Correlation between mRNA expression and clinical features
Overview
Introduction

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

Summary

Testing the association between 17814 genes and 15 clinical features across 1596 samples, statistically thresholded by Q value < 0.05, 14 clinical features related to at least one genes.

  • 3019 genes correlated to 'Time to Death'.

    • KLHL14 ,  ASS1 ,  IGSF11 ,  UPK1B ,  C4ORF32 ,  ...

  • 3653 genes correlated to 'AGE'.

    • GREB1 ,  COL18A1 ,  DUOX2 ,  LDOC1 ,  GALNTL1 ,  ...

  • 17317 genes correlated to 'PRIMARY.SITE.OF.DISEASE'.

    • KLHL14 ,  ZG16 ,  SLC22A2 ,  PDZD3 ,  EMX2 ,  ...

  • 9010 genes correlated to 'GENDER'.

    • ESR1 ,  RSPO1 ,  DDX3Y ,  RPS4Y1 ,  EIF1AY ,  ...

  • 206 genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

    • PPP1R9A ,  VASN ,  MARCH7 ,  CCDC135 ,  POGZ ,  ...

  • 16612 genes correlated to 'HISTOLOGICAL.TYPE'.

    • KLHL14 ,  EMX2 ,  NPR1 ,  FUT4 ,  FXYD2 ,  ...

  • 5976 genes correlated to 'PATHOLOGY.T'.

    • C13ORF3 ,  NR3C1 ,  CDCA7 ,  LIFR ,  C20ORF151 ,  ...

  • 15 genes correlated to 'PATHOLOGY.N'.

    • TNFRSF10C ,  FAM73A ,  ZNF273 ,  MGC50559 ,  GABARAP ,  ...

  • 38 genes correlated to 'PATHOLOGICSPREAD(M)'.

    • KCNC2 ,  TCF7 ,  HCN1 ,  C8ORF30A ,  SPACA3 ,  ...

  • 7398 genes correlated to 'TUMOR.STAGE'.

    • FGF18 ,  WT1 ,  KITLG ,  RBM38 ,  ELL2 ,  ...

  • 5782 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

    • CYP3A5 ,  CYP3A4 ,  CYP3A7 ,  TCF21 ,  MAP2K7 ,  ...

  • 2 genes correlated to 'STOPPEDSMOKINGYEAR'.

    • RAI14 ,  THBD

  • 9 genes correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.

    • PSME4 ,  C1ORF64 ,  LMNB2 ,  LONP1 ,  SLC25A1 ,  ...

  • 1 gene correlated to 'YEAROFTOBACCOSMOKINGONSET'.

    • MMP10

  • No genes correlated to '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=3019 shorter survival N=1360 longer survival N=1659
AGE Spearman correlation test N=3653 older N=1733 younger N=1920
PRIMARY SITE OF DISEASE ANOVA test N=17317        
GENDER t test N=9010 male N=4122 female N=4888
KARNOFSKY PERFORMANCE SCORE Spearman correlation test N=206 higher score N=129 lower score N=77
HISTOLOGICAL TYPE ANOVA test N=16612        
PATHOLOGY T Spearman correlation test N=5976 higher pT N=3211 lower pT N=2765
PATHOLOGY N Spearman correlation test N=15 higher pN N=3 lower pN N=12
PATHOLOGICSPREAD(M) ANOVA test N=38        
TUMOR STAGE Spearman correlation test N=7398 higher stage N=3999 lower stage N=3399
RADIATIONS RADIATION REGIMENINDICATION t test N=5782 yes N=2840 no N=2942
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
STOPPEDSMOKINGYEAR Spearman correlation test N=2 higher stoppedsmokingyear N=0 lower stoppedsmokingyear N=2
TOBACCOSMOKINGHISTORYINDICATOR ANOVA test N=9        
YEAROFTOBACCOSMOKINGONSET Spearman correlation test N=1 higher yearoftobaccosmokingonset N=0 lower yearoftobaccosmokingonset N=1
Clinical variable #1: 'Time to Death'

3019 genes related to 'Time to Death'.

Table S1.  Basic characteristics of clinical feature: 'Time to Death'

Time to Death Duration (Months) 0.1-223.4 (median=22.9)
  censored N = 1002
  death N = 437
     
  Significant markers N = 3019
  associated with shorter survival 1360
  associated with longer survival 1659
List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test

HazardRatio Wald_P Q C_index
KLHL14 1.26 0 0 0.6
ASS1 1.32 0 0 0.621
IGSF11 1.36 0 0 0.642
UPK1B 1.21 0 0 0.636
C4ORF32 0.77 0 0 0.38
ZRSR1 0.55 0 0 0.349
MDS1 1.37 0 0 0.621
GALNT12 1.31 0 0 0.615
MUC4 1.22 0 0 0.635
NUBP1 0.46 0 0 0.354

Figure S1.  Get High-res Image As an example, this figure shows the association of KLHL14 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 0 with univariate Cox regression analysis using continuous log-2 expression values.

Clinical variable #2: 'AGE'

3653 genes related to 'AGE'.

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

AGE Mean (SD) 61.37 (13)
  Significant markers N = 3653
  pos. correlated 1733
  neg. correlated 1920
List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S4.  Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

SpearmanCorr corrP Q
GREB1 -0.2872 2.183e-31 3.89e-27
COL18A1 -0.2769 3.26e-29 5.81e-25
DUOX2 0.2745 1.026e-28 1.83e-24
LDOC1 -0.2665 4.338e-27 7.73e-23
GALNTL1 -0.2664 4.433e-27 7.9e-23
OBSL1 -0.2639 1.357e-26 2.42e-22
CYP2C18 0.26 8.069e-26 1.44e-21
FOXF1 0.2597 9.212e-26 1.64e-21
BBOX1 -0.2563 3.983e-25 7.09e-21
SH3BP5 -0.2556 5.522e-25 9.83e-21

Figure S2.  Get High-res Image As an example, this figure shows the association of GREB1 to 'AGE'. P value = 2.18e-31 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'PRIMARY.SITE.OF.DISEASE'

17317 genes related to 'PRIMARY.SITE.OF.DISEASE'.

Table S5.  Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'

PRIMARY.SITE.OF.DISEASE Labels N
  BREAST 527
  COLON 154
  ENDOMETRIAL 54
  KIDNEY 72
  LUNG 186
  OMENTUM 2
  OVARY 529
  PERITONEUM (OVARY) 2
  RECTUM 68
     
  Significant markers N = 17317
List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

Table S6.  Get Full Table List of top 10 genes differentially expressed by 'PRIMARY.SITE.OF.DISEASE'

ANOVA_P Q
KLHL14 0 0
ZG16 0 0
SLC22A2 0 0
PDZD3 0 0
EMX2 0 0
NPR1 0 0
FUT4 0 0
ACF 0 0
FXYD2 0 0
UPK1B 0 0

Figure S3.  Get High-res Image As an example, this figure shows the association of KLHL14 to 'PRIMARY.SITE.OF.DISEASE'. P value = 0 with ANOVA analysis.

Clinical variable #4: 'GENDER'

9010 genes related to 'GENDER'.

Table S7.  Basic characteristics of clinical feature: 'GENDER'

GENDER Labels N
  FEMALE 1306
  MALE 290
     
  Significant markers N = 9010
  Higher in MALE 4122
  Higher in FEMALE 4888
List of top 10 genes differentially expressed by 'GENDER'

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

T(pos if higher in 'MALE') ttestP Q AUC
ESR1 -36.27 1.51e-167 2.69e-163 0.8779
RSPO1 -31.61 2.878e-167 5.13e-163 0.8495
DDX3Y 53.37 2.933e-164 5.22e-160 0.984
RPS4Y1 51.81 5.249e-156 9.35e-152 0.9718
EIF1AY 48.86 1.724e-151 3.07e-147 0.9839
ERBB4 -32.69 2.595e-148 4.62e-144 0.8588
RPS4Y2 48.57 3.701e-148 6.59e-144 0.9817
JARID1D 44.55 2.443e-147 4.35e-143 0.9762
SCGB2A2 -29.54 1.622e-146 2.89e-142 0.8579
CYORF15A 43.56 1.814e-139 3.23e-135 0.9813

Figure S4.  Get High-res Image As an example, this figure shows the association of ESR1 to 'GENDER'. P value = 1.51e-167 with T-test analysis.

