Correlation between mRNAseq expression and clinical features
Liver Hepatocellular Carcinoma (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C11C1VZF
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 17745 genes and 11 clinical features across 357 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 7 clinical features related to at least one genes.

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • CDCA7|83879 ,  EPCAM|4072 ,  RAB3D|9545 ,  PTK7|5754 ,  FAM186B|84070 ,  ...

  • 30 genes correlated to 'NEOPLASM_DISEASESTAGE'.

    • PCCB|5096 ,  BDH1|622 ,  SPP2|6694 ,  RGN|9104 ,  MMP1|4312 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • BDH1|622 ,  PCCB|5096 ,  RGN|9104 ,  CLYBL|171425 ,  SPP2|6694 ,  ...

  • 13 genes correlated to 'GENDER'.

    • HDHD1A|8226 ,  NCRNA00183|554203 ,  CUX2|23316 ,  SDCBP|6386 ,  GGH|8836 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • KCND1|3750 ,  C2ORF63|130162 ,  HOXB3|3213 ,  HOXB5|3215 ,  ABR|29 ,  ...

  • 3 genes correlated to 'COMPLETENESS_OF_RESECTION'.

    • RASEF|158158 ,  DDTL|100037417 ,  AP1S3|130340

  • 30 genes correlated to 'RACE'.

    • XKR9|389668 ,  CYP2D6|1565 ,  PPM1K|152926 ,  TSPAN10|83882 ,  THOC3|84321 ,  ...

  • No genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP', 'PATHOLOGY_N_STAGE', 'PATHOLOGY_M_STAGE', 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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test   N=0        
YEARS_TO_BIRTH Spearman correlation test N=30 older N=12 younger N=18
NEOPLASM_DISEASESTAGE Kruskal-Wallis test N=30        
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=9 lower stage N=21
PATHOLOGY_N_STAGE Wilcoxon test   N=0        
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
GENDER Wilcoxon test N=13 male N=13 female N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
COMPLETENESS_OF_RESECTION Kruskal-Wallis test N=3        
RACE Kruskal-Wallis test N=30        
ETHNICITY Wilcoxon test   N=0        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

No gene related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1.  Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0-120.8 (median=19)
  censored N = 248
  death N = 108
     
  Significant markers N = 0
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 59.61 (13)
  Significant markers N = 30
  pos. correlated 12
  neg. correlated 18
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

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

SpearmanCorr corrP Q
CDCA7|83879 -0.3523 9.422e-12 1.67e-07
EPCAM|4072 -0.3288 3.618e-10 3.21e-06
RAB3D|9545 -0.3148 1.392e-09 8.23e-06
PTK7|5754 -0.3073 3.521e-09 1.56e-05
FAM186B|84070 0.2925 2.252e-08 7.99e-05
OSGIN1|29948 0.2884 3.311e-08 9.23e-05
C9ORF125|84302 -0.2875 3.639e-08 9.23e-05
CELF6|60677 0.2846 5.089e-08 0.000113
PPP1R9A|55607 -0.2843 5.713e-08 0.000113
PET112L|5188 0.282 6.801e-08 0.000121
Clinical variable #3: 'NEOPLASM_DISEASESTAGE'

30 genes related to 'NEOPLASM_DISEASESTAGE'.

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

NEOPLASM_DISEASESTAGE Labels N
  STAGE I 165
  STAGE II 83
  STAGE III 3
  STAGE IIIA 62
  STAGE IIIB 7
  STAGE IIIC 9
  STAGE IV 3
  STAGE IVA 1
  STAGE IVB 2
     
  Significant markers N = 30
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'

kruskal_wallis_P Q
PCCB|5096 1.321e-06 0.0129
BDH1|622 1.453e-06 0.0129
SPP2|6694 2.934e-06 0.0174
RGN|9104 6.866e-06 0.0305
MMP1|4312 1.371e-05 0.0487
LCAT|3931 2.595e-05 0.0712
RAMP3|10268 2.816e-05 0.0712
TMEM110|375346 3.225e-05 0.0712
SRL|6345 3.609e-05 0.0712
F2|2147 4.697e-05 0.0768
Clinical variable #4: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 1.79 (0.91)
  N
  T0 1
  T1 175
  T2 90
  T3 76
  T4 13
     
