Correlation between mRNAseq expression and clinical features
Head and Neck Squamous Cell Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C1PR7TQV
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/C1PR7TQV
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 18370 genes and 13 clinical features across 408 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 1 gene correlated to 'Time to Death'.

    • UBTF|7343

  • 5 genes correlated to 'AGE'.

    • RNASE3|6037 ,  ABAT|18 ,  C1ORF103|55791 ,  HN1L|90861 ,  PLCH1|23007

  • 3 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • ZC3HAV1|56829 ,  TNF|7124 ,  TRIM25|7706

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

    • C5ORF20|140947 ,  LRRC8A|56262 ,  WDR37|22884 ,  MSL3|10943 ,  TCEANC|170082 ,  ...

  • 57 genes correlated to 'PATHOLOGY.N.STAGE'.

    • MPZL2|10205 ,  PDXP|57026 ,  APOC1|341 ,  SPRR2F|6705 ,  TGM1|7051 ,  ...

  • 269 genes correlated to 'PATHOLOGY.M.STAGE'.

    • LOC649330|649330 ,  PIK3CG|5294 ,  SUMO1P3|474338 ,  SFRS11|9295 ,  ARHGAP31|57514 ,  ...

  • 158 genes correlated to 'GENDER'.

    • HDHD1A|8226 ,  CYORF15A|246126 ,  CYORF15B|84663 ,  CA5BP|340591 ,  FAM64A|54478 ,  ...

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

    • NFATC2|4773 ,  LIMS1|3987 ,  NHSL2|340527 ,  ZNF827|152485 ,  SPATA13|221178 ,  ...

  • 84 genes correlated to 'NUMBERPACKYEARSSMOKED'.

    • TMTC3|160418 ,  TMSL3|7117 ,  LASS6|253782 ,  DPH3|285381 ,  LRP4|4038 ,  ...

  • 92 genes correlated to 'NUMBER.OF.LYMPH.NODES'.

    • ARL4C|10123 ,  PPEF1|5475 ,  MPZL2|10205 ,  ALS2CL|259173 ,  SLC13A4|26266 ,  ...

  • 9 genes correlated to 'RACE'.

    • LRRC37A2|474170 ,  LRRC37A|9884 ,  SERPINC1|462 ,  LOC441455|441455 ,  GCAT|23464 ,  ...

  • No genes correlated to 'HISTOLOGICAL.TYPE', 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=1 shorter survival N=0 longer survival N=1
AGE Spearman correlation test N=5 older N=2 younger N=3
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=3        
PATHOLOGY T STAGE Spearman correlation test N=41 higher stage N=9 lower stage N=32
PATHOLOGY N STAGE Spearman correlation test N=57 higher stage N=16 lower stage N=41
PATHOLOGY M STAGE Wilcoxon test N=269 mx N=269 m0 N=0
GENDER Wilcoxon test N=158 male N=158 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test   N=0        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=178 yes N=178 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test N=84 higher numberpackyearssmoked N=72 lower numberpackyearssmoked N=12
NUMBER OF LYMPH NODES Spearman correlation test N=92 higher number.of.lymph.nodes N=47 lower number.of.lymph.nodes N=45
RACE Kruskal-Wallis test N=9        
ETHNICITY Wilcoxon 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 (Years) 2-3837 (median=643)
  censored N = 249
  death N = 99
     
  Significant markers N = 1
  associated with shorter survival 0
  associated with longer survival 1
List of one gene differentially expressed by 'Time to Death'

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
UBTF|7343 0.24 1.125e-05 0.21 0.351
Clinical variable #2: 'AGE'

5 genes related to 'AGE'.

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

AGE Mean (SD) 60.78 (12)
  Significant markers N = 5
  pos. correlated 2
  neg. correlated 3
List of 5 genes differentially expressed by 'AGE'

Table S4.  Get Full Table List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
RNASE3|6037 0.3027 6.203e-07 0.0114
ABAT|18 -0.2279 3.397e-06 0.0624
C1ORF103|55791 -0.2278 3.448e-06 0.0633
HN1L|90861 -0.222 6.125e-06 0.112
PLCH1|23007 0.2224 6.592e-06 0.121
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

3 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 24
  STAGE II 61
  STAGE III 68
  STAGE IVA 190
  STAGE IVB 9
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S6.  Get Full Table List of 3 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
ZC3HAV1|56829 1.395e-06 0.0256
TNF|7124 2.644e-06 0.0486
TRIM25|7706 7.139e-06 0.131
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

