Correlation between mRNAseq expression and clinical features
Stomach Adenocarcinoma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C15H7DBW
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/C15H7DBW
Overview
Introduction

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

Summary

Testing the association between 23420 genes and 10 clinical features across 152 samples, statistically thresholded by Q value < 0.05, 8 clinical features related to at least one genes.

  • 1 gene correlated to 'AGE'.

    • ADIPOQ|9370_CALCULATED

  • 16 genes correlated to 'GENDER'.

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

  • 57 genes correlated to 'HISTOLOGICAL.TYPE'.

    • MFAP5|8076_CALCULATED ,  MDFIC|29969_CALCULATED ,  FCHSD2|9873_CALCULATED ,  PIP4K2A|5305_CALCULATED ,  RPUSD3|285367_CALCULATED ,  ...

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

    • LOC100132215|100132215_CALCULATED ,  CLEC3A|10143_CALCULATED ,  S100A4|6275_CALCULATED ,  DEC1|50514_CALCULATED ,  LSM12|124801_CALCULATED ,  ...

  • 1 gene correlated to 'DISTANT.METASTASIS'.

    • RPS25|6230_CALCULATED

  • 14 genes correlated to 'LYMPH.NODE.METASTASIS'.

    • LEMD2|221496_CALCULATED ,  SCAF1|58506_CALCULATED ,  SETD1A|9739_CALCULATED ,  ZC3H4|23211_CALCULATED ,  MIR3687|100500815_CALCULATED ,  ...

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

    • ZNF865|100507290_CALCULATED ,  C19ORF68|374920_CALCULATED ,  GLTSCR1|29998_CALCULATED ,  LEMD2|221496_CALCULATED ,  MIR3960|100616250_CALCULATED ,  ...

  • 11 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • SP7|121340_CALCULATED ,  FMO2|2327_CALCULATED ,  P2RY14|9934_CALCULATED ,  MOXD1|26002_CALCULATED ,  HOPX|84525_CALCULATED ,  ...

  • No genes correlated to 'Time to Death', 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=1 older N=0 younger N=1
GENDER t test N=16 male N=10 female N=6
HISTOLOGICAL TYPE ANOVA test N=57        
RADIATIONS RADIATION REGIMENINDICATION t test N=11 yes N=6 no N=5
DISTANT METASTASIS ANOVA test N=1        
LYMPH NODE METASTASIS ANOVA test N=14        
COMPLETENESS OF RESECTION ANOVA test N=901        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
NEOPLASM DISEASESTAGE ANOVA test N=11        
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) 0.1-72.2 (median=1.4)
  censored N = 100
  death N = 15
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

One gene related to 'AGE'.

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

AGE Mean (SD) 67.08 (11)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene significantly correlated to 'AGE' by Spearman correlation test

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

SpearmanCorr corrP Q
ADIPOQ|9370_CALCULATED -0.4803 1.104e-06 0.0259

Figure S1.  Get High-res Image As an example, this figure shows the association of ADIPOQ|9370_CALCULATED to 'AGE'. P value = 1.1e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

16 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 54
  MALE 98
     
  Significant markers N = 16
  Higher in MALE 10
  Higher in FEMALE 6
List of top 10 genes differentially expressed by 'GENDER'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
TSIX|9383_CALCULATED -23.16 1.177e-42 2.76e-38 0.9776
XIST|7503_CALCULATED -23.98 8.645e-42 2.02e-37 0.9771
DDX3Y|8653_CALCULATED 18.27 5.384e-20 1.26e-15 0.9514
ZFY|7544_CALCULATED 17.57 5.816e-20 1.36e-15 0.9638
PRKY|5616_CALCULATED 15.73 7.23e-19 1.69e-14 0.9601
USP9Y|8287_CALCULATED 15.48 6.04e-16 1.41e-11 0.9562
KDM5D|8284_CALCULATED 15.34 3.9e-15 9.13e-11 0.9608
EIF1AY|9086_CALCULATED 13.25 1.125e-12 2.63e-08 0.9508
UTY|7404_CALCULATED 12.02 1.79e-11 4.19e-07 0.9457
NLGN4Y|22829_CALCULATED 10.79 4.495e-10 1.05e-05 0.9227

Figure S2.  Get High-res Image As an example, this figure shows the association of TSIX|9383_CALCULATED to 'GENDER'. P value = 1.18e-42 with T-test analysis.

