Correlation between mRNAseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1MG7N00
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/C1MG7N00
Overview
Introduction

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

Summary

Testing the association between 23365 genes and 11 clinical features across 274 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.

  • 5 genes correlated to 'AGE'.

    • CXCL1|2919_CALCULATED ,  SNORD52|26797_CALCULATED ,  TMEM240|339453_CALCULATED ,  PEX7|5191_CALCULATED ,  TMEM132C|92293_CALCULATED

  • 131 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • FMO2|2327_CALCULATED ,  MOXD1|26002_CALCULATED ,  RSPO3|84870_CALCULATED ,  SERPING1|710_CALCULATED ,  GNB4|59345_CALCULATED ,  ...

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

    • GNB4|59345_CALCULATED ,  NEXN|91624_CALCULATED ,  SNTB2|6645_CALCULATED ,  PPP1R12A|4659_CALCULATED ,  KCNE4|23704_CALCULATED ,  ...

  • 29 genes correlated to 'GENDER'.

    • XIST|7503_CALCULATED ,  TSIX|9383_CALCULATED ,  PRKY|5616_CALCULATED ,  DDX3Y|8653_CALCULATED ,  ZFY|7544_CALCULATED ,  ...

  • 480 genes correlated to 'HISTOLOGICAL.TYPE'.

    • GEM|2669_CALCULATED ,  MFAP5|8076_CALCULATED ,  TCEAL7|56849_CALCULATED ,  GYPC|2995_CALCULATED ,  CLMP|79827_CALCULATED ,  ...

  • 53 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • RNU4ATAC|100151683|2OF8_CALCULATED ,  JA202363|?_CALCULATED ,  SNORD61|26787_CALCULATED ,  5S_RRNA|?|31OF139_CALCULATED ,  HSA-MIR-3074-5P|?_CALCULATED ,  ...

  • 559 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • METAZOA_SRP|?|38OF109_CALCULATED ,  MIR3648|100500862_CALCULATED ,  MIR3960|100616250_CALCULATED ,  METAZOA_SRP|?|35OF109_CALCULATED ,  RPPH1|85495_CALCULATED ,  ...

  • No genes correlated to 'Time to Death', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', and 'NUMBER.OF.LYMPH.NODES'.

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=5 older N=3 younger N=2
NEOPLASM DISEASESTAGE ANOVA test N=131        
PATHOLOGY T STAGE Spearman correlation test N=484 higher stage N=481 lower stage N=3
PATHOLOGY N STAGE Spearman correlation test   N=0        
PATHOLOGY M STAGE ANOVA test   N=0        
GENDER t test N=29 male N=12 female N=17
HISTOLOGICAL TYPE ANOVA test N=480        
RADIATIONS RADIATION REGIMENINDICATION t test N=53 yes N=49 no N=4
COMPLETENESS OF RESECTION ANOVA test N=559        
NUMBER OF LYMPH NODES Spearman correlation 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 (Months) 0.1-105.1 (median=9.2)
  censored N = 193
  death N = 50
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

5 genes related to 'AGE'.

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

AGE Mean (SD) 65.75 (11)
  Significant markers N = 5
  pos. correlated 3
  neg. correlated 2
List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
CXCL1|2919_CALCULATED 0.3134 1.696e-07 0.00396
SNORD52|26797_CALCULATED 0.3011 6.17e-07 0.0144
TMEM240|339453_CALCULATED -0.2971 7.632e-07 0.0178
PEX7|5191_CALCULATED 0.2936 1.047e-06 0.0244
TMEM132C|92293_CALCULATED -0.3036 1.492e-06 0.0349

Figure S1.  Get High-res Image As an example, this figure shows the association of CXCL1|2919_CALCULATED to 'AGE'. P value = 1.7e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

131 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 11
  STAGE IB 25
  STAGE II 24
  STAGE IIA 29
  STAGE IIB 42
  STAGE III 3
  STAGE IIIA 40
  STAGE IIIB 31
  STAGE IIIC 25
  STAGE IV 27
     