Clinical variable #5: 'KARNOFSKY.PERFORMANCE.SCORE'

206 genes related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S9.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 60.22 (34)
  Significant markers N = 206
  pos. correlated 129
  neg. correlated 77
List of top 10 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

Table S10.  Get Full Table List of top 10 genes significantly correlated to 'KARNOFSKY.PERFORMANCE.SCORE' by Spearman correlation test

SpearmanCorr corrP Q
PPP1R9A 0.5916 4.259e-10 7.59e-06
VASN 0.5749 1.671e-09 2.98e-05
MARCH7 -0.5551 7.711e-09 0.000137
CCDC135 0.5548 7.875e-09 0.00014
POGZ 0.5503 1.102e-08 0.000196
INSIG2 -0.5485 1.255e-08 0.000223
ZNF503 0.5479 1.318e-08 0.000235
TLE1 0.5448 1.642e-08 0.000292
ADK -0.5439 1.761e-08 0.000314
PCYT1A -0.5421 1.996e-08 0.000355

Figure S5.  Get High-res Image As an example, this figure shows the association of PPP1R9A to 'KARNOFSKY.PERFORMANCE.SCORE'. P value = 4.26e-10 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #6: 'HISTOLOGICAL.TYPE'

16612 genes related to 'HISTOLOGICAL.TYPE'.

Table S11.  Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'

HISTOLOGICAL.TYPE Labels N
  COLON ADENOCARCINOMA 128
  COLON MUCINOUS ADENOCARCINOMA 24
  ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA 41
  KIDNEY CLEAR CELL RENAL CARCINOMA 72
  LUNG ADENOCARCINOMA MIXED SUBTYPE 1
  LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 30
  LUNG BASALOID SQUAMOUS CELL CARCINOMA 5
  LUNG CLEAR CELL ADENOCARCINOMA 1
  LUNG PAPILLARY SQUAMOUS CELL CARICNOMA 1
  LUNG SQUAMOUS CELL CARCINOMA- NOT OTHERWISE SPECIFIED (NOS) 148
  MIXED SEROUS AND ENDOMETRIOID 1
  RECTAL ADENOCARCINOMA 58
  RECTAL MUCINOUS ADENOCARCINOMA 7
  SEROUS CYSTADENOCARCINOMA 533
  SEROUS ENDOMETRIAL ADENOCARCINOMA 12
     
  Significant markers N = 16612
List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

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

ANOVA_P Q
KLHL14 0 0
EMX2 0 0
NPR1 0 0
FUT4 0 0
FXYD2 0 0
SPINK4 0 0
SLC12A2 0 0
CDH17 0 0
SATB2 0 0
OVOL2 0 0

Figure S6.  Get High-res Image As an example, this figure shows the association of KLHL14 to 'HISTOLOGICAL.TYPE'. P value = 0 with ANOVA analysis.

Clinical variable #7: 'PATHOLOGY.T'

5976 genes related to 'PATHOLOGY.T'.

Table S13.  Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T Mean (SD) 2.3 (0.85)
  N
  T1 92
  T2 179
  T3 180
  T4 29
     
  Significant markers N = 5976
  pos. correlated 3211
  neg. correlated 2765
List of top 10 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S14.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

SpearmanCorr corrP Q
C13ORF3 0.5223 5.902e-35 1.05e-30
NR3C1 -0.5197 1.446e-34 2.58e-30
CDCA7 0.5176 3.045e-34 5.42e-30
LIFR -0.5157 5.673e-34 1.01e-29
C20ORF151 0.5135 1.21e-33 2.15e-29
NOXO1 0.5086 6.106e-33 1.09e-28
PDSS1 0.5075 8.839e-33 1.57e-28
B3GNT3 0.5029 3.943e-32 7.02e-28
MAL -0.501 7.35e-32 1.31e-27
POF1B 0.5 9.967e-32 1.77e-27

Figure S7.  Get High-res Image As an example, this figure shows the association of C13ORF3 to 'PATHOLOGY.T'. P value = 5.9e-35 with Spearman correlation analysis.

Clinical variable #8: 'PATHOLOGY.N'

15 genes related to 'PATHOLOGY.N'.

Table S15.  Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N Mean (SD) 0.51 (0.77)
  N
  N0 291
  N1 90
  N2 61
  N3 5
     
  Significant markers N = 15
  pos. correlated 3
  neg. correlated 12
List of top 10 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

Table S16.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY.N' by Spearman correlation test

SpearmanCorr corrP Q
TNFRSF10C -0.2609 2.183e-08 0.000389
FAM73A -0.2572 3.495e-08 0.000623
ZNF273 0.2502 8.307e-08 0.00148
MGC50559 -0.2495 9.052e-08 0.00161
GABARAP -0.2459 1.402e-07 0.0025
LUZP2 0.2386 3.425e-07 0.0061
CNDP2 -0.2299 8.935e-07 0.0159
DHCR7 0.2289 9.976e-07 0.0178
IFIT3 -0.227 1.238e-06 0.022
DOCK8 -0.2269 1.255e-06 0.0223

Figure S8.  Get High-res Image As an example, this figure shows the association of TNFRSF10C to 'PATHOLOGY.N'. P value = 2.18e-08 with Spearman correlation analysis.

Clinical variable #9: 'PATHOLOGICSPREAD(M)'

38 genes related to 'PATHOLOGICSPREAD(M)'.

Table S17.  Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) Labels N
  M0 429
  M1 45
  M1A 1
     
  Significant markers N = 38
List of top 10 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

Table S18.  Get Full Table List of top 10 genes differentially expressed by 'PATHOLOGICSPREAD(M)'

ANOVA_P Q
KCNC2 1.128e-09 2.01e-05
TCF7 1.407e-08 0.000251
HCN1 2.323e-08 0.000414
C8ORF30A 7.324e-08 0.0013
SPACA3 1.123e-07 0.002
NPAS2 3.483e-07 0.0062
RBM26 4.027e-07 0.00717
SERPINA10 5.335e-07 0.0095
ACSL6 5.485e-07 0.00977
SERPINA4 6.236e-07 0.0111

Figure S9.  Get High-res Image As an example, this figure shows the association of KCNC2 to 'PATHOLOGICSPREAD(M)'. P value = 1.13e-09 with ANOVA analysis.

Clinical variable #10: 'TUMOR.STAGE'

7398 genes related to 'TUMOR.STAGE'.

Table S19.  Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE Mean (SD) 2.55 (0.95)
  N
  Stage 1 206
  Stage 2 164
  Stage 3 512
  Stage 4 121
     
  Significant markers N = 7398
  pos. correlated 3999
  neg. correlated 3399
List of top 10 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

Table S20.  Get Full Table List of top 10 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test

SpearmanCorr corrP Q
FGF18 0.5194 2.226e-70 3.97e-66
WT1 0.5082 5.859e-67 1.04e-62
KITLG -0.492 2.849e-62 5.07e-58
RBM38 0.4868 8.662e-61 1.54e-56
ELL2 -0.4839 5.194e-60 9.25e-56
ZNF503 0.4802 5.577e-59 9.93e-55
DOK7 0.4801 5.994e-59 1.07e-54
RIMS4 0.479 1.141e-58 2.03e-54
KLK8 0.4787 1.387e-58 2.47e-54
KLK6 0.4783 1.813e-58 3.23e-54

Figure S10.  Get High-res Image As an example, this figure shows the association of FGF18 to 'TUMOR.STAGE'. P value = 2.23e-70 with Spearman correlation analysis.

