Correlation between mRNAseq expression and clinical features
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C1WW7H0Z
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between mRNAseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1WW7H0Z
Overview
Introduction

This pipeline uses various statistical tests to identify mRNAs whose log2 expression levels correlated to selected clinical features. The input file "CESC-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt" is generated in the pipeline mRNAseq_Preprocess in the stddata run.

Summary

Testing the association between 18187 genes and 39 clinical features across 304 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 23 clinical features related to at least one genes.

  • 30 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • EAF2|55840 ,  SSBP3|23648 ,  NCAPH2|29781 ,  PRSS36|146547 ,  CXORF42|158801 ,  ...

  • 30 genes correlated to 'YEARS_TO_BIRTH'.

    • NXNL2|158046 ,  LANCL1|10314 ,  CORO6|84940 ,  PGR|5241 ,  RHOF|54509 ,  ...

  • 30 genes correlated to 'PATHOLOGY_T_STAGE'.

    • FBXL18|80028 ,  CYB561D1|284613 ,  TRIM25|7706 ,  PPFIA4|8497 ,  TMEM220|388335 ,  ...

  • 1 gene correlated to 'PATHOLOGY_M_STAGE'.

    • ZFAND6|54469

  • 30 genes correlated to 'RADIATION_THERAPY'.

    • EXOSC9|5393 ,  HADH|3033 ,  LHX4|89884 ,  PAG1|55824 ,  HNRNPD|3184 ,  ...

  • 30 genes correlated to 'HISTOLOGICAL_TYPE'.

    • TP63|8626 ,  DDAH1|23576 ,  C3ORF54|389119 ,  BICD2|23299 ,  EPCAM|4072 ,  ...

  • 30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

    • KLRG2|346689 ,  FLJ35390|255031 ,  TMPRSS3|64699 ,  A2ML1|144568 ,  APC2|10297 ,  ...

  • 6 genes correlated to 'RACE'.

    • XKR9|389668 ,  LOC90784|90784 ,  POM121L10P|646074 ,  RNF112|7732 ,  DLX3|1747 ,  ...

  • 30 genes correlated to 'WEIGHT_KG_AT_DIAGNOSIS'.

    • BLOC1S1|2647 ,  IL17RA|23765 ,  NUBP1|4682 ,  GNRHR2|114814 ,  IK|3550 ,  ...

  • 30 genes correlated to 'TUMOR_STATUS'.

    • S1PR4|8698 ,  SOCS5|9655 ,  IFI30|10437 ,  RHOH|399 ,  MPND|84954 ,  ...

  • 30 genes correlated to 'NEOPLASM_HISTOLOGIC_GRADE'.

    • ABLIM1|3983 ,  FUT2|2524 ,  FUT6|2528 ,  CDS1|1040 ,  CLINT1|9685 ,  ...

  • 30 genes correlated to 'TOBACCO_SMOKING_HISTORY'.

    • GPR15|2838 ,  LRRC8A|56262 ,  C1ORF127|148345 ,  GPBAR1|151306 ,  HSD3B7|80270 ,  ...

  • 1 gene correlated to 'AGEBEGANSMOKINGINYEARS'.

    • GAD1|2571

  • 30 genes correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

    • ENPP3|5169 ,  RPL19P12|100129424 ,  SDCBP|6386 ,  FLJ44635|392490 ,  FAM35B2|439965 ,  ...

  • 30 genes correlated to 'MENOPAUSE_STATUS'.

    • RIMBP3|85376 ,  RIMBP3C|150221 ,  RARB|5915 ,  RPF1|80135 ,  C1ORF52|148423 ,  ...

  • 7 genes correlated to 'LYMPHOVASCULAR_INVOLVEMENT'.

    • TBCE|6905 ,  EXOG|9941 ,  MRPL30|51263 ,  LOC255167|255167 ,  SUSD4|55061 ,  ...

  • 30 genes correlated to 'LYMPH_NODES_EXAMINED_HE_COUNT'.

    • KLRG2|346689 ,  FLJ35390|255031 ,  TMPRSS3|64699 ,  A2ML1|144568 ,  APC2|10297 ,  ...

  • 30 genes correlated to 'KERATINIZATION_SQUAMOUS_CELL'.

    • QKI|9444 ,  SYT17|51760 ,  MAP7D3|79649 ,  SPG7|6687 ,  C9ORF30|91283 ,  ...

  • 30 genes correlated to 'INITIAL_PATHOLOGIC_DX_YEAR'.

    • ?|390284 ,  RPPH1|85495 ,  SNAPC5|10302 ,  C19ORF33|64073 ,  POM121L8P|29797 ,  ...

  • 30 genes correlated to 'HEIGHT_CM_AT_DIAGNOSIS'.

    • RRAD|6236 ,  C19ORF33|64073 ,  ZNF107|51427 ,  ?|390284 ,  FOSB|2354 ,  ...

  • 1 gene correlated to 'CERVIX_SUV_RESULTS'.

    • HDHD1A|8226

  • 30 genes correlated to 'AGE_AT_DIAGNOSIS'.

    • NXNL2|158046 ,  PGR|5241 ,  RHOF|54509 ,  CORO6|84940 ,  GPR97|222487 ,  ...

  • 30 genes correlated to 'CLINICAL_STAGE'.

    • TRIM25|7706 ,  FBXL18|80028 ,  RGS1|5996 ,  ZC3HAV1|56829 ,  PPFIA4|8497 ,  ...

