Correlation between mRNAseq expression and clinical features
Head and Neck Squamous Cell Carcinoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C1S46QSV
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/C1S46QSV
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 465 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 11 clinical features related to at least one genes.

  • 3 genes correlated to 'AGE'.

    • RNASE3|6037 ,  C1ORF103|55791 ,  MUTED|63915

  • 3 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • ZC3HAV1|56829 ,  TRIM25|7706 ,  NCOA5|57727

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

    • C5ORF20|140947 ,  CX3CR1|1524 ,  RNPC3|55599 ,  TLR10|81793 ,  SPIB|6689 ,  ...

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

    • MPZL2|10205 ,  APOC1|341 ,  D4S234E|27065 ,  SPRR2F|6705 ,  MASP1|5648 ,  ...

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

    • LOC649330|649330 ,  SFRS11|9295 ,  ERH|2079 ,  ACYP1|97 ,  SRP9|6726 ,  ...

  • 166 genes correlated to 'GENDER'.

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

  • 1 gene correlated to 'HISTOLOGICAL.TYPE'.

    • EHD2|30846

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

    • NFATC2|4773 ,  LIMS1|3987 ,  ZNF827|152485 ,  RAD54L2|23132 ,  NHSL2|340527 ,  ...

  • 23 genes correlated to 'NUMBERPACKYEARSSMOKED'.

    • TMSL3|7117 ,  TMTC3|160418 ,  ALDOC|230 ,  DPH3|285381 ,  DHCR7|1717 ,  ...

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

    • ARL4C|10123 ,  MASP1|5648 ,  PPEF1|5475 ,  NLRX1|79671 ,  BCO2|83875 ,  ...

  • 7 genes correlated to 'RACE'.

    • LRRC37A2|474170 ,  LRRC37A|9884 ,  SERPINC1|462 ,  LOC441455|441455 ,  EP400NL|347918 ,  ...

  • No genes correlated to 'Time to Death', 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=3 older N=1 younger N=2
NEOPLASM DISEASESTAGE Kruskal-Wallis test N=3        
PATHOLOGY T STAGE Spearman correlation test N=87 higher stage N=15 lower stage N=72
PATHOLOGY N STAGE Spearman correlation test N=31 higher stage N=6 lower stage N=25
PATHOLOGY M STAGE Wilcoxon test N=95 mx N=95 m0 N=0
GENDER Wilcoxon test N=166 male N=166 female N=0
HISTOLOGICAL TYPE Kruskal-Wallis test N=1        
RADIATIONS RADIATION REGIMENINDICATION Wilcoxon test N=482 yes N=482 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test N=23 higher numberpackyearssmoked N=17 lower numberpackyearssmoked N=6
NUMBER OF LYMPH NODES Spearman correlation test N=39 higher number.of.lymph.nodes N=13 lower number.of.lymph.nodes N=26
RACE Kruskal-Wallis test N=7        
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 (Years) 2-5480 (median=775)
  censored N = 282
  death N = 113
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

3 genes related to 'AGE'.

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

AGE Mean (SD) 60.7 (12)
  Significant markers N = 3
  pos. correlated 1
  neg. correlated 2
List of 3 genes differentially expressed by 'AGE'

Table S3.  Get Full Table List of 3 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
RNASE3|6037 0.2632 4.103e-06 0.0754
C1ORF103|55791 -0.2106 4.733e-06 0.0869
MUTED|63915 -0.2002 1.397e-05 0.257
Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

3 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 24
  STAGE II 73
  STAGE III 71
  STAGE IVA 223
  STAGE IVB 11
     
  Significant markers N = 3
List of 3 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of 3 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
ZC3HAV1|56829 1.281e-07 0.00235
TRIM25|7706 6.045e-07 0.0111
NCOA5|57727 1.27e-05 0.233
Clinical variable #4: 'PATHOLOGY.T.STAGE'

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

Table S6.  Basic characteristics of clinical feature: 'PATHOLOGY.T.STAGE'

PATHOLOGY.T.STAGE Mean (SD) 2.86 (1)
  N
  0 1
  1 43
  2 121
  3 91
  4 153
     
  Significant markers N = 87
  pos. correlated 15
  neg. correlated 72
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
C5ORF20|140947 -0.315 9.348e-11 1.72e-06
CX3CR1|1524 -0.2875 3.48e-09 6.39e-05
RNPC3|55599 -0.2854 4.174e-09 7.67e-05
TLR10|81793 -0.2868 4.371e-09 8.03e-05
SPIB|6689 -0.2851 5.201e-09 9.55e-05
LRRC8A|56262 0.2811 7.272e-09 0.000134
P2RY13|53829 -0.2808 7.864e-09 0.000144
TCEANC|170082 -0.2798 8.558e-09 0.000157
ADM|133 0.2762 1.353e-08 0.000248
MSL3|10943 -0.2723 2.201e-08 0.000404
Clinical variable #5: 'PATHOLOGY.N.STAGE'

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

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

PATHOLOGY.N.STAGE Mean (SD) 1 (0.95)
  N
  0 161
  1 58
  2 146
  3 7
     
  Significant markers N = 31
  pos. correlated 6
  neg. correlated 25
List of top 10 genes differentially expressed by 'PATHOLOGY.N.STAGE'

Table S9.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
MPZL2|10205 -0.268 1.533e-07 0.00282
APOC1|341 0.2662 1.879e-07 0.00345
D4S234E|27065 -0.2661 1.892e-07 0.00347
SPRR2F|6705 -0.2613 3.973e-07 0.0073
MASP1|5648 -0.2559 5.639e-07 0.0104
MAF1|84232 0.255 6.203e-07 0.0114
TRIM29|23650 -0.2472 1.393e-06 0.0256
WDR37|22884 -0.2471 1.405e-06 0.0258
ARHGAP32|9743 -0.246 1.562e-06 0.0287
SSH3|54961 -0.2443 1.852e-06 0.034
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

Table S10.  Basic characteristics of clinical feature: 'PATHOLOGY.M.STAGE'

PATHOLOGY.M.STAGE Labels N
  M0 153
  MX 50
     
  Significant markers N = 95
  Higher in MX 95
  Higher in M0 0
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S11.  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 5580 1.841e-08 0.000338 0.7699
SFRS11|9295 5837 2.435e-08 0.000447 0.763
ERH|2079 5805 4.04e-08 0.000742 0.7588
ACYP1|97 5789 5.189e-08 0.000953 0.7567
SRP9|6726 5766 7.41e-08 0.00136 0.7537
PABPN1|8106 5706 1.842e-07 0.00338 0.7459
HSPB11|51668 5705 1.87e-07 0.00343 0.7458
METTL3|56339 5699 2.045e-07 0.00376 0.745
HERC2P2|400322 5661 3.585e-07 0.00658 0.74
SPDYA|245711 5569 4.883e-07 0.00897 0.7376
Clinical variable #7: 'GENDER'

166 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 125
  MALE 340
     
  Significant markers N = 166
  Higher in MALE 166
  Higher in FEMALE 0
List of top 10 genes differentially expressed by 'GENDER'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'. 36 significant gene(s) located in sex chromosomes is(are) filtered out.

W(pos if higher in 'MALE') wilcoxontestP Q AUC
HDHD1A|8226 8768 2.587e-22 4.75e-18 0.7937
CYORF15A|246126 8803 2.299e-17 4.22e-13 0.9988
CYORF15B|84663 7024 3.621e-14 6.64e-10 0.9925
CA5BP|340591 12358 4.48e-12 8.22e-08 0.7092
FAM64A|54478 29442 1.815e-10 3.33e-06 0.6928
CCDC52|152185 28981 1.772e-09 3.25e-05 0.6819
ACBD7|414149 28741 2.055e-09 3.77e-05 0.6817
TFDP2|7029 28821 3.795e-09 6.96e-05 0.6781
IQCD|115811 28754 5.197e-09 9.53e-05 0.6766
ZNF232|7775 28488 1.764e-08 0.000323 0.6703
Clinical variable #8: 'HISTOLOGICAL.TYPE'

One gene related to 'HISTOLOGICAL.TYPE'.

Table S14.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  HEAD AND NECK SQUAMOUS CELL CARCINOMA 456
  HEAD AND NECK SQUAMOUS CELL CARCINOMA SPINDLE CELL VARIANT 1
  HEAD AND NECK SQUAMOUS CELL CARCINOMA BASALOID TYPE 8
     
  Significant markers N = 1
List of one gene differentially expressed by 'HISTOLOGICAL.TYPE'

Table S15.  Get Full Table List of one gene differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
EHD2|30846 1.061e-05 0.195
Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 81
  YES 384
     
  Significant markers N = 482
  Higher in YES 482
  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 7470 2.363e-12 4.34e-08 0.7497
LIMS1|3987 8247 3.005e-11 5.52e-07 0.7349
ZNF827|152485 8274 4.096e-11 7.52e-07 0.7333
RAD54L2|23132 8375 6.584e-11 1.21e-06 0.7307
NHSL2|340527 8322.5 8.477e-11 1.56e-06 0.7296
SPATA13|221178 8552 2.195e-10 4.03e-06 0.7243
CTDSP2|10106 8584 2.303e-10 4.23e-06 0.724
ELK4|2005 8655 3.495e-10 6.42e-06 0.7217
H3F3A|3020 22419 4.164e-10 7.65e-06 0.7208
UHMK1|127933 8732 5.47e-10 1e-05 0.7193
Clinical variable #10: 'NUMBERPACKYEARSSMOKED'

23 genes related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 46.06 (36)
  Significant markers N = 23
  pos. correlated 17
  neg. correlated 6
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
TMSL3|7117 -0.3107 2.701e-07 0.00496
TMTC3|160418 0.3092 3.118e-07 0.00573
ALDOC|230 0.3044 4.831e-07 0.00887
DPH3|285381 -0.3007 6.742e-07 0.0124
DHCR7|1717 0.2992 7.675e-07 0.0141
UBE2O|63893 0.2864 2.346e-06 0.0431
PIGS|94005 0.2852 2.59e-06 0.0476
LASS6|253782 0.2843 2.794e-06 0.0513
C12ORF66|144577 0.2838 2.912e-06 0.0535
PDK1|5163 0.2817 3.476e-06 0.0638
Clinical variable #11: 'NUMBER.OF.LYMPH.NODES'

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

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

NUMBER.OF.LYMPH.NODES Mean (SD) 2.22 (4.5)
  Significant markers N = 39
  pos. correlated 13
  neg. correlated 26
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 0.2919 1.33e-08 0.000244
MASP1|5648 -0.28 5.557e-08 0.00102
PPEF1|5475 0.2702 1.785e-07 0.00328
NLRX1|79671 -0.2645 2.942e-07 0.0054
BCO2|83875 -0.258 5.834e-07 0.0107
MPZL2|10205 -0.2553 7.68e-07 0.0141
WDR37|22884 -0.2501 1.308e-06 0.024
MYO1H|283446 -0.2508 1.889e-06 0.0347
NEDD9|4739 0.2435 2.505e-06 0.046
COL22A1|169044 0.2437 2.533e-06 0.0465
Clinical variable #12: 'RACE'

7 genes related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 2
  ASIAN 11
  BLACK OR AFRICAN AMERICAN 34
  WHITE 402
     
  Significant markers N = 7
List of 7 genes differentially expressed by 'RACE'

Table S23.  Get Full Table List of 7 genes differentially expressed by 'RACE'

ANOVA_P Q
LRRC37A2|474170 2.67e-08 0.00049
LRRC37A|9884 1.942e-07 0.00357
SERPINC1|462 1.723e-06 0.0316
LOC441455|441455 3.518e-06 0.0646
EP400NL|347918 5.474e-06 0.101
TBL2|26608 5.791e-06 0.106
GUSBP3|653188 7.704e-06 0.141
Clinical variable #13: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 23
  NOT HISPANIC OR LATINO 410
     
  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 = 465

  • 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)
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