Correlation between miRseq expression and clinical features
Overview
Introduction

This pipeline uses various statistical tests to identify miRs whose log2 expression levels correlated to selected clinical features. The input file " CESC-TP.miRseq_RPKM_log2.txt " is generated in the pipeline miRseq_Preprocess in the stddata run.

Summary

Testing the association between 543 miRs and 39 clinical features across 307 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 20 clinical features related to at least one miRs.

  • 17 miRs correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

    • HSA-MIR-532 ,  HSA-MIR-502 ,  HSA-MIR-101-1 ,  HSA-MIR-378C ,  HSA-MIR-150 ,  ...

  • 30 miRs correlated to 'YEARS_TO_BIRTH'.

    • HSA-MIR-424 ,  HSA-MIR-455 ,  HSA-MIR-1468 ,  HSA-MIR-450A-2 ,  HSA-MIR-31 ,  ...

  • 30 miRs correlated to 'PATHOLOGY_T_STAGE'.

    • HSA-MIR-144 ,  HSA-MIR-424 ,  HSA-MIR-486 ,  HSA-MIR-451 ,  HSA-MIR-185 ,  ...

  • 12 miRs correlated to 'RADIATION_THERAPY'.

    • HSA-MIR-3917 ,  HSA-MIR-374A ,  HSA-MIR-185 ,  HSA-MIR-500A ,  HSA-MIR-7-1 ,  ...

  • 30 miRs correlated to 'HISTOLOGICAL_TYPE'.

    • HSA-MIR-205 ,  HSA-MIR-944 ,  HSA-MIR-375 ,  HSA-MIR-194-2 ,  HSA-MIR-10A ,  ...

  • 5 miRs correlated to 'RACE'.

    • HSA-MIR-24-2 ,  HSA-MIR-3130-1 ,  HSA-MIR-2355 ,  HSA-MIR-454 ,  HSA-MIR-185

  • 30 miRs correlated to 'WEIGHT_KG_AT_DIAGNOSIS'.

    • HSA-MIR-592 ,  HSA-MIR-548B ,  HSA-MIR-3130-1 ,  HSA-MIR-3690 ,  HSA-MIR-223 ,  ...

  • 15 miRs correlated to 'TUMOR_STATUS'.

    • HSA-MIR-150 ,  HSA-MIR-378C ,  HSA-MIR-155 ,  HSA-MIR-361 ,  HSA-MIR-451 ,  ...

  • 30 miRs correlated to 'NEOPLASM_HISTOLOGIC_GRADE'.

    • HSA-MIR-486 ,  HSA-MIR-421 ,  HSA-MIR-185 ,  HSA-MIR-144 ,  HSA-MIR-23B ,  ...

  • 15 miRs correlated to 'TOBACCO_SMOKING_HISTORY'.

    • HSA-MIR-33A ,  HSA-MIR-4326 ,  HSA-MIR-27B ,  HSA-MIR-146B ,  HSA-MIR-1274B ,  ...

  • 30 miRs correlated to 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'.

    • HSA-MIR-185 ,  HSA-MIR-340 ,  HSA-MIR-758 ,  HSA-MIR-216A ,  HSA-MIR-146B ,  ...

  • 3 miRs correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

    • HSA-MIR-1287 ,  HSA-MIR-19A ,  HSA-MIR-212

  • 1 miR correlated to 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'.

    • HSA-MIR-26B

  • 20 miRs correlated to 'MENOPAUSE_STATUS'.

    • HSA-MIR-424 ,  HSA-MIR-1468 ,  HSA-MIR-503 ,  HSA-MIR-125B-2 ,  HSA-MIR-1274B ,  ...

  • 22 miRs correlated to 'KERATINIZATION_SQUAMOUS_CELL'.

    • HSA-MIR-152 ,  HSA-MIR-27A ,  HSA-MIR-23C ,  HSA-MIR-191 ,  HSA-MIR-23A ,  ...

  • 30 miRs correlated to 'INITIAL_PATHOLOGIC_DX_YEAR'.

    • HSA-MIR-1274B ,  HSA-MIR-19A ,  HSA-MIR-212 ,  HSA-MIR-660 ,  HSA-MIR-326 ,  ...

  • 2 miRs correlated to 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'.

    • HSA-MIR-338 ,  HSA-MIR-26B

  • 13 miRs correlated to 'HEIGHT_CM_AT_DIAGNOSIS'.

    • HSA-MIR-320B-2 ,  HSA-MIR-320E ,  HSA-MIR-320D-1 ,  HSA-MIR-3130-1 ,  HSA-MIR-548Q ,  ...

  • 30 miRs correlated to 'AGE_AT_DIAGNOSIS'.

    • HSA-MIR-424 ,  HSA-MIR-455 ,  HSA-MIR-1468 ,  HSA-MIR-450A-2 ,  HSA-MIR-503 ,  ...

  • 12 miRs correlated to 'CLINICAL_STAGE'.

    • HSA-MIR-144 ,  HSA-MIR-451 ,  HSA-MIR-486 ,  HSA-MIR-218-2 ,  HSA-MIR-185 ,  ...

  • No miRs correlated to 'PATHOLOGY_N_STAGE', 'PATHOLOGY_M_STAGE', 'NUMBER_PACK_YEARS_SMOKED', 'NUMBER_OF_LYMPH_NODES', 'ETHNICITY', 'TOBACCO_SMOKING_YEAR_STOPPED', 'TOBACCO_SMOKING_PACK_YEARS_SMOKED', 'AGEBEGANSMOKINGINYEARS', 'RADIATION_THERAPY_STATUS', 'PREGNANCIES_COUNT_TOTAL', 'PREGNANCIES_COUNT_STILLBIRTH', 'PREGNANCIES_COUNT_ECTOPIC', 'POS_LYMPH_NODE_LOCATION', 'LYMPHOVASCULAR_INVOLVEMENT', 'LYMPH_NODES_EXAMINED_HE_COUNT', 'LYMPH_NODES_EXAMINED', 'CORPUS_INVOLVEMENT', 'CHEMO_CONCURRENT_TYPE', and 'CERVIX_SUV_RESULTS'.

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 miRs that are significantly associated with each clinical feature at P value < 0.05 and Q value < 0.3.

Clinical feature Statistical test Significant miRs Associated with                 Associated with
DAYS_TO_DEATH_OR_LAST_FUP Cox regression test N=17   N=NA   N=NA
YEARS_TO_BIRTH Spearman correlation test N=30 older N=14 younger N=16
PATHOLOGY_T_STAGE Spearman correlation test N=30 higher stage N=10 lower stage N=20
PATHOLOGY_N_STAGE Wilcoxon test   N=0        
PATHOLOGY_M_STAGE Wilcoxon test   N=0        
RADIATION_THERAPY Wilcoxon test N=12 yes N=12 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=0        
RACE Kruskal-Wallis test N=5        
ETHNICITY Wilcoxon test   N=0        
WEIGHT_KG_AT_DIAGNOSIS Spearman correlation test N=30 higher weight_kg_at_diagnosis N=24 lower weight_kg_at_diagnosis N=6
TUMOR_STATUS Wilcoxon test N=15 with tumor N=15 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=15 higher tobacco_smoking_history N=10 lower tobacco_smoking_history N=5
AGEBEGANSMOKINGINYEARS Spearman correlation test   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=30 higher pregnancy_spontaneous_abortion_count N=12 lower pregnancy_spontaneous_abortion_count N=18
PREGNANCIES_COUNT_LIVE_BIRTH Spearman correlation test N=3 higher pregnancies_count_live_birth N=1 lower pregnancies_count_live_birth N=2
PREGNANCY_THERAPEUTIC_ABORTION_COUNT Spearman correlation test N=1 higher pregnancy_therapeutic_abortion_count N=0 lower pregnancy_therapeutic_abortion_count N=1
PREGNANCIES_COUNT_ECTOPIC Spearman correlation test   N=0        
POS_LYMPH_NODE_LOCATION Kruskal-Wallis test   N=0        
MENOPAUSE_STATUS Kruskal-Wallis test N=20        
LYMPHOVASCULAR_INVOLVEMENT Wilcoxon test   N=0        
LYMPH_NODES_EXAMINED_HE_COUNT Spearman correlation test   N=0        
LYMPH_NODES_EXAMINED Spearman correlation test   N=0        
KERATINIZATION_SQUAMOUS_CELL Wilcoxon test N=22 non-keratinizing squamous cell carcinoma N=22 keratinizing squamous cell carcinoma N=0
INITIAL_PATHOLOGIC_DX_YEAR Spearman correlation test N=30 higher initial_pathologic_dx_year N=8 lower initial_pathologic_dx_year N=22
HISTORY_HORMONAL_CONTRACEPTIVES_USE Kruskal-Wallis test N=2        
HEIGHT_CM_AT_DIAGNOSIS Spearman correlation test N=13 higher height_cm_at_diagnosis N=13 lower height_cm_at_diagnosis N=0
CORPUS_INVOLVEMENT Wilcoxon test   N=0        
CHEMO_CONCURRENT_TYPE Kruskal-Wallis test   N=0        
CERVIX_SUV_RESULTS Spearman correlation test   N=0        
AGE_AT_DIAGNOSIS Spearman correlation test N=30 higher age_at_diagnosis N=13 lower age_at_diagnosis N=17
CLINICAL_STAGE Kruskal-Wallis test N=12        
Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