Clinical variable #4: 'HISTOLOGICAL.TYPE'

57 genes related to 'HISTOLOGICAL.TYPE'.

Table S6.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  STOMACH ADENOCARCINOMA DIFFUSE TYPE 24
  STOMACH ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 74
  STOMACH INTESTINAL ADENOCARCINOMA NOT OTHERWISE SPECIFIED (NOS) 30
  STOMACH INTESTINAL ADENOCARCINOMA TUBULAR TYPE 10
  STOMACH INTESTINAL ADENOCARCINOMA  MUCINOUS TYPE 9
  STOMACH INTESTINAL ADENOCARCINOMA  PAPILLARY TYPE 3
     
  Significant markers N = 57
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S7.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
MFAP5|8076_CALCULATED 3.294e-09 7.71e-05
MDFIC|29969_CALCULATED 9.711e-09 0.000227
FCHSD2|9873_CALCULATED 1.101e-08 0.000258
PIP4K2A|5305_CALCULATED 2.464e-08 0.000577
RPUSD3|285367_CALCULATED 2.786e-08 0.000652
MITF|4286_CALCULATED 6.199e-08 0.00145
ZEB2|9839_CALCULATED 9.957e-08 0.00233
ETS1|2113_CALCULATED 1.101e-07 0.00258
TMEM106A|113277_CALCULATED 1.113e-07 0.00261
ZFPM2|23414_CALCULATED 1.325e-07 0.0031

Figure S3.  Get High-res Image As an example, this figure shows the association of MFAP5|8076_CALCULATED to 'HISTOLOGICAL.TYPE'. P value = 3.29e-09 with ANOVA analysis.

Clinical variable #5: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S8.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 7
  YES 145
     
  Significant markers N = 11
  Higher in YES 6
  Higher in NO 5
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S9.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
LOC100132215|100132215_CALCULATED 10.17 1.849e-11 4.19e-07 0.8611
CLEC3A|10143_CALCULATED 8.26 6.427e-11 1.46e-06 0.8352
S100A4|6275_CALCULATED 8.36 3.364e-09 7.63e-05 0.8709
DEC1|50514_CALCULATED 6.08 3.172e-08 0.000719 0.8352
LSM12|124801_CALCULATED -8.38 4.245e-08 0.000962 0.868
EIF3C|8663|2OF2_CALCULATED -6.57 2.941e-07 0.00667 0.8197
ZFPM1|161882_CALCULATED -7.08 3.593e-07 0.00814 0.7892
LINC00261|140828_CALCULATED -6.62 4.728e-07 0.0107 0.7762
OSTC|58505_CALCULATED 7.12 5.017e-07 0.0114 0.7833
EIF3H|8667_CALCULATED 7.85 1.138e-06 0.0258 0.8502

Figure S4.  Get High-res Image As an example, this figure shows the association of LOC100132215|100132215_CALCULATED to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.85e-11 with T-test analysis.

Clinical variable #6: 'DISTANT.METASTASIS'

One gene related to 'DISTANT.METASTASIS'.

Table S10.  Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS Labels N
  M0 125
  M1 15
  MX 12
     
  Significant markers N = 1
List of one gene differentially expressed by 'DISTANT.METASTASIS'

Table S11.  Get Full Table List of one gene differentially expressed by 'DISTANT.METASTASIS'

ANOVA_P Q
RPS25|6230_CALCULATED 5.894e-07 0.0138

Figure S5.  Get High-res Image As an example, this figure shows the association of RPS25|6230_CALCULATED to 'DISTANT.METASTASIS'. P value = 5.89e-07 with ANOVA analysis.

Clinical variable #7: 'LYMPH.NODE.METASTASIS'

14 genes related to 'LYMPH.NODE.METASTASIS'.

Table S12.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 48
  N1 53
  N2 22
  N3 13
  N3A 5
  NX 11
     
  Significant markers N = 14
List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
LEMD2|221496_CALCULATED 4.77e-08 0.00112
SCAF1|58506_CALCULATED 1.632e-07 0.00382
SETD1A|9739_CALCULATED 1.862e-07 0.00436
ZC3H4|23211_CALCULATED 2.59e-07 0.00606
MIR3687|100500815_CALCULATED 7.578e-07 0.0177
RING1|6015_CALCULATED 9.343e-07 0.0219
CHMP6|79643_CALCULATED 9.691e-07 0.0227
DHX37|57647_CALCULATED 1.392e-06 0.0326
E2F4|1874_CALCULATED 1.819e-06 0.0426
MIR3648|100500862_CALCULATED 1.848e-06 0.0433

Figure S6.  Get High-res Image As an example, this figure shows the association of LEMD2|221496_CALCULATED to 'LYMPH.NODE.METASTASIS'. P value = 4.77e-08 with ANOVA analysis.

Clinical variable #8: 'COMPLETENESS.OF.RESECTION'

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

Table S14.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 102
  R1 7
  R2 10
  RX 22
     
  Significant markers N = 901
List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
ZNF865|100507290_CALCULATED 1.78e-17 4.17e-13
C19ORF68|374920_CALCULATED 9.779e-17 2.29e-12
GLTSCR1|29998_CALCULATED 2.75e-16 6.44e-12
LEMD2|221496_CALCULATED 9.682e-16 2.27e-11
MIR3960|100616250_CALCULATED 1.798e-15 4.21e-11
MIR1281|100302237_CALCULATED 3.042e-15 7.12e-11
ZC3H4|23211_CALCULATED 4.084e-15 9.56e-11
ZBTB3|79842_CALCULATED 4.737e-15 1.11e-10
SRP72|6731_CALCULATED 1.006e-14 2.35e-10
RFX1|5989_CALCULATED 1.642e-14 3.84e-10

Figure S7.  Get High-res Image As an example, this figure shows the association of ZNF865|100507290_CALCULATED to 'COMPLETENESS.OF.RESECTION'. P value = 1.78e-17 with ANOVA analysis.

Clinical variable #9: 'NUMBER.OF.LYMPH.NODES'

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

Table S16.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 4.92 (7)
  Significant markers N = 0
Clinical variable #10: 'NEOPLASM.DISEASESTAGE'

11 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S17.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 5
  STAGE IB 17
  STAGE II 25
  STAGE IIA 5
  STAGE IIB 11
  STAGE III 4
  STAGE IIIA 31
  STAGE IIIB 5
  STAGE IIIC 6
  STAGE IV 26
     
  Significant markers N = 11
List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
SP7|121340_CALCULATED 6.688e-11 1.57e-06
FMO2|2327_CALCULATED 1.02e-10 2.39e-06
P2RY14|9934_CALCULATED 5.704e-08 0.00134
MOXD1|26002_CALCULATED 8.544e-08 0.002
HOPX|84525_CALCULATED 1.898e-07 0.00445
PCOLCE2|26577_CALCULATED 2.422e-07 0.00567
RSPO3|84870_CALCULATED 3.094e-07 0.00725
ITPRIPL2|162073_CALCULATED 3.341e-07 0.00782
LBH|81606_CALCULATED 9.06e-07 0.0212
KCNS3|3790_CALCULATED 9.461e-07 0.0221

Figure S8.  Get High-res Image As an example, this figure shows the association of SP7|121340_CALCULATED to 'NEOPLASM.DISEASESTAGE'. P value = 6.69e-11 with ANOVA analysis.

Methods & Data
Input

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

  • Clinical data file = STAD-TP.clin.merged.picked.txt

  • Number of patients = 152

  • Number of genes = 23420

  • Number of clinical features = 10

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

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

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

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[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 © 2013 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle