Correlation between mRNAseq expression and clinical features
Liver Hepatocellular Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1PR7TR9
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/C1PR7TR9
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 17827 genes and 11 clinical features across 162 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 4 clinical features related to at least one genes.

  • 10 genes correlated to 'AGE'.

    • PCM1|5108 ,  FUT4|2526 ,  RAB3D|9545 ,  PMS2L2|5380 ,  PTK7|5754 ,  ...

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

    • TFAP2A|7020 ,  ALDH4A1|8659 ,  PAH|5053 ,  CARKD|55739 ,  FTCD|10841 ,  ...

  • 112 genes correlated to 'GENDER'.

    • HDHD1A|8226 ,  NCRNA00183|554203 ,  PTGR1|22949 ,  MGST1|4257 ,  GGH|8836 ,  ...

  • 17 genes correlated to 'RACE'.

    • SPG7|6687 ,  TSPAN10|83882 ,  THOC3|84321 ,  POM121L10P|646074 ,  XKR9|389668 ,  ...

  • No genes correlated to 'Time to Death', 'NEOPLASM.DISEASESTAGE', 'PATHOLOGY.N.STAGE', 'PATHOLOGY.M.STAGE', 'HISTOLOGICAL.TYPE', 'COMPLETENESS.OF.RESECTION', 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
Time to Death Cox regression test   N=0        
AGE Spearman correlation test N=10 older N=3 younger N=7
NEOPLASM DISEASESTAGE Kruskal-Wallis test   N=0        
PATHOLOGY T STAGE Spearman correlation test N=15 higher stage N=4 lower stage N=11
PATHOLOGY N STAGE Wilcoxon test   N=0        
PATHOLOGY M STAGE Kruskal-Wallis test   N=0        
GENDER Wilcoxon test N=112 male N=112 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test   N=0        
COMPLETENESS OF RESECTION Kruskal-Wallis test   N=0        
RACE Kruskal-Wallis test N=17        
ETHNICITY Wilcoxon 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) 0-113 (median=13.8)
  censored N = 93
  death N = 66
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

10 genes related to 'AGE'.

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

AGE Mean (SD) 61.59 (14)
  Significant markers N = 10
  pos. correlated 3
  neg. correlated 7
List of 10 genes differentially expressed by 'AGE'

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

SpearmanCorr corrP Q
PCM1|5108 -0.4151 4.803e-08 0.000856
FUT4|2526 -0.4003 1.565e-07 0.00279
RAB3D|9545 -0.361 2.738e-06 0.0488
PMS2L2|5380 0.3555 3.96e-06 0.0706
PTK7|5754 -0.3424 9.372e-06 0.167
PNMAL1|55228 -0.3632 9.573e-06 0.171
CENPBD1|92806 0.3374 1.283e-05 0.229
COL5A3|50509 0.3373 1.294e-05 0.231
PEG3|5178 -0.3345 1.634e-05 0.291
GTF2E2|2961 -0.3331 1.68e-05 0.299
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

No gene related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 64
  STAGE II 37
  STAGE III 2
  STAGE IIIA 34
  STAGE IIIB 4
  STAGE IIIC 6
  STAGE IV 1
  STAGE IVA 1
  STAGE IVB 2
     
  Significant markers N = 0
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 1.97 (0.96)
  N
  1 67
  2 41
  3 44
  4 9
     
  Significant markers N = 15
  pos. correlated 4
  neg. correlated 11
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

Table S6.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
TFAP2A|7020 0.3958 3.753e-07 0.00669
ALDH4A1|8659 -0.3871 3.92e-07 0.00699
PAH|5053 -0.3758 8.989e-07 0.016
CARKD|55739 -0.3661 1.792e-06 0.0319
FTCD|10841 -0.3598 2.771e-06 0.0494
ECHDC1|55862 -0.3549 3.861e-06 0.0688
CLYBL|171425 -0.3542 4.04e-06 0.072
ULBP1|80329 0.3706 4.475e-06 0.0797
C1QL4|338761 0.3881 7.101e-06 0.127
MUC1|4582 0.3427 8.584e-06 0.153
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 Labels N
  class0 103
  class1 3
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 122
  M1 3
  MX 37
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

112 genes related to 'GENDER'.

Table S9.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 62
  MALE 100
     
  Significant markers N = 112
  Higher in MALE 112
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S10.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 21 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HDHD1A|8226 1177 3.479e-11 6.2e-07 0.8102
NCRNA00183|554203 1334 1.174e-09 2.09e-05 0.7848
PTGR1|22949 4822 2.991e-09 5.33e-05 0.7777
MGST1|4257 4785 6.452e-09 0.000115 0.7718
GGH|8836 4775 7.921e-09 0.000141 0.7702
CNN3|1266 4764 9.912e-09 0.000176 0.7684
NCK2|8440 1449 1.29e-08 0.00023 0.7663
BMP8B|656 1391 2.426e-08 0.000432 0.7638
TERF1|7013 4701 3.485e-08 0.00062 0.7582
SPCS1|28972 4682 5.046e-08 0.000898 0.7552
Clinical variable #8: 'HISTOLOGICAL.TYPE'

No gene related to 'HISTOLOGICAL.TYPE'.

Table S11.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  FIBROLAMELLAR CARCINOMA 2
  HEPATOCELLULAR CARCINOMA 158
  HEPATOCHOLANGIOCARCINOMA (MIXED) 2
     
  Significant markers N = 0
Clinical variable #9: 'COMPLETENESS.OF.RESECTION'

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

Table S12.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 133
  R1 11
  R2 1
  RX 12
     
  Significant markers N = 0
Clinical variable #10: 'RACE'

17 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 38
  BLACK OR AFRICAN AMERICAN 8
  WHITE 109
     
  Significant markers N = 17
List of top 10 genes differentially expressed by 'RACE'

Table S14.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

ANOVA_P Q
SPG7|6687 1.437e-07 0.00256
TSPAN10|83882 1.836e-07 0.00327
THOC3|84321 3.033e-07 0.00541
POM121L10P|646074 3.318e-07 0.00591
XKR9|389668 3.68e-07 0.00656
LDHD|197257 4.332e-07 0.00772
CDCA7|83879 1.722e-06 0.0307
HCG4P6|80868 1.968e-06 0.0351
NOL11|25926 6.79e-06 0.121
SCAMP5|192683 7.115e-06 0.127
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S15.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 4
  NOT HISPANIC OR LATINO 144
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 162

  • Number of genes = 17827

  • 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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