  • No genes correlated to 'PATHOLOGY_N_STAGE', 'NUMBER_PACK_YEARS_SMOKED', 'ETHNICITY', 'TOBACCO_SMOKING_YEAR_STOPPED', 'TOBACCO_SMOKING_PACK_YEARS_SMOKED', 'RADIATION_THERAPY_STATUS', 'PREGNANCIES_COUNT_TOTAL', 'PREGNANCIES_COUNT_STILLBIRTH', 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT', 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT', 'PREGNANCIES_COUNT_ECTOPIC', 'POS_LYMPH_NODE_LOCATION', 'LYMPH_NODES_EXAMINED', 'HISTORY_HORMONAL_CONTRACEPTIVES_USE', 'CORPUS_INVOLVEMENT', and 'CHEMO_CONCURRENT_TYPE'.

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
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test N=30   N=NA   N=NA
YEARS_TO_BIRTH Spearman correlation test N=30 older N=15 younger N=15
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=17 lower stage N=13
PATHOLOGY_N_STAGE Wilcoxon test   N=0        
PATHOLOGY_M_STAGE Wilcoxon test N=1 class1 N=1 class0 N=0
RADIATION_THERAPY Wilcoxon test N=30 yes N=30 no N=0
HISTOLOGICAL_TYPE Kruskal-Wallis test N=30        
NUMBER_PACK_YEARS_SMOKED Spearman correlation test   N=0        
NUMBER_OF_LYMPH_NODES Spearman correlation test N=30 higher number_of_lymph_nodes N=19 lower number_of_lymph_nodes N=11
RACE Kruskal-Wallis test N=6        
ETHNICITY Wilcoxon test   N=0        
WEIGHT_KG_AT_DIAGNOSIS Spearman correlation test N=30 higher weight_kg_at_diagnosis N=22 lower weight_kg_at_diagnosis N=8
TUMOR_STATUS Wilcoxon test N=30 with tumor N=30 tumor free N=0
NEOPLASM_HISTOLOGIC_GRADE Kruskal-Wallis test N=30        
TOBACCO_SMOKING_YEAR_STOPPED Spearman correlation test   N=0        
TOBACCO_SMOKING_PACK_YEARS_SMOKED Spearman correlation test   N=0        
TOBACCO_SMOKING_HISTORY Spearman correlation test N=30 higher tobacco_smoking_history N=16 lower tobacco_smoking_history N=14
AGEBEGANSMOKINGINYEARS Spearman correlation test N=1 higher agebegansmokinginyears N=1 lower agebegansmokinginyears N=0
RADIATION_THERAPY_STATUS Wilcoxon test   N=0        
PREGNANCIES_COUNT_TOTAL Spearman correlation test   N=0        
PREGNANCIES_COUNT_STILLBIRTH Spearman correlation test   N=0        
PREGNANCY_SPONTANEOUS_ABORTION_COUNT Spearman correlation test   N=0        
PREGNANCIES_COUNT_LIVE_BIRTH Spearman correlation test N=30 higher pregnancies_count_live_birth N=5 lower pregnancies_count_live_birth N=25
PREGNANCY_THERAPEUTIC_ABORTION_COUNT Spearman correlation test   N=0        
PREGNANCIES_COUNT_ECTOPIC Spearman correlation test   N=0        
POS_LYMPH_NODE_LOCATION Kruskal-Wallis test   N=0        
MENOPAUSE_STATUS Kruskal-Wallis test N=30        
LYMPHOVASCULAR_INVOLVEMENT Wilcoxon test N=7 present N=7 absent N=0
LYMPH_NODES_EXAMINED_HE_COUNT Spearman correlation test N=30 higher lymph_nodes_examined_he_count N=19 lower lymph_nodes_examined_he_count N=11
LYMPH_NODES_EXAMINED Spearman correlation test   N=0        
KERATINIZATION_SQUAMOUS_CELL Wilcoxon test N=30 non-keratinizing squamous cell carcinoma N=30 keratinizing squamous cell carcinoma N=0
INITIAL_PATHOLOGIC_DX_YEAR Spearman correlation test N=30 higher initial_pathologic_dx_year N=10 lower initial_pathologic_dx_year N=20
HISTORY_HORMONAL_CONTRACEPTIVES_USE Kruskal-Wallis test   N=0        
HEIGHT_CM_AT_DIAGNOSIS Spearman correlation test N=30 higher height_cm_at_diagnosis N=20 lower height_cm_at_diagnosis N=10
CORPUS_INVOLVEMENT Wilcoxon test   N=0        
CHEMO_CONCURRENT_TYPE Kruskal-Wallis test   N=0        
CERVIX_SUV_RESULTS Spearman correlation test N=1 higher cervix_suv_results N=1 lower cervix_suv_results N=0
AGE_AT_DIAGNOSIS Spearman correlation test N=30 higher age_at_diagnosis N=15 lower age_at_diagnosis N=15
CLINICAL_STAGE Kruskal-Wallis test N=30        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

30 genes related to 'DAYS_TO_DEATH_OR_LAST_FUP'.