  Significant markers N = 30
  pos. correlated 9
  neg. correlated 21
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S7.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
BDH1|622 -0.3244 3.833e-10 5.08e-06
PCCB|5096 -0.3213 5.73e-10 5.08e-06
RGN|9104 -0.2988 9.321e-09 4.75e-05
CLYBL|171425 -0.2953 1.425e-08 4.75e-05
SPP2|6694 -0.2969 1.895e-08 4.75e-05
C7ORF68|29923 0.2924 1.996e-08 4.75e-05
DHRS1|115817 -0.2916 2.184e-08 4.75e-05
HPX|3263 -0.291 2.35e-08 4.75e-05
FTCD|10841 -0.2902 2.573e-08 4.75e-05
F2|2147 -0.2898 2.675e-08 4.75e-05
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 Labels N
  N0 247
  N1 4
     
  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
  class0 260
  class1 4
     
  Significant markers N = 0
Clinical variable #7: 'GENDER'

13 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 115
  MALE 242
     
  Significant markers N = 13
  Higher in MALE 13
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 17 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HDHD1A|8226 5237 1.678e-21 2.71e-18 0.8118
NCRNA00183|554203 6894 1.311e-14 1.79e-11 0.7523
CUX2|23316 20039 2.954e-12 2.97e-09 0.7294
SDCBP|6386 20273 3.012e-12 2.97e-09 0.7285
GGH|8836 20209 4.953e-12 4.39e-09 0.7262
ABCB1|5243 20017 2.139e-11 1.81e-08 0.7193
NCK2|8440 8107 1.847e-10 1.42e-07 0.7087
CYORF15A|246126 3578 2.809e-10 2.08e-07 0.9857
ALDH1A1|216 19534 6.998e-10 4.73e-07 0.7019
C20ORF112|140688 8300 7.195e-10 4.73e-07 0.7018
Clinical variable #8: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  FIBROLAMELLAR CARCINOMA 2
  HEPATOCELLULAR CARCINOMA 348
  HEPATOCHOLANGIOCARCINOMA (MIXED) 7
     
  Significant markers N = 30
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'

kruskal_wallis_P Q
KCND1|3750 2.195e-05 0.0496
C2ORF63|130162 2.539e-05 0.0496
HOXB3|3213 2.645e-05 0.0496
HOXB5|3215 3.637e-05 0.0496
ABR|29 3.642e-05 0.0496
PDLIM7|9260 4.959e-05 0.0496
LOC100130776|100130776 5.102e-05 0.0496
AQP11|282679 5.579e-05 0.0496
HOXB6|3216 6.234e-05 0.0496
CACNB3|784 6.69e-05 0.0496
Clinical variable #9: 'COMPLETENESS_OF_RESECTION'

3 genes related to 'COMPLETENESS_OF_RESECTION'.

Table S14.  Basic characteristics of clinical feature: 'COMPLETENESS_OF_RESECTION'

COMPLETENESS_OF_RESECTION Labels N
  R0 314
  R1 15
  R2 1
  RX 20
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

Table S15.  Get Full Table List of 3 genes differentially expressed by 'COMPLETENESS_OF_RESECTION'

kruskal_wallis_P Q
RASEF|158158 2.963e-05 0.296
DDTL|100037417 4.238e-05 0.296
AP1S3|130340 4.998e-05 0.296
Clinical variable #10: 'RACE'

30 genes related to 'RACE'.

Table S16.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 156
  BLACK OR AFRICAN AMERICAN 17
  WHITE 173
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'RACE'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
XKR9|389668 9.166e-22 1.63e-17
CYP2D6|1565 3.118e-16 2.24e-12
PPM1K|152926 3.786e-16 2.24e-12
TSPAN10|83882 1.615e-15 7.17e-12
THOC3|84321 3.838e-14 1.36e-10
POM121L10P|646074 4.824e-14 1.43e-10
FAM128A|653784 6.481e-14 1.64e-10
SIRPB2|284759 1.188e-13 2.63e-10
LOC162632|162632 8.251e-13 1.63e-09
PRSS53|339105 2.15e-11 3.82e-08
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S18.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 12
  NOT HISPANIC OR LATINO 328
     
  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 = 357

  • Number of genes = 17745

  • Number of clinical features = 11

Selected clinical features
  • For clinical features selected for this analysis and their value conozzle.versions, please find a documentation on selected CDEs .

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] 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)