Correlation between mRNAseq expression and clinical features
Lung Adenocarcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1M044G3
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1M044G3
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 18319 genes and 15 clinical features across 514 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 10 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • GPR15|2838 ,  SLC40A1|30061 ,  C9ORF140|89958 ,  C7ORF68|29923 ,  EDA2R|60401 ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • RASGRP2|10235 ,  FAM117A|81558 ,  PTGDS|5730 ,  RBP5|83758 ,  BLK|640 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

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

  • 30 genes correlated to 'PATHOLOGY_N_STAGE'.

    • ARID4A|5926 ,  RCOR3|55758 ,  ACSS1|84532 ,  FAM117A|81558 ,  RARS|5917 ,  ...

  • 4 genes correlated to 'GENDER'.

    • HDHD1A|8226 ,  NCRNA00183|554203 ,  CYORF15A|246126 ,  CYORF15B|84663

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • KCNQ1|3784 ,  ATAD5|79915 ,  CCNF|899 ,  MECOM|2122 ,  BIRC5|332 ,  ...

  • 30 genes correlated to 'NUMBER_PACK_YEARS_SMOKED'.

    • C5ORF33|133686 ,  C17ORF42|79736 ,  AZU1|566 ,  DSN1|79980 ,  ABCA3|21 ,  ...

  • 30 genes correlated to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

    • ANKRD33|341405 ,  GPR15|2838 ,  HIST1H2BG|8339 ,  HIST1H2BJ|8970 ,  ZNF695|57116 ,  ...

  • 1 gene correlated to 'COMPLETENESS_OF_RESECTION'.

    • KATNAL2|83473

  • 30 genes correlated to 'RACE'.

    • CRYBB2|1415 ,  NOTCH2NL|388677 ,  ULK4|54986 ,  POLR2J3|548644 ,  POLR2J4|84820 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'PATHOLOGY_M_STAGE', 'KARNOFSKY_PERFORMANCE_SCORE', 'RADIATIONS_RADIATION_REGIMENINDICATION', 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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=11 younger N=19
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=0 lower stage N=30
PATHOLOGY_N_STAGE Spearman correlation test N=30 higher stage N=8 lower stage N=22
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test N=4 male N=4 female N=0
KARNOFSKY_PERFORMANCE_SCORE Spearman correlation test   N=0        
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
RADIATIONS_RADIATION_REGIMENINDICATION Wilcoxon test   N=0        
NUMBER_PACK_YEARS_SMOKED Spearman correlation test N=30 higher number_pack_years_smoked N=20 lower number_pack_years_smoked N=10
YEAR_OF_TOBACCO_SMOKING_ONSET Spearman correlation test N=30 higher year_of_tobacco_smoking_onset N=21 lower year_of_tobacco_smoking_onset N=9
COMPLETENESS_OF_RESECTION Kruskal-Wallis test N=1        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1.  Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0-224 (median=18.1)
  censored N = 356
  death N = 157
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 65.28 (10)
  Significant markers N = 30
  pos. correlated 11
  neg. correlated 19
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

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

SpearmanCorr corrP Q
GPR15|2838 -0.2626 1.496e-08 0.000178
SLC40A1|30061 0.2507 2.335e-08 0.000178
C9ORF140|89958 -0.249 2.916e-08 0.000178
C7ORF68|29923 -0.2463 4.158e-08 0.00019
EDA2R|60401 0.2428 6.77e-08 0.000208
PLA1A|51365 0.2425 6.81e-08 0.000208
AHRR|57491 -0.2409 8.596e-08 0.000214
SRM|6723 -0.2392 1.037e-07 0.000214
FRZB|2487 0.2391 1.052e-07 0.000214
ZNF598|90850 -0.2372 1.328e-07 0.000243
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

Table S4.  Basic characteristics of clinical feature: 'NEOPLASM_DISEASESTAGE'

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 5
  STAGE IA 133
  STAGE IB 140
  STAGE II 1
  STAGE IIA 51
  STAGE IIB 72
  STAGE IIIA 73
  STAGE IIIB 11
  STAGE IV 27
     
  Significant markers N = 30
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'

kruskal_wallis_P Q
RASGRP2|10235 7.197e-09 7.69e-05
FAM117A|81558 8.4e-09 7.69e-05
PTGDS|5730 2.353e-08 0.000144
RBP5|83758 5.925e-08 0.000271
BLK|640 8.318e-08 0.000305
CD40LG|959 1.326e-07 0.000329
STAP1|26228 1.379e-07 0.000329
SEPT1|1731 1.607e-07 0.000329
FAM125B|89853 1.639e-07 0.000329
CCL19|6363 1.966e-07 0.000329
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 1.84 (0.74)
  N
  T1 168
  T2 277
  T3 47
  T4 19
     
  Significant markers N = 30
  pos. correlated 0
  neg. correlated 30
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
RASGRP2|10235 -0.2954 9.441e-12 6.86e-08
C14ORF139|79686 -0.2952 9.852e-12 6.86e-08
PTGDS|5730 -0.2937 1.272e-11 6.86e-08
GP1BA|2811 -0.2957 1.499e-11 6.86e-08
FAM125B|89853 -0.2909 2.005e-11 7.35e-08
C9ORF45|81571 -0.2848 5.423e-11 1.66e-07
TNFRSF13B|23495 -0.2793 1.75e-10 4.58e-07
MAP4K1|11184 -0.2737 3.128e-10 7.16e-07
MS4A1|931 -0.2724 3.944e-10 8.03e-07
ST8SIA1|6489 -0.2707 4.947e-10 8.17e-07
Clinical variable #5: 'PATHOLOGY_N_STAGE'

30 genes related to 'PATHOLOGY_N_STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY_N_STAGE'

PATHOLOGY_N_STAGE Mean (SD) 0.5 (0.75)
  N
  N0 330
  N1 96
  N2 74
  N3 2
     
  Significant markers N = 30
  pos. correlated 8
  neg. correlated 22
List of top 10 genes differentially expressed by 'PATHOLOGY_N_STAGE'

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_N_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
ARID4A|5926 -0.2428 3.593e-08 0.000453
RCOR3|55758 -0.2404 4.946e-08 0.000453
ACSS1|84532 -0.228 2.423e-07 0.00127
FAM117A|81558 -0.2265 2.918e-07 0.00127
RARS|5917 0.22 6.402e-07 0.00127
FLJ42875|440556 -0.2218 6.568e-07 0.00127
MRPS12|6183 0.2193 7.021e-07 0.00127
TBRG4|9238 0.2186 7.571e-07 0.00127
RRM2|6241 0.2177 8.436e-07 0.00127
EPM2AIP1|9852 -0.2174 8.761e-07 0.00127
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
  class0 345
  class1 25
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

4 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 276
  MALE 238
     
  Significant markers N = 4
  Higher in MALE 4
  Higher in FEMALE 0
List of 4 genes differentially expressed by 'GENDER'

Table S12.  Get Full Table List of 4 genes differentially expressed by 'GENDER'. 26 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HDHD1A|8226 15905 1.048e-23 1.37e-20 0.7568
NCRNA00183|554203 16549 2.877e-22 3.29e-19 0.7481
CYORF15A|246126 8493 2.149e-21 2.32e-18 0.9912
CYORF15B|84663 8029 1.665e-20 1.69e-17 0.9922
Clinical variable #8: 'KARNOFSKY_PERFORMANCE_SCORE'

No gene related to 'KARNOFSKY_PERFORMANCE_SCORE'.

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

KARNOFSKY_PERFORMANCE_SCORE Mean (SD) 84.65 (21)
  Significant markers N = 0
Clinical variable #9: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

Table S14.  Basic characteristics of clinical feature: 'HISTOLOGICAL_TYPE'

HISTOLOGICAL_TYPE Labels N
  LUNG ACINAR ADENOCARCINOMA 19
  LUNG ADENOCARCINOMA MIXED SUBTYPE 107
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 318
  LUNG BRONCHIOLOALVEOLAR CARCINOMA MUCINOUS 5
  LUNG BRONCHIOLOALVEOLAR CARCINOMA NONMUCINOUS 19
  LUNG CLEAR CELL ADENOCARCINOMA 2
  LUNG MICROPAPILLARY ADENOCARCINOMA 3
  LUNG MUCINOUS ADENOCARCINOMA 2
  LUNG PAPILLARY ADENOCARCINOMA 23
  LUNG SIGNET RING ADENOCARCINOMA 1
  LUNG SOLID PATTERN PREDOMINANT ADENOCARCINOMA 5
  MUCINOUS (COLLOID) CARCINOMA 10
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
KCNQ1|3784 2.903e-09 5.32e-05
ATAD5|79915 8.247e-08 0.000716
CCNF|899 1.442e-07 0.000716
MECOM|2122 1.774e-07 0.000716
BIRC5|332 3.105e-07 0.000716
GINS2|51659 3.604e-07 0.000716
SLC44A4|80736 3.698e-07 0.000716
CCNE2|9134 3.759e-07 0.000716
KPNA2|3838 3.968e-07 0.000716
H2AFZ|3015 4.22e-07 0.000716
Clinical variable #10: 'RADIATIONS_RADIATION_REGIMENINDICATION'

No gene related to 'RADIATIONS_RADIATION_REGIMENINDICATION'.

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

RADIATIONS_RADIATION_REGIMENINDICATION Labels N
  NO 21
  YES 493
     
  Significant markers N = 0
Clinical variable #11: 'NUMBER_PACK_YEARS_SMOKED'

30 genes related to 'NUMBER_PACK_YEARS_SMOKED'.

Table S17.  Basic characteristics of clinical feature: 'NUMBER_PACK_YEARS_SMOKED'

NUMBER_PACK_YEARS_SMOKED Mean (SD) 41.57 (27)
  Significant markers N = 30
  pos. correlated 20
  neg. correlated 10
List of top 10 genes differentially expressed by 'NUMBER_PACK_YEARS_SMOKED'

Table S18.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER_PACK_YEARS_SMOKED' by Spearman correlation test

SpearmanCorr corrP Q
C5ORF33|133686 0.2511 1.905e-06 0.0349
C17ORF42|79736 0.2326 1.07e-05 0.0544
AZU1|566 -0.2504 1.261e-05 0.0544
DSN1|79980 0.2301 1.341e-05 0.0544
ABCA3|21 -0.2289 1.485e-05 0.0544
SYCE2|256126 0.2265 2.1e-05 0.0641
C3ORF26|84319 0.2204 3.096e-05 0.0642
ETS2|2114 -0.2171 4.11e-05 0.0642
C18ORF19|125228 0.216 4.498e-05 0.0642
MRPS30|10884 0.2146 5.043e-05 0.0642
Clinical variable #12: 'YEAR_OF_TOBACCO_SMOKING_ONSET'

30 genes related to 'YEAR_OF_TOBACCO_SMOKING_ONSET'.

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

YEAR_OF_TOBACCO_SMOKING_ONSET Mean (SD) 1964.95 (12)
  Significant markers N = 30
  pos. correlated 21
  neg. correlated 9
List of top 10 genes differentially expressed by 'YEAR_OF_TOBACCO_SMOKING_ONSET'

Table S20.  Get Full Table List of top 10 genes significantly correlated to 'YEAR_OF_TOBACCO_SMOKING_ONSET' by Spearman correlation test

SpearmanCorr corrP Q
ANKRD33|341405 0.3863 8.502e-08 0.00156
GPR15|2838 0.3086 4.5e-07 0.00412
HIST1H2BG|8339 0.2999 7.602e-07 0.00416
HIST1H2BJ|8970 0.292 9.084e-07 0.00416
ZNF695|57116 0.2769 4.171e-06 0.0128
HIST1H4E|8367 0.306 4.181e-06 0.0128
JMJD6|23210 0.2708 5.666e-06 0.0144
SLC7A5|8140 0.2687 6.726e-06 0.0144
FOLR1|2348 -0.2678 7.49e-06 0.0144
HIST1H3D|8351 0.2733 8.134e-06 0.0144
Clinical variable #13: 'COMPLETENESS_OF_RESECTION'

One gene related to 'COMPLETENESS_OF_RESECTION'.

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

COMPLETENESS_OF_RESECTION Labels N
  R0 342
  R1 12
  R2 4
  RX 25
     
  Significant markers N = 1
List of one gene differentially expressed by 'COMPLETENESS_OF_RESECTION'

Table S22.  Get Full Table List of one gene differentially expressed by 'COMPLETENESS_OF_RESECTION'

kruskal_wallis_P Q
KATNAL2|83473 1.223e-05 0.224
Clinical variable #14: 'RACE'

30 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 8
  BLACK OR AFRICAN AMERICAN 51
  WHITE 387
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S24.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
CRYBB2|1415 1e-10 1.83e-06
NOTCH2NL|388677 4.03e-09 3.69e-05
ULK4|54986 7.193e-09 4.39e-05
POLR2J3|548644 2.389e-08 0.000109
POLR2J4|84820 2.405e-07 0.000881
TUBB8|347688 7.352e-07 0.00224
LOC90784|90784 1.929e-06 0.00505
SPDYE2|441273 3.041e-06 0.00638
C6ORF106|64771 3.134e-06 0.00638
PRSS45|377047 3.662e-06 0.00671
Clinical variable #15: '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 381
     
  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 = 514

  • Number of genes = 18319

  • Number of clinical features = 15

Selected clinical features

  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] 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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