  Significant markers N = 131
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
FMO2|2327_CALCULATED 7.393e-15 1.73e-10
MOXD1|26002_CALCULATED 1.263e-12 2.95e-08
RSPO3|84870_CALCULATED 2.918e-12 6.82e-08
SERPING1|710_CALCULATED 9.031e-11 2.11e-06
GNB4|59345_CALCULATED 3.02e-10 7.06e-06
PTGER3|5733_CALCULATED 3.848e-10 8.99e-06
GREM1|26585_CALCULATED 9.028e-10 2.11e-05
ROR2|4920_CALCULATED 1.212e-09 2.83e-05
ST6GALNAC5|81849_CALCULATED 1.483e-09 3.46e-05
P2RY14|9934_CALCULATED 1.801e-09 4.21e-05

Figure S2.  Get High-res Image As an example, this figure shows the association of FMO2|2327_CALCULATED to 'NEOPLASM.DISEASESTAGE'. P value = 7.39e-15 with ANOVA analysis.

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

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.93 (0.86)
  N
  1 13
  2 69
  3 107
  4 76
     
  Significant markers N = 484
  pos. correlated 481
  neg. correlated 3
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
GNB4|59345_CALCULATED 0.4187 1.13e-12 2.64e-08
NEXN|91624_CALCULATED 0.4068 5.543e-12 1.3e-07
SNTB2|6645_CALCULATED 0.4 1.329e-11 3.1e-07
PPP1R12A|4659_CALCULATED 0.3889 5.366e-11 1.25e-06
KCNE4|23704_CALCULATED 0.388 5.963e-11 1.39e-06
PLN|5350_CALCULATED 0.3836 1.021e-10 2.39e-06
SFMBT2|57713_CALCULATED 0.3822 1.204e-10 2.81e-06
AF268386|?_CALCULATED 0.3794 1.69e-10 3.95e-06
RYR2|6262_CALCULATED 0.3756 2.649e-10 6.19e-06
HAND2|9464_CALCULATED 0.3775 2.893e-10 6.76e-06

Figure S3.  Get High-res Image As an example, this figure shows the association of GNB4|59345_CALCULATED to 'PATHOLOGY.T.STAGE'. P value = 1.13e-12 with Spearman correlation analysis.

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

No gene related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE Mean (SD) 1.19 (1.1)
  N
  0 90
  1 78
  2 47
  3 47
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

No gene related to 'PATHOLOGY.M.STAGE'.

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

PATHOLOGY.M.STAGE Labels N
  M0 243
  M1 18
  MX 13
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

29 genes related to 'GENDER'.

Table S10.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 105
  MALE 169
     
  Significant markers N = 29
  Higher in MALE 12
  Higher in FEMALE 17
List of top 10 genes differentially expressed by 'GENDER'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503_CALCULATED -33.32 3.22e-93 7.52e-89 0.9706
TSIX|9383_CALCULATED -31.68 2.155e-89 5.04e-85 0.9713
PRKY|5616_CALCULATED 27.86 1.042e-51 2.44e-47 0.984
DDX3Y|8653_CALCULATED 31.96 1.044e-47 2.44e-43 0.9781
ZFY|7544_CALCULATED 28.51 2.839e-41 6.63e-37 0.9797
KDM5D|8284_CALCULATED 28.44 2.318e-38 5.41e-34 0.9817
EIF1AY|9086_CALCULATED 26.44 7.196e-37 1.68e-32 0.9798
USP9Y|8287_CALCULATED 23.8 1.977e-30 4.62e-26 0.9739
UTY|7404_CALCULATED 21.48 1.872e-26 4.37e-22 0.972
TXLNG2P|246126_CALCULATED 20.77 1.538e-24 3.59e-20 0.9735

Figure S4.  Get High-res Image As an example, this figure shows the association of XIST|7503_CALCULATED to 'GENDER'. P value = 3.22e-93 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

480 genes related to 'HISTOLOGICAL.TYPE'.

Table S12.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 51
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 131
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 35
  STOMACH INTESTINAL ADENOCARCINOMA TUBULAR TYPE 36
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 13
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 5
  STOMACH ADENOCARCINOMA SIGNET RING TYPE 1
     
  Significant markers N = 480
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

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

ANOVA_P Q
GEM|2669_CALCULATED 5.504e-12 1.29e-07
MFAP5|8076_CALCULATED 5.917e-12 1.38e-07
TCEAL7|56849_CALCULATED 1.618e-11 3.78e-07
GYPC|2995_CALCULATED 1.777e-11 4.15e-07
CLMP|79827_CALCULATED 2.901e-11 6.78e-07
ZFPM2|23414_CALCULATED 2.91e-11 6.8e-07
ARHGAP20|57569_CALCULATED 3.933e-11 9.19e-07
DCN|1634_CALCULATED 4.118e-11 9.62e-07
FRMD6|122786_CALCULATED 6.558e-11 1.53e-06
COLEC12|81035_CALCULATED 1.234e-10 2.88e-06

Figure S5.  Get High-res Image As an example, this figure shows the association of GEM|2669_CALCULATED to 'HISTOLOGICAL.TYPE'. P value = 5.5e-12 with ANOVA analysis.

Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

53 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S14.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 7
  YES 267
     
  Significant markers N = 53
  Higher in YES 49
  Higher in NO 4
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
RNU4ATAC|100151683|2OF8_CALCULATED 18.43 2.784e-42 6.25e-38 0.9029
JA202363|?_CALCULATED 15.25 7.47e-33 1.68e-28 0.8742
SNORD61|26787_CALCULATED 13.71 4.762e-29 1.07e-24 0.8163
5S_RRNA|?|31OF139_CALCULATED 13.23 4.938e-26 1.11e-21 0.8321
HSA-MIR-3074-5P|?_CALCULATED 12.27 7.55e-26 1.7e-21 0.7632
AP1B1P1|23782_CALCULATED 13.05 5.102e-24 1.15e-19 0.9
MIR4326|100422945_CALCULATED 11.72 8.993e-23 2.02e-18 0.7755
DQ586086|?_CALCULATED 11.7 1.6e-22 3.59e-18 0.7923
LOC100507140|100507140_CALCULATED 11.64 2.245e-22 5.04e-18 0.8169
MIR219-1|407002_CALCULATED 11.3 3.363e-22 7.55e-18 0.7515

Figure S6.  Get High-res Image As an example, this figure shows the association of RNU4ATAC|100151683|2OF8_CALCULATED to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.78e-42 with T-test analysis.

Clinical variable #10: 'COMPLETENESS.OF.RESECTION'

559 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S16.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 217
  R1 8
  R2 10
  RX 22
     
  Significant markers N = 559
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
METAZOA_SRP|?|38OF109_CALCULATED 6.157e-26 1.44e-21
MIR3648|100500862_CALCULATED 8.303e-25 1.94e-20
MIR3960|100616250_CALCULATED 1.881e-24 4.4e-20
METAZOA_SRP|?|35OF109_CALCULATED 2.734e-24 6.39e-20
RPPH1|85495_CALCULATED 3.607e-24 8.43e-20
MIR3687|100500815_CALCULATED 1.731e-20 4.04e-16
LOC407835|407835_CALCULATED 2.683e-20 6.27e-16
SCARNA2|677766_CALCULATED 6.407e-20 1.5e-15
C19ORF68|374920_CALCULATED 4.928e-19 1.15e-14
SCARNA17|677769_CALCULATED 7.93e-19 1.85e-14

Figure S7.  Get High-res Image As an example, this figure shows the association of METAZOA_SRP|?|38OF109_CALCULATED to 'COMPLETENESS.OF.RESECTION'. P value = 6.16e-26 with ANOVA analysis.

Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

No gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S18.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 4.84 (7.1)
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = STAD-TP.mRNAseq_RPKM_log2.txt

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

  • Number of patients = 274

  • Number of genes = 23365

  • Number of clinical features = 11

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)
Copyright © 2014 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle