Correlation between mRNAseq expression and clinical features
Rectum Adenocarcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C17H1H74
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/C17H1H74
Overview
Introduction

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

Summary

Testing the association between 18107 genes and 11 clinical features across 163 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.

  • 5 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • OR6W1P|89883 ,  LOC284232|284232 ,  ATP6V1G2|534 ,  AP1S2|8905 ,  NBPF3|84224

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

    • SCG2|7857 ,  ZFHX4|79776 ,  PLN|5350 ,  PRELP|5549 ,  NEXN|91624

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

    • OR6W1P|89883

  • 23 genes correlated to 'GENDER'.

    • XIST|7503 ,  RPS4Y1|6192 ,  ZFY|7544 ,  TSIX|9383 ,  DDX3Y|8653 ,  ...

  • 55 genes correlated to 'HISTOLOGICAL.TYPE'.

    • AGR3|155465 ,  MYT1L|23040 ,  RAB26|25837 ,  SPDEF|25803 ,  PIPOX|51268 ,  ...

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

    • HIST1H2AE|3012 ,  CTBP1|1487 ,  DCDC2B|149069 ,  MSLNL|401827 ,  SLC25A4|291 ,  ...

  • No genes correlated to 'Time to Death', 'AGE', 'PATHOLOGY.N.STAGE', 'COMPLETENESS.OF.RESECTION', 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=0        
NEOPLASM DISEASESTAGE ANOVA test N=5        
PATHOLOGY T STAGE Spearman correlation test N=5 higher stage N=5 lower stage N=0
PATHOLOGY N STAGE Spearman correlation test   N=0        
PATHOLOGY M STAGE ANOVA test N=1        
GENDER t test N=23 male N=13 female N=10
HISTOLOGICAL TYPE t test N=55 rectal mucinous adenocarcinoma N=51 rectal adenocarcinoma N=4
RADIATIONS RADIATION REGIMENINDICATION t test N=9 yes N=7 no N=2
COMPLETENESS OF RESECTION ANOVA test   N=0        
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) 0.2-129.3 (median=14)
  censored N = 130
  death N = 21
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 64.91 (12)
  Significant markers N = 0
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

5 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S3.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 30
  STAGE II 8
  STAGE IIA 38
  STAGE IIB 2
  STAGE IIC 2
  STAGE III 6
  STAGE IIIA 9
  STAGE IIIB 23
  STAGE IIIC 14
  STAGE IV 17
  STAGE IVA 9
     
  Significant markers N = 5
List of 5 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S4.  Get Full Table List of 5 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
OR6W1P|89883 1.233e-09 2.23e-05
LOC284232|284232 1.321e-06 0.0239
ATP6V1G2|534 1.743e-06 0.0316
AP1S2|8905 1.967e-06 0.0356
NBPF3|84224 2.477e-06 0.0448

Figure S1.  Get High-res Image As an example, this figure shows the association of OR6W1P|89883 to 'NEOPLASM.DISEASESTAGE'. P value = 1.23e-09 with ANOVA analysis.

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

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

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.8 (0.67)
  N
  1 9
  2 29
  3 110
  4 14
     
  Significant markers N = 5
  pos. correlated 5
  neg. correlated 0
List of 5 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S6.  Get Full Table List of 5 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
SCG2|7857 0.398 1.715e-07 0.00311
ZFHX4|79776 0.3721 1.368e-06 0.0248
PLN|5350 0.3671 1.664e-06 0.0301
PRELP|5549 0.3646 1.839e-06 0.0333
NEXN|91624 0.3626 2.123e-06 0.0384

Figure S2.  Get High-res Image As an example, this figure shows the association of SCG2|7857 to 'PATHOLOGY.T.STAGE'. P value = 1.71e-07 with Spearman correlation analysis.

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

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

Table S7.  Basic characteristics of clinical feature: 'PATHOLOGY.N.STAGE'

PATHOLOGY.N.STAGE Mean (SD) 0.68 (0.79)
  N
  0 83
  1 45
  2 32
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 124
  M1 21
  M1A 2
  MX 14
     
  Significant markers N = 1
List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

Table S9.  Get Full Table List of one gene differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
OR6W1P|89883 3.137e-12 5.68e-08

Figure S3.  Get High-res Image As an example, this figure shows the association of OR6W1P|89883 to 'PATHOLOGY.M.STAGE'. P value = 3.14e-12 with ANOVA analysis.

Clinical variable #7: 'GENDER'

23 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 73
  MALE 90
     
  Significant markers N = 23
  Higher in MALE 13
  Higher in FEMALE 10
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 -30.65 1.225e-60 2.22e-56 0.9988
RPS4Y1|6192 21.11 3.794e-33 6.87e-29 0.9968
ZFY|7544 21.72 9.53e-33 1.73e-28 0.9944
TSIX|9383 -14.84 1.57e-28 2.84e-24 0.9763
DDX3Y|8653 21.52 3.667e-24 6.64e-20 0.9989
NLGN4Y|22829 16.98 5.722e-23 1.04e-18 0.9869
PRKY|5616 11.22 1.871e-19 3.39e-15 0.9068
KDM5D|8284 17.83 2.859e-19 5.17e-15 0.9976
TMSB4Y|9087 12.93 5.279e-18 9.55e-14 0.931
CYORF15B|84663 14.34 1.957e-16 3.54e-12 0.9794

Figure S4.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 1.22e-60 with T-test analysis.

Clinical variable #8: 'HISTOLOGICAL.TYPE'

55 genes related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  RECTAL ADENOCARCINOMA 144
  RECTAL MUCINOUS ADENOCARCINOMA 13
     
  Significant markers N = 55
  Higher in RECTAL MUCINOUS ADENOCARCINOMA 51
  Higher in RECTAL ADENOCARCINOMA 4
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'

T(pos if higher in 'RECTAL MUCINOUS ADENOCARCINOMA') ttestP Q AUC
AGR3|155465 10.19 4.943e-14 8.93e-10 0.867
MYT1L|23040 10.24 5.593e-13 1.01e-08 0.9545
RAB26|25837 10.64 1.479e-10 2.67e-06 0.9391
SPDEF|25803 9.95 4.574e-10 8.26e-06 0.9327
PIPOX|51268 -9 9.097e-10 1.64e-05 0.8552
SERPINA1|5265 10.56 9.105e-10 1.64e-05 0.945
CA8|767 9.34 1.447e-09 2.61e-05 0.9012
MUC2|4583 8.6 2.388e-09 4.31e-05 0.8873
NEURL|9148 8.67 3.654e-09 6.6e-05 0.8857
TMEM61|199964 9.43 3.878e-09 7e-05 0.9291

Figure S5.  Get High-res Image As an example, this figure shows the association of AGR3|155465 to 'HISTOLOGICAL.TYPE'. P value = 4.94e-14 with T-test analysis.

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

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

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 6
  YES 157
     
  Significant markers N = 9
  Higher in YES 7
  Higher in NO 2
List of 9 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S15.  Get Full Table List of 9 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
HIST1H2AE|3012 -8.92 5.351e-14 9.5e-10 0.7771
CTBP1|1487 9.59 2.905e-12 5.16e-08 0.8471
DCDC2B|149069 8.15 5.093e-11 9.04e-07 0.7596
MSLNL|401827 6.85 2.116e-07 0.00376 0.8077
SLC25A4|291 7.61 4.811e-07 0.00854 0.8047
BEST3|144453 8.63 1.019e-06 0.0181 0.8933
FOXL2|668 6.11 1.236e-06 0.0219 0.7874
PCDH11Y|83259 8.41 2.003e-06 0.0355 0.8542
CENPQ|55166 -7.51 2.555e-06 0.0453 0.9034

Figure S6.  Get High-res Image As an example, this figure shows the association of HIST1H2AE|3012 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 5.35e-14 with T-test analysis.

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

No gene related to 'COMPLETENESS.OF.RESECTION'.

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

COMPLETENESS.OF.RESECTION Labels N
  R0 121
  R1 2
  R2 12
  RX 4
     
  Significant markers N = 0
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

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

Table S17.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.68 (5.5)
  Significant markers N = 0
Methods & Data
Input

  • Expresson data file = READ-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt

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

  • Number of patients = 163

  • Number of genes = 18107

  • 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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