Correlation between mRNAseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
23 September 2013  |  analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1NV9GMV
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1NV9GMV
Overview
Introduction

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

Summary

Testing the association between 23378 genes and 11 clinical features across 273 samples, statistically thresholded by Q value < 0.05, 9 clinical features related to at least one genes.

  • 1 gene correlated to 'Time to Death'.

    • LRRC16B|90668_CALCULATED

  • 16 genes correlated to 'AGE'.

    • TMEM240|339453_CALCULATED ,  PEX7|5191_CALCULATED ,  CXCL1|2919_CALCULATED ,  KIAA0845|?_CALCULATED ,  TMEM132C|92293_CALCULATED ,  ...

  • 180 genes correlated to 'NEOPLASM.DISEASESTAGE'.

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

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

    • SNTB2|6645_CALCULATED ,  PPP1R12A|4659_CALCULATED ,  GNB4|59345_CALCULATED ,  NEXN|91624_CALCULATED ,  YIPF3|25844_CALCULATED ,  ...

  • 1 gene correlated to 'PATHOLOGY.N.STAGE'.

    • ATP2B1|490_CALCULATED

  • 34 genes correlated to 'GENDER'.

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

  • 663 genes correlated to 'HISTOLOGICAL.TYPE'.

    • GEM|2669_CALCULATED ,  FRMD6|122786_CALCULATED ,  ZFPM2|23414_CALCULATED ,  CLMP|79827_CALCULATED ,  RAB31|11031_CALCULATED ,  ...

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

    • CLEC3A|10143_CALCULATED ,  DEC1|50514_CALCULATED ,  LOC100132215|100132215_CALCULATED ,  S100A4|6275_CALCULATED ,  LINC00261|140828_CALCULATED ,  ...

  • 1069 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • MIR3960|100616250_CALCULATED ,  ZNF865|100507290_CALCULATED ,  METAZOA_SRP|?|38OF109_CALCULATED ,  GLTSCR1|29998_CALCULATED ,  METAZOA_SRP|?|35OF109_CALCULATED ,  ...

  • No genes correlated to '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=1 shorter survival N=0 longer survival N=1
AGE Spearman correlation test N=16 older N=11 younger N=5
NEOPLASM DISEASESTAGE ANOVA test N=180        
PATHOLOGY T STAGE Spearman correlation test N=354 higher stage N=314 lower stage N=40
PATHOLOGY N STAGE Spearman correlation test N=1 higher stage N=1 lower stage N=0
PATHOLOGY M STAGE ANOVA test   N=0        
GENDER t test N=34 male N=14 female N=20
HISTOLOGICAL TYPE ANOVA test N=663        
RADIATIONS RADIATION REGIMENINDICATION t test N=6 yes N=5 no N=1
COMPLETENESS OF RESECTION ANOVA test N=1069        
NUMBER OF LYMPH NODES Spearman correlation 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 (Months) 0.1-72.2 (median=2)
  censored N = 214
  death N = 24
     
  Significant markers N = 1
  associated with shorter survival 0
  associated with longer survival 1
List of one gene significantly associated with 'Time to Death' by Cox regression test

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
LRRC16B|90668_CALCULATED 0.47 5.692e-07 0.013 0.23

Figure S1.  Get High-res Image As an example, this figure shows the association of LRRC16B|90668_CALCULATED to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 5.69e-07 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

16 genes related to 'AGE'.

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

AGE Mean (SD) 65.77 (11)
  Significant markers N = 16
  pos. correlated 11
  neg. correlated 5
List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

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

SpearmanCorr corrP Q
TMEM240|339453_CALCULATED -0.3293 3.81e-08 0.000891
PEX7|5191_CALCULATED 0.3238 6.597e-08 0.00154
CXCL1|2919_CALCULATED 0.3095 2.582e-07 0.00604
KIAA0845|?_CALCULATED -0.306 3.579e-07 0.00837
TMEM132C|92293_CALCULATED -0.3153 5.833e-07 0.0136
CRTAP|10491_CALCULATED -0.2993 6.595e-07 0.0154
MASTL|84930_CALCULATED 0.2957 9.075e-07 0.0212
PSMB1|5689_CALCULATED 0.2951 9.588e-07 0.0224
SFT2D1|113402_CALCULATED 0.2947 9.959e-07 0.0233
SNORD52|26797_CALCULATED 0.2946 1.047e-06 0.0245

Figure S2.  Get High-res Image As an example, this figure shows the association of TMEM240|339453_CALCULATED to 'AGE'. P value = 3.81e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

180 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 11
  STAGE IB 26
  STAGE II 24
  STAGE IIA 29
  STAGE IIB 40
  STAGE III 3
  STAGE IIIA 41
  STAGE IIIB 31
  STAGE IIIC 25
  STAGE IV 27
     
  Significant markers N = 180
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
FMO2|2327_CALCULATED 1.409e-14 3.29e-10
MOXD1|26002_CALCULATED 4.333e-13 1.01e-08
RSPO3|84870_CALCULATED 8.288e-13 1.94e-08
GNB4|59345_CALCULATED 5.536e-12 1.29e-07
SERPING1|710_CALCULATED 2.775e-11 6.49e-07
PTGER3|5733_CALCULATED 1.136e-10 2.66e-06
ST6GALNAC5|81849_CALCULATED 2.362e-10 5.52e-06
GREM1|26585_CALCULATED 2.467e-10 5.77e-06
ROR2|4920_CALCULATED 2.615e-10 6.11e-06
GPC6|10082_CALCULATED 3.703e-10 8.65e-06

Figure S3.  Get High-res Image As an example, this figure shows the association of FMO2|2327_CALCULATED to 'NEOPLASM.DISEASESTAGE'. P value = 1.41e-14 with ANOVA analysis.

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

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.93 (0.86)
  N
  1 13
  2 69
  3 106
  4 76
     
  Significant markers N = 354
  pos. correlated 314
  neg. correlated 40
List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

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

SpearmanCorr corrP Q
SNTB2|6645_CALCULATED 0.456 5.807e-15 1.36e-10
PPP1R12A|4659_CALCULATED 0.4182 1.343e-12 3.14e-08
GNB4|59345_CALCULATED 0.4146 2.158e-12 5.04e-08
NEXN|91624_CALCULATED 0.3985 1.765e-11 4.13e-07
YIPF3|25844_CALCULATED -0.3844 1.001e-10 2.34e-06
SGTB|54557_CALCULATED 0.376 2.714e-10 6.34e-06
KCNE4|23704_CALCULATED 0.3743 3.323e-10 7.77e-06
CALD1|800_CALCULATED 0.372 4.344e-10 1.02e-05
MDFIC|29969_CALCULATED 0.3708 5.007e-10 1.17e-05
SFMBT2|57713_CALCULATED 0.367 7.742e-10 1.81e-05

Figure S4.  Get High-res Image As an example, this figure shows the association of SNTB2|6645_CALCULATED to 'PATHOLOGY.T.STAGE'. P value = 5.81e-15 with Spearman correlation analysis.

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

One gene related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE Mean (SD) 1.18 (1.1)
  N
  0 91
  1 78
  2 47
  3 46
     
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

Table S10.  Get Full Table List of one gene significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
ATP2B1|490_CALCULATED 0.294 1.275e-06 0.0298

Figure S5.  Get High-res Image As an example, this figure shows the association of ATP2B1|490_CALCULATED to 'PATHOLOGY.N.STAGE'. P value = 1.28e-06 with Spearman correlation analysis.

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

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

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

PATHOLOGY.M.STAGE Labels N
  M0 243
  M1 18
  MX 12
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

34 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 104
  MALE 169
     
  Significant markers N = 34
  Higher in MALE 14
  Higher in FEMALE 20
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
XIST|7503_CALCULATED -33.06 2.828e-92 6.61e-88 0.9719
TSIX|9383_CALCULATED -31.53 8.578e-89 2.01e-84 0.9723
PRKY|5616_CALCULATED 28.08 1.018e-50 2.38e-46 0.9836
ZFY|7544_CALCULATED 30.94 1.665e-50 3.89e-46 0.985
DDX3Y|8653_CALCULATED 32.24 2.194e-46 5.13e-42 0.9769
KDM5D|8284_CALCULATED 27.7 2.273e-36 5.31e-32 0.9814
EIF1AY|9086_CALCULATED 26.29 1.302e-35 3.04e-31 0.9791
USP9Y|8287_CALCULATED 23.33 6.598e-29 1.54e-24 0.9744
UTY|7404_CALCULATED 21.44 1.853e-26 4.33e-22 0.9733
TXLNG2P|246126_CALCULATED 21.06 1.615e-24 3.77e-20 0.9757

Figure S6.  Get High-res Image As an example, this figure shows the association of XIST|7503_CALCULATED to 'GENDER'. P value = 2.83e-92 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

663 genes related to 'HISTOLOGICAL.TYPE'.

Table S14.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 51
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 130
  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 = 663
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'

ANOVA_P Q
GEM|2669_CALCULATED 5.011e-14 1.17e-09
FRMD6|122786_CALCULATED 5.065e-13 1.18e-08
ZFPM2|23414_CALCULATED 1.692e-12 3.95e-08
CLMP|79827_CALCULATED 3.553e-12 8.31e-08
RAB31|11031_CALCULATED 3.726e-12 8.71e-08
SPG20|23111_CALCULATED 4.843e-12 1.13e-07
MFAP5|8076_CALCULATED 5.078e-12 1.19e-07
TCEAL7|56849_CALCULATED 5.356e-12 1.25e-07
ARHGAP20|57569_CALCULATED 5.953e-12 1.39e-07
DCN|1634_CALCULATED 6.145e-12 1.44e-07

Figure S7.  Get High-res Image As an example, this figure shows the association of GEM|2669_CALCULATED to 'HISTOLOGICAL.TYPE'. P value = 5.01e-14 with ANOVA analysis.

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

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

Table S16.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 7
  YES 266
     
  Significant markers N = 6
  Higher in YES 5
  Higher in NO 1
List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S17.  Get Full Table List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
CLEC3A|10143_CALCULATED 9.8 8.438e-13 1.91e-08 0.7993
DEC1|50514_CALCULATED 7.19 7.089e-11 1.61e-06 0.7701
LOC100132215|100132215_CALCULATED 13.27 1.02e-10 2.31e-06 0.8996
S100A4|6275_CALCULATED 9.02 4.793e-08 0.00109 0.8276
LINC00261|140828_CALCULATED -8.65 2.702e-07 0.00613 0.8106
BC010030|?_CALCULATED 10.8 5.964e-07 0.0135 0.9157

Figure S8.  Get High-res Image As an example, this figure shows the association of CLEC3A|10143_CALCULATED to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 8.44e-13 with T-test analysis.

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

1069 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S18.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 217
  R1 8
  R2 10
  RX 21
     
  Significant markers N = 1069
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S19.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
MIR3960|100616250_CALCULATED 2.023e-28 4.73e-24
ZNF865|100507290_CALCULATED 4.805e-27 1.12e-22
METAZOA_SRP|?|38OF109_CALCULATED 2.74e-26 6.41e-22
GLTSCR1|29998_CALCULATED 5.585e-26 1.31e-21
METAZOA_SRP|?|35OF109_CALCULATED 2.362e-25 5.52e-21
C19ORF68|374920_CALCULATED 9.143e-25 2.14e-20
MIR3648|100500862_CALCULATED 2.174e-24 5.08e-20
RPPH1|85495_CALCULATED 3.161e-24 7.39e-20
ZBTB3|79842_CALCULATED 7.137e-24 1.67e-19
HIATL2|84278_CALCULATED 1.942e-23 4.54e-19

Figure S9.  Get High-res Image As an example, this figure shows the association of MIR3960|100616250_CALCULATED to 'COMPLETENESS.OF.RESECTION'. P value = 2.02e-28 with ANOVA analysis.

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

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

Table S20.  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.clin.merged.picked.txt

  • Number of patients = 273

  • Number of genes = 23378

  • 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)
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