Correlation between mRNAseq expression and clinical features
Lung Squamous Cell Carcinoma (Primary solid tumor)
23 September 2013  |  analyses__2013_09_23
Maintainer Information
Citation Information
doi:10.7908/C1TT4PB2
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1TT4PB2
Overview
Introduction

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

Summary

Testing the association between 18519 genes and 13 clinical features across 386 samples, statistically thresholded by Q value < 0.05, 9 clinical features related to at least one genes.

  • 3 genes correlated to 'AGE'.

    • PRSS12|8492 ,  GLB1L|79411 ,  GLI3|2737

  • 4 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • CA4|762 ,  AGER|177 ,  CENPE|1062 ,  CLDN18|51208

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

    • SFTPC|6440 ,  AGER|177 ,  CNR1|1268 ,  PGC|5225 ,  DMRTC1B|728656 ,  ...

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

    • DEDD|9191 ,  SDHC|6391 ,  PEX19|5824 ,  PPIAL4G|644591 ,  NUDCD1|84955 ,  ...

  • 43 genes correlated to 'GENDER'.

    • XIST|7503 ,  ZFY|7544 ,  PRKY|5616 ,  RPS4Y1|6192 ,  TSIX|9383 ,  ...

  • 23 genes correlated to 'HISTOLOGICAL.TYPE'.

    • SNIP1|79753 ,  SF3A3|10946 ,  UTP11L|51118 ,  XIAP|331 ,  GNL2|29889 ,  ...

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

    • C16ORF81|283860 ,  FLJ36000|284124 ,  RTP1|132112 ,  IL19|29949 ,  GAGE12J|729396

  • 6 genes correlated to 'YEAROFTOBACCOSMOKINGONSET'.

    • DUS1L|64118 ,  LOC729020|729020 ,  C17ORF56|146705 ,  EME1|146956 ,  C16ORF79|283870 ,  ...

  • 2 genes correlated to 'COMPLETENESS.OF.RESECTION'.

    • RNF113B|140432 ,  ATP4B|496

  • No genes correlated to 'Time to Death', 'PATHOLOGY.N.STAGE', 'KARNOFSKY.PERFORMANCE.SCORE', and 'NUMBERPACKYEARSSMOKED'.

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=3 older N=3 younger N=0
NEOPLASM DISEASESTAGE ANOVA test N=4        
PATHOLOGY T STAGE Spearman correlation test N=9 higher stage N=0 lower stage N=9
PATHOLOGY N STAGE Spearman correlation test   N=0        
PATHOLOGY M STAGE ANOVA test N=12        
GENDER t test N=43 male N=14 female N=29
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
HISTOLOGICAL TYPE ANOVA test N=23        
RADIATIONS RADIATION REGIMENINDICATION t test N=5 yes N=5 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test N=6 higher yearoftobaccosmokingonset N=5 lower yearoftobaccosmokingonset N=1
COMPLETENESS OF RESECTION ANOVA test N=2        
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) 0-173.8 (median=11.6)
  censored N = 233
  death N = 119
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

3 genes related to 'AGE'.

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

AGE Mean (SD) 67.11 (8.7)
  Significant markers N = 3
  pos. correlated 3
  neg. correlated 0
List of 3 genes significantly correlated to 'AGE' by Spearman correlation test

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

SpearmanCorr corrP Q
PRSS12|8492 0.2812 2.8e-08 0.000519
GLB1L|79411 0.2502 8.378e-07 0.0155
GLI3|2737 0.2489 9.537e-07 0.0177

Figure S1.  Get High-res Image As an example, this figure shows the association of PRSS12|8492 to 'AGE'. P value = 2.8e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'NEOPLASM.DISEASESTAGE'

4 genes related to 'NEOPLASM.DISEASESTAGE'.

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

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 2
  STAGE IA 68
  STAGE IB 127
  STAGE II 1
  STAGE IIA 46
  STAGE IIB 63
  STAGE IIIA 52
  STAGE IIIB 19
  STAGE IV 5
     
  Significant markers N = 4
List of 4 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S5.  Get Full Table List of 4 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
CA4|762 1.328e-07 0.00246
AGER|177 6.282e-07 0.0116
CENPE|1062 8.377e-07 0.0155
CLDN18|51208 1.211e-06 0.0224

Figure S2.  Get High-res Image As an example, this figure shows the association of CA4|762 to 'NEOPLASM.DISEASESTAGE'. P value = 1.33e-07 with ANOVA analysis.

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

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

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

PATHOLOGY.T.STAGE Mean (SD) 1.95 (0.73)
  N
  1 94
  2 233
  3 42
  4 17
     
  Significant markers N = 9
  pos. correlated 0
  neg. correlated 9
List of 9 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

Table S7.  Get Full Table List of 9 genes significantly correlated to 'PATHOLOGY.T.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
SFTPC|6440 -0.2758 4.285e-08 0.000794
AGER|177 -0.2716 5.937e-08 0.0011
CNR1|1268 -0.261 2.38e-07 0.00441
PGC|5225 -0.2575 7.069e-07 0.0131
DMRTC1B|728656 -0.2611 8.741e-07 0.0162
ADH1B|125 -0.2489 9.281e-07 0.0172
GDF10|2662 -0.2504 1.033e-06 0.0191
CCDC141|285025 -0.2406 2.217e-06 0.041
SMAD6|4091 -0.2368 2.541e-06 0.047

Figure S3.  Get High-res Image As an example, this figure shows the association of SFTPC|6440 to 'PATHOLOGY.T.STAGE'. P value = 4.29e-08 with Spearman correlation analysis.

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 Mean (SD) 0.47 (0.71)
  N
  0 244
  1 100
  2 32
  3 5
     
  Significant markers N = 0
Clinical variable #6: 'PATHOLOGY.M.STAGE'

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

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

PATHOLOGY.M.STAGE Labels N
  M0 328
  M1 5
  MX 47
     
  Significant markers N = 12
List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

Table S10.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGY.M.STAGE'

ANOVA_P Q
DEDD|9191 3.011e-08 0.000558
SDHC|6391 5.725e-08 0.00106
PEX19|5824 2.835e-07 0.00525
PPIAL4G|644591 4.296e-07 0.00795
NUDCD1|84955 4.74e-07 0.00878
POLE3|54107 4.956e-07 0.00917
TMCO1|54499 6.255e-07 0.0116
CKS1B|1163 9.504e-07 0.0176
C1ORF43|25912 9.57e-07 0.0177
POTEF|728378 1.349e-06 0.025

Figure S4.  Get High-res Image As an example, this figure shows the association of DEDD|9191 to 'PATHOLOGY.M.STAGE'. P value = 3.01e-08 with ANOVA analysis.

Clinical variable #7: 'GENDER'

43 genes related to 'GENDER'.

Table S11.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 97
  MALE 289
     
  Significant markers N = 43
  Higher in MALE 14
  Higher in FEMALE 29
List of top 10 genes differentially expressed by 'GENDER'

Table S12.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503 -39.37 9.336e-118 1.73e-113 0.9766
ZFY|7544 43.27 2.167e-79 4.01e-75 0.9993
PRKY|5616 28.03 1.332e-67 2.47e-63 0.9859
RPS4Y1|6192 39.41 2.835e-58 5.25e-54 1
TSIX|9383 -18.63 3.336e-46 6.18e-42 0.9555
DDX3Y|8653 33.64 1.015e-39 1.88e-35 1
KDM5D|8284 37.89 1.091e-39 2.02e-35 1
NLGN4Y|22829 22.84 5.517e-33 1.02e-28 0.9891
USP9Y|8287 27.13 1.273e-27 2.36e-23 0.9979
CYORF15A|246126 25.04 2.257e-22 4.18e-18 0.9977

Figure S5.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 9.34e-118 with T-test analysis.