Clinical variable #11: 'RADIATIONS.RADIATION.REGIMENINDICATION'

5782 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S21.  Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION Labels N
  NO 179
  YES 1417
     
  Significant markers N = 5782
  Higher in YES 2840
  Higher in NO 2942
List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S22.  Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

T(pos if higher in 'YES') ttestP Q AUC
CYP3A5 22.7 4.323e-80 7.7e-76 0.7907
CYP3A4 20.54 1.628e-69 2.9e-65 0.7756
CYP3A7 20.59 2.004e-69 3.57e-65 0.7658
TCF21 20.96 4.673e-65 8.32e-61 0.7936
MAP2K7 21.19 3.772e-64 6.72e-60 0.8081
AADAC 20.16 1.321e-63 2.35e-59 0.7729
CCDC71 21.09 5.535e-62 9.86e-58 0.8178
REG1A 19.04 1.242e-58 2.21e-54 0.7736
PDZD3 17.14 1.39e-57 2.47e-53 0.6829
CHMP4B 20.01 1.954e-57 3.48e-53 0.8095

Figure S11.  Get High-res Image As an example, this figure shows the association of CYP3A5 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 4.32e-80 with T-test analysis.

Clinical variable #12: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S23.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 53.05 (35)
  Significant markers N = 0
Clinical variable #13: 'STOPPEDSMOKINGYEAR'

2 genes related to 'STOPPEDSMOKINGYEAR'.

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

STOPPEDSMOKINGYEAR Mean (SD) 1996.98 (12)
  Significant markers N = 2
  pos. correlated 0
  neg. correlated 2
List of 2 genes significantly correlated to 'STOPPEDSMOKINGYEAR' by Spearman correlation test

Table S25.  Get Full Table List of 2 genes significantly correlated to 'STOPPEDSMOKINGYEAR' by Spearman correlation test

SpearmanCorr corrP Q
RAI14 -0.4114 1.704e-06 0.0304
THBD -0.4082 2.083e-06 0.0371

Figure S12.  Get High-res Image As an example, this figure shows the association of RAI14 to 'STOPPEDSMOKINGYEAR'. P value = 1.7e-06 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #14: 'TOBACCOSMOKINGHISTORYINDICATOR'

9 genes related to 'TOBACCOSMOKINGHISTORYINDICATOR'.

Table S26.  Basic characteristics of clinical feature: 'TOBACCOSMOKINGHISTORYINDICATOR'

TOBACCOSMOKINGHISTORYINDICATOR Labels N
  CURRENT REFORMED SMOKER FOR < OR = 15 YEARS 93
  CURRENT REFORMED SMOKER FOR > 15 YEARS 49
  CURRENT SMOKER 31
  LIFELONG NON-SMOKER 11
     
  Significant markers N = 9
List of 9 genes differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

Table S27.  Get Full Table List of 9 genes differentially expressed by 'TOBACCOSMOKINGHISTORYINDICATOR'

ANOVA_P Q
PSME4 6.816e-08 0.00121
C1ORF64 1.645e-07 0.00293
LMNB2 1.211e-06 0.0216
LONP1 1.573e-06 0.028
SLC25A1 1.62e-06 0.0289
IGFBP7 1.965e-06 0.035
N6AMT2 2.361e-06 0.0421
CATSPER3 2.469e-06 0.044
LAS1L 2.63e-06 0.0468

Figure S13.  Get High-res Image As an example, this figure shows the association of PSME4 to 'TOBACCOSMOKINGHISTORYINDICATOR'. P value = 6.82e-08 with ANOVA analysis.

Clinical variable #15: 'YEAROFTOBACCOSMOKINGONSET'

One gene related to 'YEAROFTOBACCOSMOKINGONSET'.

Table S28.  Basic characteristics of clinical feature: 'YEAROFTOBACCOSMOKINGONSET'

YEAROFTOBACCOSMOKINGONSET Mean (SD) 1959.74 (11)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one gene significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

Table S29.  Get Full Table List of one gene significantly correlated to 'YEAROFTOBACCOSMOKINGONSET' by Spearman correlation test

SpearmanCorr corrP Q
MMP10 -0.4473 4.812e-07 0.00857

Figure S14.  Get High-res Image As an example, this figure shows the association of MMP10 to 'YEAROFTOBACCOSMOKINGONSET'. P value = 4.81e-07 with Spearman correlation analysis. The straight line presents the best linear regression.

Methods & Data
Input

  • Expresson data file = PANCAN12-TP.medianexp.txt

  • Clinical data file = PANCAN12-TP.clin.merged.picked.txt

  • Number of patients = 1596

  • Number of genes = 17814

  • Number of clinical features = 15

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.

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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