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

PATHOLOGY.T.STAGE Mean (SD) 2.85 (1)
  N
  1 39
  2 105
  3 84
  4 129
     
  Significant markers N = 41
  pos. correlated 9
  neg. correlated 32
List of top 10 genes differentially expressed by 'PATHOLOGY.T.STAGE'

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

SpearmanCorr corrP Q
C5ORF20|140947 -0.2957 1.564e-08 0.000287
LRRC8A|56262 0.2936 1.577e-08 0.00029
WDR37|22884 -0.2828 5.475e-08 0.00101
MSL3|10943 -0.2814 6.363e-08 0.00117
TCEANC|170082 -0.279 8.32e-08 0.00153
ADM|133 0.275 1.292e-07 0.00237
CX3CR1|1524 -0.2746 1.47e-07 0.0027
FRMD4A|55691 -0.27 2.228e-07 0.00409
DDIT4|54541 0.2689 2.505e-07 0.0046
C14ORF139|79686 -0.2661 3.363e-07 0.00618
Clinical variable #5: 'PATHOLOGY.N.STAGE'

57 genes related to 'PATHOLOGY.N.STAGE'.

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

PATHOLOGY.N.STAGE Mean (SD) 1.03 (0.95)
  N
  0 132
  1 53
  2 129
  3 7
     
  Significant markers N = 57
  pos. correlated 16
  neg. correlated 41
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MPZL2|10205 -0.3078 1.801e-08 0.000331
PDXP|57026 0.2992 4.634e-08 0.000851
APOC1|341 0.2887 1.403e-07 0.00258
SPRR2F|6705 -0.2837 2.924e-07 0.00537
TGM1|7051 -0.2812 3.031e-07 0.00557
FRMD4B|23150 -0.279 3.77e-07 0.00692
MAF1|84232 0.2778 4.251e-07 0.00781
SSH3|54961 -0.277 4.581e-07 0.00841
GPR37|2861 -0.2764 5.092e-07 0.00935
C1ORF216|127703 0.2747 5.786e-07 0.0106
Clinical variable #6: 'PATHOLOGY.M.STAGE'

269 genes related to 'PATHOLOGY.M.STAGE'.

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

PATHOLOGY.M.STAGE Labels N
  M0 104
  MX 43
     
  Significant markers N = 269
  Higher in MX 269
  Higher in M0 0
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

W(pos if higher in 'MX') wilcoxontestP Q AUC
LOC649330|649330 3509 1.509e-09 2.77e-05 0.8229
PIK3CG|5294 946 4.003e-08 0.000735 0.7885
SUMO1P3|474338 3516 5.09e-08 0.000935 0.7862
SFRS11|9295 3514 5.339e-08 0.000981 0.7858
ARHGAP31|57514 961 5.735e-08 0.00105 0.7851
LILRA1|11024 793 7.598e-08 0.0014 0.7946
C15ORF21|283651 3495 8.381e-08 0.00154 0.7815
CPVL|54504 979 8.785e-08 0.00161 0.7811
SRP9|6726 3492 8.994e-08 0.00165 0.7809
PABPN1|8106 3488 9.88e-08 0.00181 0.78
Clinical variable #7: 'GENDER'

158 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 116
  MALE 292
     
  Significant markers N = 158
  Higher in MALE 158
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S14.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 35 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HDHD1A|8226 7291 2.805e-19 5.15e-15 0.7847
CYORF15A|246126 6973 4.822e-16 8.85e-12 0.9984
CYORF15B|84663 5749 2.026e-13 3.72e-09 0.9912
CA5BP|340591 10107 2.081e-10 3.82e-06 0.7016
FAM64A|54478 23646 4.251e-10 7.8e-06 0.6981
CCDC52|152185 23259 3.997e-09 7.33e-05 0.6867
MCM2|4171 23186 6.013e-09 0.00011 0.6845
TFDP2|7029 23008 1.598e-08 0.000293 0.6793
ACBD7|414149 22795 1.915e-08 0.000351 0.6788
ARRDC4|91947 10918 2.138e-08 0.000392 0.6777
Clinical variable #8: 'HISTOLOGICAL.TYPE'

No gene related to 'HISTOLOGICAL.TYPE'.