Table S1.  Basic characteristics of clinical feature: 'DAYS_TO_DEATH_OR_LAST_FUP'

DAYS_TO_DEATH_OR_LAST_FUP Duration (Months) 0.1-210.7 (median=23.2)
  censored N = 231
  death N = 72
     
  Significant markers N = 30
  associated with shorter survival NA
  associated with longer survival NA
List of top 10 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 genes significantly associated with 'Time to Death' by Cox regression test. For the survival curves, it compared quantile intervals at c(0, 0.25, 0.50, 0.75, 1) and did not try survival analysis if there is only one interval.

logrank_P Q C_index
EAF2|55840 2.42e-06 0.03 0.328
SSBP3|23648 3.99e-06 0.03 0.313
NCAPH2|29781 6.79e-06 0.03 0.358
PRSS36|146547 8.5e-06 0.03 0.304
CXORF42|158801 9.57e-06 0.03 0.331
TTC16|158248 1.14e-05 0.03 0.378
P4HA1|5033 1.19e-05 0.03 0.666
TREX1|11277 1.41e-05 0.03 0.311
GATS|352954 1.51e-05 0.03 0.318
ESM1|11082 2.01e-05 0.037 0.67
Clinical variable #2: 'YEARS_TO_BIRTH'

30 genes related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 48.16 (14)
  Significant markers N = 30
  pos. correlated 15
  neg. correlated 15
List of top 10 genes differentially expressed by 'YEARS_TO_BIRTH'

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

SpearmanCorr corrP Q
NXNL2|158046 -0.3781 7.084e-11 1.29e-06
LANCL1|10314 0.3204 1.225e-08 0.000111
CORO6|84940 -0.3165 1.888e-08 0.000114
PGR|5241 -0.3142 2.534e-08 0.000115
RHOF|54509 -0.3088 4.299e-08 0.000152
IL24|11009 -0.3104 5.21e-08 0.000152
CSF3|1440 -0.3086 6.975e-08 0.000152
GALNT11|63917 0.3033 7.647e-08 0.000152
DIO2|1734 -0.3019 8.821e-08 0.000152
GPR97|222487 -0.3018 8.929e-08 0.000152
Clinical variable #3: 'PATHOLOGY_T_STAGE'

30 genes related to 'PATHOLOGY_T_STAGE'.

Table S5.  Basic characteristics of clinical feature: 'PATHOLOGY_T_STAGE'

PATHOLOGY_T_STAGE Mean (SD) 1.59 (0.81)
  N
  T1 140
  T2 71
  T3 20
  T4 10
     
  Significant markers N = 30
  pos. correlated 17
  neg. correlated 13
List of top 10 genes differentially expressed by 'PATHOLOGY_T_STAGE'

Table S6.  Get Full Table List of top 10 genes significantly correlated to 'PATHOLOGY_T_STAGE' by Spearman correlation test

SpearmanCorr corrP Q
FBXL18|80028 0.3693 3.346e-09 6.09e-05
CYB561D1|284613 0.351 2.136e-08 0.00019
TRIM25|7706 0.3447 3.97e-08 0.00019
PPFIA4|8497 0.3432 4.577e-08 0.00019
TMEM220|388335 -0.3418 5.215e-08 0.00019
ZC3HAV1|56829 0.3293 1.674e-07 0.000507
ZNF487|642819 -0.3115 8.985e-07 0.00233
CCNF|899 0.3086 1.033e-06 0.00235
CIR1|9541 -0.2999 2.134e-06 0.00428
PPIG|9360 -0.2987 2.352e-06 0.00428
Clinical variable #4: 'PATHOLOGY_N_STAGE'

No gene related to 'PATHOLOGY_N_STAGE'.

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

PATHOLOGY_N_STAGE Labels N
  N0 133
  N1 60
     
  Significant markers N = 0
Clinical variable #5: 'PATHOLOGY_M_STAGE'

One gene related to 'PATHOLOGY_M_STAGE'.

Table S8.  Basic characteristics of clinical feature: 'PATHOLOGY_M_STAGE'

PATHOLOGY_M_STAGE Labels N
  class0 116
  class1 10
     
  Significant markers N = 1
  Higher in class1 1
  Higher in class0 0
List of one gene differentially expressed by 'PATHOLOGY_M_STAGE'

Table S9.  Get Full Table List of one gene differentially expressed by 'PATHOLOGY_M_STAGE'

W(pos if higher in 'class1') wilcoxontestP Q AUC
ZFAND6|54469 94 1.177e-05 0.214 0.919
Clinical variable #6: 'RADIATION_THERAPY'

30 genes related to 'RADIATION_THERAPY'.

Table S10.  Basic characteristics of clinical feature: 'RADIATION_THERAPY'

RADIATION_THERAPY Labels N
  NO 55
  YES 127
     
  Significant markers N = 30
  Higher in YES 30
  Higher in NO 0
List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

Table S11.  Get Full Table List of top 10 genes differentially expressed by 'RADIATION_THERAPY'

W(pos if higher in 'YES') wilcoxontestP Q AUC
EXOSC9|5393 2007 5.365e-06 0.0651 0.7127
HADH|3033 2062 1.179e-05 0.0651 0.7048
LHX4|89884 4536 1.26e-05 0.0651 0.7092
PAG1|55824 4907 1.475e-05 0.0651 0.7025
HNRNPD|3184 2092 1.791e-05 0.0651 0.7005
H3F3C|440093 2113 2.387e-05 0.0724 0.6975
ZNFX1|57169 4842 3.576e-05 0.0786 0.6932
DPH3B|100132911 4678 4.252e-05 0.0786 0.693
AIMP1|9255 2157 4.307e-05 0.0786 0.6912
CCDC111|201973 2167 4.913e-05 0.0786 0.6898
Clinical variable #7: 'HISTOLOGICAL_TYPE'

30 genes related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  ADENOSQUAMOUS 5
  CERVICAL SQUAMOUS CELL CARCINOMA 252
  ENDOCERVICAL ADENOCARCINOMA OF THE USUAL TYPE 6
  ENDOCERVICAL TYPE OF ADENOCARCINOMA 21
  ENDOMETRIOID ADENOCARCINOMA OF ENDOCERVIX 3
  MUCINOUS ADENOCARCINOMA OF ENDOCERVICAL TYPE 17
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

Table S13.  Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
TP63|8626 6.172e-23 1.12e-18
DDAH1|23576 1.488e-22 1.35e-18
C3ORF54|389119 2.221e-22 1.35e-18
BICD2|23299 3.995e-22 1.62e-18
EPCAM|4072 4.44e-22 1.62e-18
CLCA2|9635 5.404e-22 1.64e-18
CLDN3|1365 7.534e-22 1.96e-18
GPR87|53836 1.292e-21 2.59e-18
KRT6A|3853 1.344e-21 2.59e-18
CSTA|1475 1.422e-21 2.59e-18
Clinical variable #8: 'NUMBER_PACK_YEARS_SMOKED'

No gene related to 'NUMBER_PACK_YEARS_SMOKED'.

Table S14.  Basic characteristics of clinical feature: 'NUMBER_PACK_YEARS_SMOKED'

NUMBER_PACK_YEARS_SMOKED Mean (SD) 17.38 (14)
  Significant markers N = 0
Clinical variable #9: 'NUMBER_OF_LYMPH_NODES'

30 genes related to 'NUMBER_OF_LYMPH_NODES'.

Table S15.  Basic characteristics of clinical feature: 'NUMBER_OF_LYMPH_NODES'

NUMBER_OF_LYMPH_NODES Mean (SD) 1.04 (2.4)
  Significant markers N = 30
  pos. correlated 19
  neg. correlated 11
List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

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

SpearmanCorr corrP Q
KLRG2|346689 0.3296 2.492e-05 0.124
FLJ35390|255031 0.3219 3.499e-05 0.124
TMPRSS3|64699 -0.3192 4.115e-05 0.124
A2ML1|144568 0.3207 4.234e-05 0.124
APC2|10297 0.3192 4.358e-05 0.124
SERPINB12|89777 0.3899 4.668e-05 0.124
METTL8|79828 0.3154 5.133e-05 0.124
NOTCH1|4851 0.3119 6.274e-05 0.124
NCAM2|4685 0.3275 7.365e-05 0.124
PHC2|1912 -0.3089 7.447e-05 0.124
Clinical variable #10: 'RACE'

6 genes related to 'RACE'.

Table S17.  Basic characteristics of clinical feature: 'RACE'

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 7
  ASIAN 20
  BLACK OR AFRICAN AMERICAN 30
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 2
  WHITE 209
     
  Significant markers N = 6
List of 6 genes differentially expressed by 'RACE'

Table S18.  Get Full Table List of 6 genes differentially expressed by 'RACE'

kruskal_wallis_P Q
XKR9|389668 1.623e-06 0.0295
LOC90784|90784 3.317e-06 0.0302
POM121L10P|646074 8.024e-06 0.0486
RNF112|7732 1.518e-05 0.069
DLX3|1747 2.571e-05 0.0935
RPS26|6231 6.376e-05 0.193
Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 24
  NOT HISPANIC OR LATINO 169
     
  Significant markers N = 0
Clinical variable #12: 'WEIGHT_KG_AT_DIAGNOSIS'

30 genes related to 'WEIGHT_KG_AT_DIAGNOSIS'.

Table S20.  Basic characteristics of clinical feature: 'WEIGHT_KG_AT_DIAGNOSIS'

WEIGHT_KG_AT_DIAGNOSIS Mean (SD) 72.85 (22)
  Significant markers N = 30
  pos. correlated 22
  neg. correlated 8
List of top 10 genes differentially expressed by 'WEIGHT_KG_AT_DIAGNOSIS'

Table S21.  Get Full Table List of top 10 genes significantly correlated to 'WEIGHT_KG_AT_DIAGNOSIS' by Spearman correlation test

SpearmanCorr corrP Q
BLOC1S1|2647 0.3168 7.906e-08 0.00144
IL17RA|23765 -0.2979 4.828e-07 0.00439
NUBP1|4682 0.2931 7.486e-07 0.00454
GNRHR2|114814 0.2873 1.262e-06 0.00574
IK|3550 0.2846 1.609e-06 0.00585
TTPAL|79183 -0.2824 1.947e-06 0.0059
ZRSR2|8233 0.2796 2.478e-06 0.0061
SERINC3|10955 -0.2787 2.684e-06 0.0061
NASP|4678 0.2734 4.191e-06 0.00847
NCKAP1|10787 -0.2704 5.403e-06 0.00983
Clinical variable #13: 'TUMOR_STATUS'

30 genes related to 'TUMOR_STATUS'.

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

TUMOR_STATUS Labels N
  TUMOR FREE 198
  WITH TUMOR 80
     
  Significant markers N = 30
  Higher in WITH TUMOR 30
  Higher in TUMOR FREE 0
List of top 10 genes differentially expressed by 'TUMOR_STATUS'

Table S23.  Get Full Table List of top 10 genes differentially expressed by 'TUMOR_STATUS'

W(pos if higher in 'WITH TUMOR') wilcoxontestP Q AUC
S1PR4|8698 4798 2.694e-07 0.00478 0.6971
SOCS5|9655 10960 5.484e-07 0.00478 0.6919
IFI30|10437 4954 1.026e-06 0.00478 0.6872
RHOH|399 4957 1.052e-06 0.00478 0.6871
MPND|84954 5027 1.876e-06 0.00682 0.6826
ZBTB32|27033 4990 4.767e-06 0.00791 0.6769
CD6|923 5162 5.523e-06 0.00791 0.6741
SELPLG|6404 5167 5.743e-06 0.00791 0.6738
LCK|3932 5168 5.788e-06 0.00791 0.6737
CXCR6|10663 5170 5.879e-06 0.00791 0.6736
Clinical variable #14: 'NEOPLASM_HISTOLOGIC_GRADE'

30 genes related to 'NEOPLASM_HISTOLOGIC_GRADE'.

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

NEOPLASM_HISTOLOGIC_GRADE Labels N
  G1 18
  G2 135
  G3 118
  G4 1
  GX 24
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

Table S25.  Get Full Table List of top 10 genes differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

kruskal_wallis_P Q
ABLIM1|3983 2.427e-07 0.00437
FUT2|2524 6.054e-07 0.00437
FUT6|2528 7.207e-07 0.00437
CDS1|1040 3.937e-06 0.0179
CLINT1|9685 7.02e-06 0.0205
ARHGEF37|389337 7.164e-06 0.0205
WDR70|55100 7.898e-06 0.0205
SOHLH2|54937 1.135e-05 0.0236
FAHD2B|151313 1.168e-05 0.0236
SCARNA2|677766 1.69e-05 0.0307
Clinical variable #15: 'TOBACCO_SMOKING_YEAR_STOPPED'

No gene related to 'TOBACCO_SMOKING_YEAR_STOPPED'.

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

TOBACCO_SMOKING_YEAR_STOPPED Mean (SD) 1999.7 (14)
  Significant markers N = 0
Clinical variable #16: 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'

No gene related to 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'.

Table S27.  Basic characteristics of clinical feature: 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'

TOBACCO_SMOKING_PACK_YEARS_SMOKED Mean (SD) 17.38 (14)
  Significant markers N = 0
Clinical variable #17: 'TOBACCO_SMOKING_HISTORY'

30 genes related to 'TOBACCO_SMOKING_HISTORY'.

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

TOBACCO_SMOKING_HISTORY Mean (SD) 1.84 (1.1)
  Value N
  1 144
  2 64
  3 9
  4 40
  5 4
     
  Significant markers N = 30
  pos. correlated 16
  neg. correlated 14
List of top 10 genes differentially expressed by 'TOBACCO_SMOKING_HISTORY'

Table S29.  Get Full Table List of top 10 genes significantly correlated to 'TOBACCO_SMOKING_HISTORY' by Spearman correlation test

SpearmanCorr corrP Q
GPR15|2838 0.3318 2.293e-06 0.0417
LRRC8A|56262 0.2734 7.422e-06 0.0675
C1ORF127|148345 -0.2467 6.198e-05 0.293
GPBAR1|151306 -0.2425 7.551e-05 0.293
HSD3B7|80270 -0.2396 9.282e-05 0.293
RLF|6018 0.2309 0.0001674 0.293
REV1|51455 0.2305 0.0001722 0.293
SPEN|23013 0.2297 0.0001813 0.293
ZNF69|7620 -0.2298 0.0001858 0.293
SERPINB5|5268 0.2293 0.0001868 0.293
Clinical variable #18: 'AGEBEGANSMOKINGINYEARS'

One gene related to 'AGEBEGANSMOKINGINYEARS'.

Table S30.  Basic characteristics of clinical feature: 'AGEBEGANSMOKINGINYEARS'

AGEBEGANSMOKINGINYEARS Mean (SD) 21.14 (7.7)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene differentially expressed by 'AGEBEGANSMOKINGINYEARS'

Table S31.  Get Full Table List of one gene significantly correlated to 'AGEBEGANSMOKINGINYEARS' by Spearman correlation test

SpearmanCorr corrP Q
GAD1|2571 0.469 5.977e-06 0.109
Clinical variable #19: 'RADIATION_THERAPY_STATUS'

No gene related to 'RADIATION_THERAPY_STATUS'.

Table S32.  Basic characteristics of clinical feature: 'RADIATION_THERAPY_STATUS'

RADIATION_THERAPY_STATUS Labels N
  COMPLETED AS PLANNED 29
  TREATMENT NOT COMPLETED 3
     
  Significant markers N = 0
Clinical variable #20: 'PREGNANCIES_COUNT_TOTAL'

No gene related to 'PREGNANCIES_COUNT_TOTAL'.

Table S33.  Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_TOTAL'

PREGNANCIES_COUNT_TOTAL Mean (SD) 3.64 (2.6)
  Significant markers N = 0
Clinical variable #21: 'PREGNANCIES_COUNT_STILLBIRTH'

No gene related to 'PREGNANCIES_COUNT_STILLBIRTH'.

Table S34.  Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_STILLBIRTH'

PREGNANCIES_COUNT_STILLBIRTH Mean (SD) 0.07 (0.35)
  Value N
  0 106
  1 5
  3 1
     
  Significant markers N = 0
Clinical variable #22: 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'

No gene related to 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'.

Table S35.  Basic characteristics of clinical feature: 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'

PREGNANCY_SPONTANEOUS_ABORTION_COUNT Mean (SD) 0.54 (0.95)
  Significant markers N = 0
Clinical variable #23: 'PREGNANCIES_COUNT_LIVE_BIRTH'

30 genes related to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

Table S36.  Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_LIVE_BIRTH'

PREGNANCIES_COUNT_LIVE_BIRTH Mean (SD) 2.85 (2.1)
  Significant markers N = 30
  pos. correlated 5
  neg. correlated 25
List of top 10 genes differentially expressed by 'PREGNANCIES_COUNT_LIVE_BIRTH'

Table S37.  Get Full Table List of top 10 genes significantly correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
ENPP3|5169 -0.2737 2.894e-05 0.195
RPL19P12|100129424 -0.255 3.178e-05 0.195
SDCBP|6386 -0.2473 5.564e-05 0.195
FLJ44635|392490 -0.2452 6.442e-05 0.195
FAM35B2|439965 -0.2438 7.129e-05 0.195
POU2F1|5451 -0.2435 7.247e-05 0.195
HSP90B3P|343477 -0.2373 0.0001118 0.195
SLC43A1|8501 -0.2346 0.0001344 0.195
C10ORF79|80217 -0.2368 0.0001347 0.195
FANCG|2189 0.2339 0.0001414 0.195
Clinical variable #24: 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'

No gene related to 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'.

Table S38.  Basic characteristics of clinical feature: 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'

PREGNANCY_THERAPEUTIC_ABORTION_COUNT Mean (SD) 0.85 (1.8)
  Significant markers N = 0
Clinical variable #25: 'PREGNANCIES_COUNT_ECTOPIC'

No gene related to 'PREGNANCIES_COUNT_ECTOPIC'.

Table S39.  Basic characteristics of clinical feature: 'PREGNANCIES_COUNT_ECTOPIC'

PREGNANCIES_COUNT_ECTOPIC Mean (SD) 0.11 (0.34)
  Value N
  0 104
  1 11
  2 1
     
  Significant markers N = 0
Clinical variable #26: 'POS_LYMPH_NODE_LOCATION'

No gene related to 'POS_LYMPH_NODE_LOCATION'.

Table S40.  Basic characteristics of clinical feature: 'POS_LYMPH_NODE_LOCATION'

POS_LYMPH_NODE_LOCATION Labels N
  MACROSCOPIC PARAMETRIAL INVOLVEMENT 2
  MICROSCOPIC PARAMETRIAL INVOLVEMENT 8
  OTHER LOCATION, SPECIFY 40
  POSITIVE BLADDER MARGIN 1
  POSITIVE VAGINAL MARGIN 12
     
  Significant markers N = 0
Clinical variable #27: 'MENOPAUSE_STATUS'

30 genes related to 'MENOPAUSE_STATUS'.

Table S41.  Basic characteristics of clinical feature: 'MENOPAUSE_STATUS'

MENOPAUSE_STATUS Labels N
  INDETERMINATE (NEITHER PRE OR POSTMENOPAUSAL) 3
  PERI (6-12 MONTHS SINCE LAST MENSTRUAL PERIOD) 25
  POST (PRIOR BILATERAL OVARIECTOMY OR >12 MO SINCE LMP WITH NO PRIOR HYSTERECTOMY) 82
  PRE (<6 MONTHS SINCE LMP AND NO PRIOR BILATERAL OVARIECTOMY AND NOT ON ESTROGEN REPLACEMENT) 124
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'MENOPAUSE_STATUS'

Table S42.  Get Full Table List of top 10 genes differentially expressed by 'MENOPAUSE_STATUS'

kruskal_wallis_P Q
RIMBP3|85376 1.115e-07 0.00203
RIMBP3C|150221 2.869e-06 0.0219
RARB|5915 3.608e-06 0.0219
RPF1|80135 1.121e-05 0.0492
C1ORF52|148423 1.352e-05 0.0492
DIO2|1734 1.756e-05 0.0532
PGR|5241 3.059e-05 0.0795
HSFX2|100130086 3.773e-05 0.0858
PPIH|10465 4.843e-05 0.0886
PHGDH|26227 4.873e-05 0.0886
Clinical variable #28: 'LYMPHOVASCULAR_INVOLVEMENT'

7 genes related to 'LYMPHOVASCULAR_INVOLVEMENT'.

Table S43.  Basic characteristics of clinical feature: 'LYMPHOVASCULAR_INVOLVEMENT'

LYMPHOVASCULAR_INVOLVEMENT Labels N
  ABSENT 71
  PRESENT 79
     
  Significant markers N = 7
  Higher in PRESENT 7
  Higher in ABSENT 0
List of 7 genes differentially expressed by 'LYMPHOVASCULAR_INVOLVEMENT'

Clinical variable #29: 'LYMPH_NODES_EXAMINED_HE_COUNT'

30 genes related to 'LYMPH_NODES_EXAMINED_HE_COUNT'.

Table S45.  Basic characteristics of clinical feature: 'LYMPH_NODES_EXAMINED_HE_COUNT'

LYMPH_NODES_EXAMINED_HE_COUNT Mean (SD) 1.04 (2.4)
  Significant markers N = 30
  pos. correlated 19
  neg. correlated 11
List of top 10 genes differentially expressed by 'LYMPH_NODES_EXAMINED_HE_COUNT'

Table S46.  Get Full Table List of top 10 genes significantly correlated to 'LYMPH_NODES_EXAMINED_HE_COUNT' by Spearman correlation test

SpearmanCorr corrP Q
KLRG2|346689 0.3296 2.492e-05 0.124
FLJ35390|255031 0.3219 3.499e-05 0.124
TMPRSS3|64699 -0.3192 4.115e-05 0.124
A2ML1|144568 0.3207 4.234e-05 0.124
APC2|10297 0.3192 4.358e-05 0.124
SERPINB12|89777 0.3899 4.668e-05 0.124
METTL8|79828 0.3154 5.133e-05 0.124
NOTCH1|4851 0.3119 6.274e-05 0.124
NCAM2|4685 0.3275 7.365e-05 0.124
PHC2|1912 -0.3089 7.447e-05 0.124
Clinical variable #30: 'LYMPH_NODES_EXAMINED'

No gene related to 'LYMPH_NODES_EXAMINED'.

Table S47.  Basic characteristics of clinical feature: 'LYMPH_NODES_EXAMINED'

LYMPH_NODES_EXAMINED Mean (SD) 22.35 (13)
  Significant markers N = 0
Clinical variable #31: 'KERATINIZATION_SQUAMOUS_CELL'

30 genes related to 'KERATINIZATION_SQUAMOUS_CELL'.

Table S48.  Basic characteristics of clinical feature: 'KERATINIZATION_SQUAMOUS_CELL'

KERATINIZATION_SQUAMOUS_CELL Labels N
  KERATINIZING SQUAMOUS CELL CARCINOMA 55
  NON-KERATINIZING SQUAMOUS CELL CARCINOMA 119
     
  Significant markers N = 30
  Higher in NON-KERATINIZING SQUAMOUS CELL CARCINOMA 30
  Higher in KERATINIZING SQUAMOUS CELL CARCINOMA 0
List of top 10 genes differentially expressed by 'KERATINIZATION_SQUAMOUS_CELL'

Table S49.  Get Full Table List of top 10 genes differentially expressed by 'KERATINIZATION_SQUAMOUS_CELL'

W(pos if higher in 'NON-KERATINIZING SQUAMOUS CELL CARCINOMA') wilcoxontestP Q AUC
QKI|9444 1788 1.56e-06 0.0284 0.7268
SYT17|51760 4616 1.38e-05 0.125 0.7053
MAP7D3|79649 1975 2.691e-05 0.139 0.6982
SPG7|6687 4561 3.059e-05 0.139 0.6969
C9ORF30|91283 2029 5.738e-05 0.166 0.69
SFXN2|118980 4512 6.062e-05 0.166 0.6894
FRAT2|23401 4508 6.403e-05 0.166 0.6888
BCL2L2|599 2088 0.0001269 0.194 0.681
JAZF1|221895 2090 0.0001303 0.194 0.6807
TMEM180|79847 4455 0.0001303 0.194 0.6807
Clinical variable #32: 'INITIAL_PATHOLOGIC_DX_YEAR'

30 genes related to 'INITIAL_PATHOLOGIC_DX_YEAR'.

Table S50.  Basic characteristics of clinical feature: 'INITIAL_PATHOLOGIC_DX_YEAR'

INITIAL_PATHOLOGIC_DX_YEAR Mean (SD) 2008.29 (4.8)
  Significant markers N = 30
  pos. correlated 10
  neg. correlated 20
List of top 10 genes differentially expressed by 'INITIAL_PATHOLOGIC_DX_YEAR'

Table S51.  Get Full Table List of top 10 genes significantly correlated to 'INITIAL_PATHOLOGIC_DX_YEAR' by Spearman correlation test

SpearmanCorr corrP Q
?|390284 -0.2917 2.943e-07 0.00535
RPPH1|85495 -0.2596 4.866e-06 0.037
SNAPC5|10302 -0.2565 6.338e-06 0.037
C19ORF33|64073 -0.2536 8.146e-06 0.037
POM121L8P|29797 0.3038 4.159e-05 0.111
RCL1|10171 -0.2332 4.272e-05 0.111
RPL36A|6173 -0.2332 4.273e-05 0.111
LIMD1|8994 0.2302 5.392e-05 0.113
C9ORF171|389799 0.3228 5.602e-05 0.113
RPL13AP6|644511 -0.2235 8.958e-05 0.15
Clinical variable #33: 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

No gene related to 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'.

Table S52.  Basic characteristics of clinical feature: 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

HISTORY_HORMONAL_CONTRACEPTIVES_USE Labels N
  CURRENT USER 15
  FORMER USER 53
  NEVER USED 89
     
  Significant markers N = 0
Clinical variable #34: 'HEIGHT_CM_AT_DIAGNOSIS'

30 genes related to 'HEIGHT_CM_AT_DIAGNOSIS'.

Table S53.  Basic characteristics of clinical feature: 'HEIGHT_CM_AT_DIAGNOSIS'

HEIGHT_CM_AT_DIAGNOSIS Mean (SD) 161.01 (7.1)
  Significant markers N = 30
  pos. correlated 20
  neg. correlated 10
List of top 10 genes differentially expressed by 'HEIGHT_CM_AT_DIAGNOSIS'

Table S54.  Get Full Table List of top 10 genes significantly correlated to 'HEIGHT_CM_AT_DIAGNOSIS' by Spearman correlation test

SpearmanCorr corrP Q
RRAD|6236 0.2705 9.32e-06 0.0658
C19ORF33|64073 0.2693 1.024e-05 0.0658
ZNF107|51427 -0.265 1.437e-05 0.0658
?|390284 0.2659 1.448e-05 0.0658
FOSB|2354 0.2575 2.545e-05 0.0752
LOC541471|541471 0.256 2.84e-05 0.0752
ANP32C|23520 0.2582 3.113e-05 0.0752
DUSP1|1843 0.254 3.306e-05 0.0752
SPAG7|9552 0.2501 4.372e-05 0.0884
PLK3|1263 0.2468 5.555e-05 0.101
Clinical variable #35: 'CORPUS_INVOLVEMENT'

No gene related to 'CORPUS_INVOLVEMENT'.

Table S55.  Basic characteristics of clinical feature: 'CORPUS_INVOLVEMENT'

CORPUS_INVOLVEMENT Labels N
  ABSENT 99
  PRESENT 19
     
  Significant markers N = 0
Clinical variable #36: 'CHEMO_CONCURRENT_TYPE'

No gene related to 'CHEMO_CONCURRENT_TYPE'.