Clinical variable #8: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S13.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 27.36 (39)
  Significant markers N = 0
Clinical variable #9: 'HISTOLOGICAL.TYPE'

23 genes related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE Labels N
  LUNG BASALOID SQUAMOUS CELL CARCINOMA 11
  LUNG PAPILLARY SQUAMOUS CELL CARICNOMA 5
  LUNG SMALL CELL SQUAMOUS CELL CARCINOMA 1
  LUNG SQUAMOUS CELL CARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 369
     
  Significant markers N = 23
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
SNIP1|79753 8.605e-26 1.59e-21
SF3A3|10946 2.165e-24 4.01e-20
UTP11L|51118 5.699e-20 1.06e-15
XIAP|331 6.217e-20 1.15e-15
GNL2|29889 8.794e-18 1.63e-13
C1ORF109|54955 6.042e-17 1.12e-12
INPP5B|3633 3.836e-16 7.1e-12
MEAF6|64769 7.467e-16 1.38e-11
C1ORF122|127687 5.852e-11 1.08e-06
MTF1|4520 1.232e-10 2.28e-06

Figure S6.  Get High-res Image As an example, this figure shows the association of SNIP1|79753 to 'HISTOLOGICAL.TYPE'. P value = 8.6e-26 with ANOVA analysis.

Clinical variable #10: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

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

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 11
  YES 375
     
  Significant markers N = 5
  Higher in YES 5
  Higher in NO 0
List of 5 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S17.  Get Full Table List of 5 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
C16ORF81|283860 11.2 1.821e-09 3.36e-05 0.8845
FLJ36000|284124 11.58 3.048e-09 5.63e-05 0.8918
RTP1|132112 8.52 7.612e-07 0.0141 0.8637
IL19|29949 9.31 1.157e-06 0.0214 0.8673
GAGE12J|729396 7.56 1.997e-06 0.0369 0.7304

Figure S7.  Get High-res Image As an example, this figure shows the association of C16ORF81|283860 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 1.82e-09 with T-test analysis.

Clinical variable #11: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 52.35 (32)
  Significant markers N = 0
Clinical variable #12: 'YEAROFTOBACCOSMOKINGONSET'

6 genes related to 'YEAROFTOBACCOSMOKINGONSET'.

Table S19.  Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1959.74 (12)
  Significant markers N = 6
  pos. correlated 5
  neg. correlated 1
List of 6 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

Table S20.  Get Full Table List of 6 genes significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

SpearmanCorr corrP Q
DUS1L|64118 0.335 4.463e-08 0.000826
LOC729020|729020 -0.3038 7.992e-07 0.0148
C17ORF56|146705 0.3029 8.655e-07 0.016
EME1|146956 0.2963 1.534e-06 0.0284
C16ORF79|283870 0.2922 2.162e-06 0.04
CCDC154|645811 0.3007 2.205e-06 0.0408

Figure S8.  Get High-res Image As an example, this figure shows the association of DUS1L|64118 to 'YEAROFTOBACCOSMOKINGONSET'. P value = 4.46e-08 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #13: 'COMPLETENESS.OF.RESECTION'

2 genes related to 'COMPLETENESS.OF.RESECTION'.

Table S21.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 312
  R1 7
  R2 4
  RX 18
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S22.  Get Full Table List of 2 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
RNF113B|140432 2.987e-12 5.53e-08
ATP4B|496 1.825e-06 0.0338

Figure S9.  Get High-res Image As an example, this figure shows the association of RNF113B|140432 to 'COMPLETENESS.OF.RESECTION'. P value = 2.99e-12 with ANOVA analysis.

Methods & Data
Input

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

  • Clinical data file = LUSC-TP.clin.merged.picked.txt

  • Number of patients = 386

  • Number of genes = 18519

  • 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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