Table S15.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  HEAD AND NECK SQUAMOUS CELL CARCINOMA 401
  HEAD AND NECK SQUAMOUS CELL CARCINOMA SPINDLE CELL VARIANT 1
  HEAD AND NECK SQUAMOUS CELL CARCINOMA BASALOID TYPE 6
     
  Significant markers N = 0
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 81
  YES 327
     
  Significant markers N = 178
  Higher in YES 178
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S17.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

W(pos if higher in 'YES') wilcoxontestP Q AUC
NFATC2|4773 7006 4.429e-10 8.14e-06 0.7255
LIMS1|3987 7716 5.99e-09 0.00011 0.7087
NHSL2|340527 7645.5 6.198e-09 0.000114 0.7087
ZNF827|152485 7715 6.98e-09 0.000128 0.7078
SPATA13|221178 7819 1.139e-08 0.000209 0.7048
CTDSP2|10106 7840 1.296e-08 0.000238 0.704
SPCS2|9789 18624 1.493e-08 0.000274 0.7031
RAD54L2|23132 7939 2.373e-08 0.000436 0.7003
ELK4|2005 7999 3.406e-08 0.000625 0.698
ZBTB20|26137 7878 4.222e-08 0.000775 0.697
Clinical variable #10: 'NUMBERPACKYEARSSMOKED'

84 genes related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 46.64 (38)
  Significant markers N = 84
  pos. correlated 72
  neg. correlated 12
List of top 10 genes differentially expressed by 'NUMBERPACKYEARSSMOKED'

Table S19.  Get Full Table List of top 10 genes significantly correlated to 'NUMBERPACKYEARSSMOKED' by Spearman correlation test

SpearmanCorr corrP Q
TMTC3|160418 0.3706 6.227e-09 0.000114
TMSL3|7117 -0.3594 1.899e-08 0.000349
LASS6|253782 0.3415 1.024e-07 0.00188
DPH3|285381 -0.3301 2.838e-07 0.00521
LRP4|4038 0.3299 2.877e-07 0.00528
C12ORF66|144577 0.3294 3e-07 0.00551
ZNF462|58499 0.3268 3.764e-07 0.00691
ANAPC1|64682 0.3225 5.45e-07 0.01
ABCC1|4363 0.3215 5.93e-07 0.0109
ZNRF3|84133 0.3215 5.934e-07 0.0109
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

92 genes related to 'NUMBER.OF.LYMPH.NODES'.

Table S20.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 2.33 (4.7)
  Significant markers N = 92
  pos. correlated 47
  neg. correlated 45
List of top 10 genes differentially expressed by 'NUMBER.OF.LYMPH.NODES'

Table S21.  Get Full Table List of top 10 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test

SpearmanCorr corrP Q
ARL4C|10123 0.3233 4.241e-09 7.79e-05
PPEF1|5475 0.3194 7.915e-09 0.000145
MPZL2|10205 -0.299 6.34e-08 0.00116
ALS2CL|259173 -0.2912 1.418e-07 0.0026
SLC13A4|26266 -0.2819 3.956e-07 0.00727
SPOCK1|6695 0.2803 4.283e-07 0.00786
CST2|1470 0.321 5.846e-07 0.0107
GSC|145258 0.276 7.021e-07 0.0129
TGM1|7051 -0.274 7.878e-07 0.0145
BCO2|83875 -0.2727 8.922e-07 0.0164
Clinical variable #12: 'RACE'

9 genes related to 'RACE'.

Table S22.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 1
  ASIAN 10
  BLACK OR AFRICAN AMERICAN 33
  WHITE 352
     
  Significant markers N = 9
List of 9 genes differentially expressed by 'RACE'

Table S23.  Get Full Table List of 9 genes differentially expressed by 'RACE'

ANOVA_P Q
LRRC37A2|474170 2.143e-08 0.000394
LRRC37A|9884 3.639e-07 0.00669
SERPINC1|462 4.211e-07 0.00773
LOC441455|441455 2.744e-06 0.0504
GCAT|23464 3.311e-06 0.0608
SERHL2|253190 8.125e-06 0.149
TBL2|26608 9.486e-06 0.174
NBPF14|25832 1.163e-05 0.214
WBSCR27|155368 1.601e-05 0.294
Clinical variable #13: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S24.  Basic characteristics of clinical feature: 'ETHNICITY'

ETHNICITY Labels N
  HISPANIC OR LATINO 17
  NOT HISPANIC OR LATINO 373
     
  Significant markers N = 0
Methods & Data
Input

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

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

  • Number of patients = 408

  • Number of genes = 18370

  • Number of clinical features = 13

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)
Copyright © 2014 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle