Correlation between mRNAseq expression and clinical features
Lung Squamous Cell Carcinoma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C13T9F8N
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/C13T9F8N
Overview
Introduction

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

Summary

Testing the association between 18529 genes and 12 clinical features across 321 samples, statistically thresholded by Q value < 0.05, 9 clinical features related to at least one genes.

  • 5 genes correlated to 'AGE'.

    • PRSS12|8492 ,  ACVR2A|92 ,  SLC35D2|11046 ,  GLB1L|79411 ,  NR2F2|7026

  • 29 genes correlated to 'GENDER'.

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

  • 30 genes correlated to 'HISTOLOGICAL.TYPE'.

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

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

    • MYT1L|23040 ,  FLJ36000|284124 ,  RNF186|54546 ,  C7ORF34|135927 ,  GAGE12J|729396 ,  ...

  • 1 gene correlated to 'YEAROFTOBACCOSMOKINGONSET'.

    • DUS1L|64118

  • 20 genes correlated to 'DISTANT.METASTASIS'.

    • DEDD|9191 ,  TMCO1|54499 ,  PEX19|5824 ,  SDHC|6391 ,  B4GALT3|8703 ,  ...

  • 5 genes correlated to 'LYMPH.NODE.METASTASIS'.

    • STAC2|342667 ,  PSMD5|5711 ,  HGD|3081 ,  TM4SF20|79853 ,  LMOD3|56203

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

    • RNF113B|140432 ,  NARF|26502

  • 5 genes correlated to 'NEOPLASM.DISEASESTAGE'.

    • TMCO1|54499 ,  DEDD|9191 ,  PEX19|5824 ,  LUZP1|7798 ,  SDHC|6391

  • No genes correlated to 'Time to Death', '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=5 older N=4 younger N=1
GENDER t test N=29 male N=12 female N=17
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
HISTOLOGICAL TYPE ANOVA test N=30        
RADIATIONS RADIATION REGIMENINDICATION t test N=6 yes N=6 no N=0
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test N=1 higher yearoftobaccosmokingonset N=1 lower yearoftobaccosmokingonset N=0
DISTANT METASTASIS ANOVA test N=20        
LYMPH NODE METASTASIS ANOVA test N=5        
COMPLETENESS OF RESECTION ANOVA test N=2        
NEOPLASM DISEASESTAGE ANOVA test N=5        
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=12.2)
  censored N = 186
  death N = 118
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

5 genes related to 'AGE'.

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

AGE Mean (SD) 67.39 (8.7)
  Significant markers N = 5
  pos. correlated 4
  neg. correlated 1
List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3.  Get Full Table List of 5 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
PRSS12|8492 0.3402 6.817e-10 1.26e-05
ACVR2A|92 0.2672 1.623e-06 0.0301
SLC35D2|11046 -0.267 1.644e-06 0.0305
GLB1L|79411 0.2647 2.036e-06 0.0377
NR2F2|7026 0.263 2.386e-06 0.0442

Figure S1.  Get High-res Image As an example, this figure shows the association of PRSS12|8492 to 'AGE'. P value = 6.82e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

29 genes related to 'GENDER'.

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

GENDER Labels N
  FEMALE 79
  MALE 242
     
  Significant markers N = 29
  Higher in MALE 12
  Higher in FEMALE 17
List of top 10 genes differentially expressed by 'GENDER'

Table S5.  Get Full Table List of top 10 genes differentially expressed by 'GENDER'

T(pos if higher in 'MALE') ttestP Q AUC
XIST|7503 -33.94 5.652e-94 1.05e-89 0.9697
ZFY|7544 37.83 1.598e-58 2.96e-54 0.9997
PRKY|5616 26.39 4.376e-57 8.1e-53 0.9907
RPS4Y1|6192 36.47 4.146e-50 7.68e-46 1
TSIX|9383 -15.73 3.951e-35 7.32e-31 0.9452
DDX3Y|8653 29.65 3.511e-32 6.5e-28 1
NLGN4Y|22829 20.99 7.588e-28 1.41e-23 0.9928
KDM5D|8284 29.14 1.3e-25 2.41e-21 1
EIF1AY|9086 25.04 2.73e-19 5.05e-15 1
USP9Y|8287 21.3 4.94e-19 9.15e-15 0.9976

Figure S2.  Get High-res Image As an example, this figure shows the association of XIST|7503 to 'GENDER'. P value = 5.65e-94 with T-test analysis.

Clinical variable #4: 'KARNOFSKY.PERFORMANCE.SCORE'

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

Table S6.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 27.36 (39)
  Significant markers N = 0
Clinical variable #5: 'HISTOLOGICAL.TYPE'

30 genes related to 'HISTOLOGICAL.TYPE'.

Table S7.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  LUNG BASALOID SQUAMOUS CELL CARCINOMA 7
  LUNG PAPILLARY SQUAMOUS CELL CARICNOMA 2
  LUNG SMALL CELL SQUAMOUS CELL CARCINOMA 1
  LUNG SQUAMOUS CELL CARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 311
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S8.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

ANOVA_P Q
SNIP1|79753 3.386e-24 6.27e-20
SF3A3|10946 2.924e-23 5.42e-19
XIAP|331 3.388e-20 6.28e-16
UTP11L|51118 3.428e-19 6.35e-15
GNL2|29889 1.69e-16 3.13e-12
INPP5B|3633 4.737e-16 8.77e-12
C1ORF109|54955 1.059e-15 1.96e-11
MEAF6|64769 7.08e-15 1.31e-10
C1ORF122|127687 6.608e-12 1.22e-07
MTF1|4520 1.09e-10 2.02e-06

Figure S3.  Get High-res Image As an example, this figure shows the association of SNIP1|79753 to 'HISTOLOGICAL.TYPE'. P value = 3.39e-24 with ANOVA analysis.

Clinical variable #6: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S9.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 10
  YES 311
     
  Significant markers N = 6
  Higher in YES 6
  Higher in NO 0
List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S10.  Get Full Table List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
MYT1L|23040 6.9 3.565e-10 6.58e-06 0.8029
FLJ36000|284124 10.79 4.695e-10 8.67e-06 0.876
RNF186|54546 6.82 1.215e-09 2.24e-05 0.8059
C7ORF34|135927 7.49 1.215e-08 0.000224 0.7987
GAGE12J|729396 7.87 4.018e-07 0.00742 0.7635
PCDH11Y|83259 9.1 7.118e-07 0.0131 0.8976

Figure S4.  Get High-res Image As an example, this figure shows the association of MYT1L|23040 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 3.57e-10 with T-test analysis.

Clinical variable #7: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

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

NUMBERPACKYEARSSMOKED Mean (SD) 52.59 (32)
  Significant markers N = 0
Clinical variable #8: 'YEAROFTOBACCOSMOKINGONSET'

One gene related to 'YEAROFTOBACCOSMOKINGONSET'.

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

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1958.87 (11)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

Table S13.  Get Full Table List of one gene significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

SpearmanCorr corrP Q
DUS1L|64118 0.3409 3.621e-07 0.00671

Figure S5.  Get High-res Image As an example, this figure shows the association of DUS1L|64118 to 'YEAROFTOBACCOSMOKINGONSET'. P value = 3.62e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #9: 'DISTANT.METASTASIS'

20 genes related to 'DISTANT.METASTASIS'.

Table S14.  Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS Labels N
  M0 279
  M1 4
  MX 32
     
  Significant markers N = 20
List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

Table S15.  Get Full Table List of top 10 genes differentially expressed by 'DISTANT.METASTASIS'

ANOVA_P Q
DEDD|9191 5.837e-10 1.08e-05
TMCO1|54499 1.983e-09 3.67e-05
PEX19|5824 2.353e-09 4.36e-05
SDHC|6391 1.237e-08 0.000229
B4GALT3|8703 5.228e-08 0.000969
IMPA1|3612 1.183e-07 0.00219
PEX2|5828 1.463e-07 0.00271
TAC3|6866 3.317e-07 0.00614
PPIAL4G|644591 5.045e-07 0.00934
C12ORF41|54934 6.055e-07 0.0112

Figure S6.  Get High-res Image As an example, this figure shows the association of DEDD|9191 to 'DISTANT.METASTASIS'. P value = 5.84e-10 with ANOVA analysis.

Clinical variable #10: 'LYMPH.NODE.METASTASIS'

5 genes related to 'LYMPH.NODE.METASTASIS'.

Table S16.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 200
  N1 89
  N2 25
  N3 5
  NX 2
     
  Significant markers N = 5
List of 5 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S17.  Get Full Table List of 5 genes differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
STAC2|342667 2.093e-07 0.00388
PSMD5|5711 3.057e-07 0.00566
HGD|3081 1.219e-06 0.0226
TM4SF20|79853 1.252e-06 0.0232
LMOD3|56203 1.645e-06 0.0305

Figure S7.  Get High-res Image As an example, this figure shows the association of STAC2|342667 to 'LYMPH.NODE.METASTASIS'. P value = 2.09e-07 with ANOVA analysis.

Clinical variable #11: 'COMPLETENESS.OF.RESECTION'

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

Table S18.  Basic characteristics of clinical feature: 'COMPLETENESS.OF.RESECTION'

COMPLETENESS.OF.RESECTION Labels N
  R0 256
  R1 6
  R2 4
  RX 16
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

Table S19.  Get Full Table List of 2 genes differentially expressed by 'COMPLETENESS.OF.RESECTION'

ANOVA_P Q
RNF113B|140432 2.53e-12 4.69e-08
NARF|26502 2.571e-06 0.0476

Figure S8.  Get High-res Image As an example, this figure shows the association of RNF113B|140432 to 'COMPLETENESS.OF.RESECTION'. P value = 2.53e-12 with ANOVA analysis.

Clinical variable #12: 'NEOPLASM.DISEASESTAGE'

5 genes related to 'NEOPLASM.DISEASESTAGE'.

Table S20.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 1
  STAGE IA 53
  STAGE IB 110
  STAGE II 1
  STAGE IIA 29
  STAGE IIB 58
  STAGE IIIA 42
  STAGE IIIB 19
  STAGE IV 4
     
  Significant markers N = 5
List of 5 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S21.  Get Full Table List of 5 genes differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
TMCO1|54499 1.839e-08 0.000341
DEDD|9191 1.357e-07 0.00251
PEX19|5824 2.742e-07 0.00508
LUZP1|7798 7.156e-07 0.0133
SDHC|6391 8.234e-07 0.0153

Figure S9.  Get High-res Image As an example, this figure shows the association of TMCO1|54499 to 'NEOPLASM.DISEASESTAGE'. P value = 1.84e-08 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 = 321

  • Number of genes = 18529

  • Number of clinical features = 12

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

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

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

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[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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