        
RADIATIONS RADIATION REGIMENINDICATION t test N=1 yes N=1 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test N=3 higher yearoftobaccosmokingonset N=3 lower yearoftobaccosmokingonset N=0
COMPLETENESS OF RESECTION ANOVA test N=1        
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 (Months) 0-224 (median=13.2)
  censored N = 306
  death N = 119
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

23 genes related to 'AGE'.

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

AGE Mean (SD) 65.56 (9.7)
  Significant markers N = 23
  pos. correlated 11
  neg. correlated 12
List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

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

SpearmanCorr corrP Q
AHRR|57491 -0.2634 3.556e-08 0.000651
PLA1A|51365 0.2544 1.015e-07 0.00186
C11ORF84|144097 -0.2524 1.288e-07 0.00236
CYP1A1|1543 -0.3085 1.446e-07 0.00265
GPR15|2838 -0.2582 1.701e-07 0.00311
EDA2R|60401 0.2452 2.981e-07 0.00546
C9ORF140|89958 -0.2436 3.562e-07 0.00652
METTL7B|196410 0.2419 4.356e-07 0.00797
C7ORF68|29923 -0.2406 5.032e-07 0.00921
THRB|7068 0.2393 5.842e-07 0.0107

Figure S1.  Get High-res Image As an example, this figure shows the association of AHRR|57491 to 'AGE'. P value = 3.56e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

7 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 4
  STAGE IA 110
  STAGE IB 133
  STAGE IIA 41
  STAGE IIB 66
  STAGE IIIA 68
  STAGE IIIB 11
  STAGE IV 23
     
  Significant markers N = 7
List of 7 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of 7 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
FAM117A|81558 7.512e-08 0.00138
ZNF540|163255 2.08e-07 0.00381
PTGDS|5730 8.702e-07 0.0159
CR2|1380 1.001e-06 0.0183
NLRC3|197358 1.604e-06 0.0294
RBP5|83758 1.925e-06 0.0352
UCHL5|51377 2.641e-06 0.0483

Figure S2.  Get High-res Image As an example, this figure shows the association of FAM117A|81558 to 'NEOPLASM.DISEASESTAGE'. P value = 7.51e-08 with ANOVA analysis.

Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 1.86 (0.73)
  N
  1 140
  2 256
  3 41
  4 18
     
  Significant markers N = 89
  pos. correlated 3
  neg. correlated 86
List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

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

SpearmanCorr corrP Q
C14ORF139|79686 -0.2762 2.081e-09 3.81e-05
FAM125B|89853 -0.2684 5.973e-09 0.000109
GP1BA|2811 -0.2679 9.431e-09 0.000173
RASGRP2|10235 -0.2648 9.743e-09 0.000178
ST8SIA1|6489 -0.2628 1.263e-08 0.000231
PTGDS|5730 -0.2624 1.329e-08 0.000243
CCL19|6363 -0.2603 1.821e-08 0.000333
MS4A1|931 -0.2587 2.228e-08 0.000408
MAL|4118 -0.2562 2.984e-08 0.000546
PPP1R16B|26051 -0.2556 3.226e-08 0.00059

Figure S3.  Get High-res Image As an example, this figure shows the association of C14ORF139|79686 to 'PATHOLOGY.T.STAGE'. P value = 2.08e-09 with Spearman correlation analysis.

Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 0.52 (0.77)
  N
  0 290
  1 85
  2 70
  3 2
     
  Significant markers N = 8
  pos. correlated 0
  neg. correlated 8
List of 8 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S9.  Get Full Table List of 8 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
DAPK2|23604 -0.2446 1.635e-07 0.00299
ARID4A|5926 -0.2445 1.65e-07 0.00302
RCOR3|55758 -0.2382 3.47e-07 0.00635
ZNF483|158399 -0.2304 8.464e-07 0.0155
ACSS1|84532 -0.2242 1.681e-06 0.0308
MASP2|10747 -0.2225 2.075e-06 0.038
EPM2AIP1|9852 -0.2221 2.114e-06 0.0387
LRRC37A2|474170 -0.2212 2.331e-06 0.0427

Figure S4.  Get High-res Image As an example, this figure shows the association of DAPK2|23604 to 'PATHOLOGY.N.STAGE'. P value = 1.63e-07 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 313
  M1 18
  M1A 1
  M1B 3
  MX 118
     
  Significant markers N = 55
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
CUL4A|8451 1.514e-12 2.77e-08
DCUN1D2|55208 1.325e-09 2.43e-05
AMFR|267 2.032e-09 3.72e-05
SLC35F2|54733 2.099e-09 3.84e-05
TMCO3|55002 9.291e-09 0.00017
PROZ|8858 1.227e-08 0.000225
LAMP1|3916 1.241e-08 0.000227
SEZ6|124925 1.252e-08 0.000229
TFDP1|7027 1.371e-08 0.000251
PLEKHH2|130271 2.324e-08 0.000425

Figure S5.  Get High-res Image As an example, this figure shows the association of CUL4A|8451 to 'PATHOLOGY.M.STAGE'. P value = 1.51e-12 with ANOVA analysis.

Clinical variable #7: 'GENDER'

107 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 249
  MALE 208
     
  Significant markers N = 107
  Higher in MALE 36
  Higher in FEMALE 71
List of top 10 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
PRKY|5616 52.07 1.5e-181 2.75e-177 0.9997
ZFY|7544 63.24 4.158e-163 7.61e-159 0.9983
RPS4Y1|6192 57.69 2.78e-136 5.09e-132 0.9974
XIST|7503 -42.03 1.246e-116 2.28e-112 0.9802
DDX3Y|8653 59.4 7.034e-106 1.29e-101 0.9982
USP9Y|8287 52.41 9.992e-89 1.83e-84 0.9997
KDM5D|8284 52.07 4.957e-86 9.07e-82 0.9991
NLGN4Y|22829 30.6 6.389e-63 1.17e-58 0.9922
UTY|7404 38.94 4.725e-49 8.65e-45 0.9972
TSIX|9383 -19.54 1.468e-43 2.69e-39 0.9593

Figure S6.  Get High-res Image As an example, this figure shows the association of PRKY|5616 to 'GENDER'. P value = 1.5e-181 with T-test analysis.

Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

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

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 83.62 (23)
  Significant markers N = 0
Clinical variable #9: 'HISTOLOGICAL.TYPE'

37 genes related to 'HISTOLOGICAL.TYPE'.

Table S15.  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 18
  LUNG SIGNET RING ADENOCARCINOMA 1
  LUNG SOLID PATTERN PREDOMINANT ADENOCARCINOMA 4
  MUCINOUS (COLLOID) CARCINOMA 7
     
  Significant markers N = 37
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S16.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
A4GNT|51146 3.88e-12 7.1e-08
CREB3L3|84699 5.068e-12 9.28e-08
REG4|83998 4.258e-10 7.79e-06
BTNL8|79908 7.067e-10 1.29e-05
MIA|8190 1.527e-08 0.00028
MUC6|4588 1.592e-08 0.000291
DPCR1|135656 1.794e-08 0.000328
SPOCD1|90853 3.639e-08 0.000666
CHST5|23563 4.209e-08 0.00077
SOX10|6663 7.712e-08 0.00141

Figure S7.  Get High-res Image As an example, this figure shows the association of A4GNT|51146 to 'HISTOLOGICAL.TYPE'. P value = 3.88e-12 with ANOVA analysis.

Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

One gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 21
  YES 436
     
  Significant markers N = 1
  Higher in YES 1
  Higher in NO 0
List of one gene differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S18.  Get Full Table List of one gene differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
PGAM2|5224 6.43 5.966e-07 0.0109 0.7549

Figure S8.  Get High-res Image As an example, this figure shows the association of PGAM2|5224 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 5.97e-07 with T-test analysis.

Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 42.05 (27)
  Significant markers N = 0
Clinical variable #12: 'YEAROFTOBACCOSMOKINGONSET'

3 genes related to 'YEAROFTOBACCOSMOKINGONSET'.

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

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1964.9 (12)
  Significant markers N = 3
  pos. correlated 3
  neg. correlated 0
List of 3 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

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

SpearmanCorr corrP Q
ANKRD33|341405 0.3935 2.036e-07 0.00373
HIST1H2BG|8339 0.3115 1.105e-06 0.0202
GPR15|2838 0.3075 1.896e-06 0.0347

Figure S9.  Get High-res Image As an example, this figure shows the association of ANKRD33|341405 to 'YEAROFTOBACCOSMOKINGONSET'. P value = 2.04e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #13: 'COMPLETENESS.OF.RESECTION'

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

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

COMPLETENESS.OF.RESECTION Labels N
  R0 315
  R1 10
  R2 4
  RX 17
     
  Significant markers N = 1
List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S23.  Get Full Table List of one gene differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
PAX2|5076 8.82e-07 0.0161

Figure S10.  Get High-res Image As an example, this figure shows the association of PAX2|5076 to 'COMPLETENESS.OF.RESECTION'. P value = 8.82e-07 with ANOVA analysis.

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 = 457

  • Number of genes = 18308

  • Number of clinical features = 13

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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