Table S56.  Basic characteristics of clinical feature: 'CHEMO_CONCURRENT_TYPE'

CHEMO_CONCURRENT_TYPE Labels N
  CARBOPLATIN 7
  CISPLATIN 102
  OTHER 2
     
  Significant markers N = 0
Clinical variable #37: 'CERVIX_SUV_RESULTS'

One gene related to 'CERVIX_SUV_RESULTS'.

Table S57.  Basic characteristics of clinical feature: 'CERVIX_SUV_RESULTS'

CERVIX_SUV_RESULTS Mean (SD) 13.22 (7.2)
  Significant markers N = 1
  pos. correlated 1
  neg. correlated 0
List of one gene differentially expressed by 'CERVIX_SUV_RESULTS'

Table S58.  Get Full Table List of one gene significantly correlated to 'CERVIX_SUV_RESULTS' by Spearman correlation test

SpearmanCorr corrP Q
HDHD1A|8226 0.848 0 0
Clinical variable #38: 'AGE_AT_DIAGNOSIS'

30 genes related to 'AGE_AT_DIAGNOSIS'.

Table S59.  Basic characteristics of clinical feature: 'AGE_AT_DIAGNOSIS'

AGE_AT_DIAGNOSIS Mean (SD) 48.24 (14)
  Significant markers N = 30
  pos. correlated 15
  neg. correlated 15
List of top 10 genes differentially expressed by 'AGE_AT_DIAGNOSIS'

Table S60.  Get Full Table List of top 10 genes significantly correlated to 'AGE_AT_DIAGNOSIS' by Spearman correlation test

SpearmanCorr corrP Q
NXNL2|158046 -0.3808 4.636e-11 8.43e-07
PGR|5241 -0.3177 1.569e-08 0.00012
RHOF|54509 -0.3075 4.421e-08 0.00012
CORO6|84940 -0.3074 4.461e-08 0.00012
GPR97|222487 -0.3074 4.496e-08 0.00012
IL24|11009 -0.3106 4.61e-08 0.00012
LANCL1|10314 0.3071 4.634e-08 0.00012
CSF3|1440 -0.3101 5.367e-08 0.000122
DIO2|1734 -0.3032 6.946e-08 0.00014
RRAGD|58528 0.2975 1.25e-07 0.000227
Clinical variable #39: 'CLINICAL_STAGE'

30 genes related to 'CLINICAL_STAGE'.

Table S61.  Basic characteristics of clinical feature: 'CLINICAL_STAGE'

CLINICAL_STAGE Labels N
  STAGE I 5
  STAGE IA 1
  STAGE IA1 1
  STAGE IA2 1
  STAGE IB 38
  STAGE IB1 77
  STAGE IB2 39
  STAGE II 5
  STAGE IIA 9
  STAGE IIA1 5
  STAGE IIA2 7
  STAGE IIB 43
  STAGE III 1
  STAGE IIIA 2
  STAGE IIIB 42
  STAGE IVA 9
  STAGE IVB 12
     
  Significant markers N = 30
List of top 10 genes differentially expressed by 'CLINICAL_STAGE'

Table S62.  Get Full Table List of top 10 genes differentially expressed by 'CLINICAL_STAGE'

kruskal_wallis_P Q
TRIM25|7706 4.555e-09 8.28e-05
FBXL18|80028 1.058e-07 9e-04
RGS1|5996 1.875e-07 9e-04
ZC3HAV1|56829 1.979e-07 9e-04
PPFIA4|8497 6.372e-07 0.00232
CYB561D1|284613 1.342e-05 0.0407
ZBTB3|79842 1.719e-05 0.0447
TSC22D3|1831 2.85e-05 0.0648
DNAJC5|80331 3.861e-05 0.0771
APLN|8862 4.241e-05 0.0771
Methods & Data
Input

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

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

  • Number of patients = 304

  • Number of genes = 18187

  • Number of clinical features = 39

Selected clinical features

  • Further details on clinical features selected for this analysis, please find a documentation on selected CDEs (Clinical Data Elements). The first column of the file is a formula to convert values and the second column is a clinical parameter name.

  • Survival time data

    • Survival time data is a combined value of days_to_death and days_to_last_followup. For each patient, it creates a combined value 'days_to_death_or_last_fup' using conversion process below.

      • if 'vital_status'==1(dead), 'days_to_last_followup' is always NA. Thus, uses 'days_to_death' value for 'days_to_death_or_fup'

      • if 'vital_status'==0(alive),

        • if 'days_to_death'==NA & 'days_to_last_followup'!=NA, uses 'days_to_last_followup' value for 'days_to_death_or_fup'

        • if 'days_to_death'!=NA, excludes this case in survival analysis and report the case.

      • if 'vital_status'==NA,excludes this case in survival analysis and report the case.

    • cf. In certain diesase types such as SKCM, days_to_death parameter is replaced with time_from_specimen_dx or time_from_specimen_procurement_to_death .

  • This analysis excluded clinical variables that has only NA values.

Survival analysis

For survival clinical features, logrank test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values comparing quantile intervals using the 'coxph' function in R. Kaplan-Meier survival curves were plotted using quantile intervals at c(0, 0.25, 0.50, 0.75, 1). If there is only one interval group, it will not try survival analysis.

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

Wilcoxon rank sum test (Mann-Whitney U test)

For two groups (mutant or wild-type) of continuous type of clinical data, wilcoxon rank sum test (Mann and Whitney, 1947) was applied to compare their mean difference using 'wilcox.test(continuous.clinical ~ as.factor(group), exact=FALSE)' function in R. This test is equivalent to the Mann-Whitney test.

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] Mann and Whitney, On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other, Annals of Mathematical Statistics 18 (1), 50-60 (1947)
[4] 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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