17 miRs 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)
  censored N = 234
  death N = 72
     
  Significant markers N = 17
  associated with shorter survival NA
  associated with longer survival NA
List of top 10 miRs differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2.  Get Full Table List of top 10 miRs 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
HSA-MIR-532 0.000162 0.088 0.361
HSA-MIR-502 0.000376 0.1 0.331
HSA-MIR-101-1 0.000957 0.15 0.356
HSA-MIR-378C 0.00111 0.15 0.336
HSA-MIR-150 0.00168 0.18 0.341
HSA-MIR-541 0.00234 0.21 0.653
HSA-MIR-876 0.00324 0.24 0.576
HSA-MIR-1288 0.00393 0.24 0.421
HSA-MIR-361 0.00437 0.24 0.374
HSA-MIR-412 0.00441 0.24 0.55
Clinical variable #2: 'YEARS_TO_BIRTH'

30 miRs related to 'YEARS_TO_BIRTH'.

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

YEARS_TO_BIRTH Mean (SD) 48.2 (14)
  Significant markers N = 30
  pos. correlated 14
  neg. correlated 16
List of top 10 miRs differentially expressed by 'YEARS_TO_BIRTH'

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

SpearmanCorr corrP Q
HSA-MIR-424 -0.309 3.595e-08 1.95e-05
HSA-MIR-455 -0.2889 2.839e-07 7.71e-05
HSA-MIR-1468 0.2738 1.408e-06 0.000255
HSA-MIR-450A-2 -0.2293 5.302e-05 0.00695
HSA-MIR-31 -0.2258 6.911e-05 0.00695
HSA-MIR-503 -0.2244 7.675e-05 0.00695
HSA-MIR-204 0.2301 0.0001023 0.00793
HSA-MIR-653 0.2054 0.0003501 0.0238
HSA-MIR-133A-2 0.2706 0.0006093 0.0351
HSA-MIR-125B-2 0.1943 0.0006458 0.0351
Clinical variable #3: 'PATHOLOGY_T_STAGE'

30 miRs 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 141
  T2 72
  T3 21
  T4 10
     
  Significant markers N = 30
  pos. correlated 10
  neg. correlated 20
List of top 10 miRs differentially expressed by 'PATHOLOGY_T_STAGE'

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

SpearmanCorr corrP Q
HSA-MIR-144 0.3186 3.684e-07 2e-04
HSA-MIR-424 -0.3037 1.339e-06 0.000275
HSA-MIR-486 0.3022 1.52e-06 0.000275
HSA-MIR-451 0.2985 2.066e-06 0.00028
HSA-MIR-185 0.2832 6.989e-06 0.000759
HSA-MIR-450A-2 -0.2644 2.872e-05 0.0026
HSA-MIR-1247 -0.2491 8.662e-05 0.00672
HSA-MIR-181A-1 0.2426 0.0001291 0.00876
HSA-MIR-10A -0.2382 0.000173 0.0104
HSA-MIR-103-1 0.2353 0.0002087 0.0105
Clinical variable #4: 'PATHOLOGY_N_STAGE'

No miR related to 'PATHOLOGY_N_STAGE'.

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

PATHOLOGY_N_STAGE Labels N
  N0 135
  N1 60
     
  Significant markers N = 0
Clinical variable #5: 'PATHOLOGY_M_STAGE'

No miR 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 = 0
Clinical variable #6: 'RADIATION_THERAPY'

12 miRs related to 'RADIATION_THERAPY'.

Table S9.  Basic characteristics of clinical feature: 'RADIATION_THERAPY'

RADIATION_THERAPY Labels N
  NO 55
  YES 129
     
  Significant markers N = 12
  Higher in YES 12
  Higher in NO 0
List of top 10 miRs differentially expressed by 'RADIATION_THERAPY'

Table S10.  Get Full Table List of top 10 miRs differentially expressed by 'RADIATION_THERAPY'

W(pos if higher in 'YES') wilcoxontestP Q AUC
HSA-MIR-3917 2137 3.301e-05 0.0179 0.6941
HSA-MIR-374A 2365 0.0003517 0.0955 0.6667
HSA-MIR-185 4659 0.0007815 0.132 0.6567
HSA-MIR-500A 2472 0.001152 0.132 0.6516
HSA-MIR-7-1 2477 0.001215 0.132 0.6509
HSA-MIR-181A-1 4601 0.001453 0.132 0.6485
HSA-MIR-107 4498 0.004073 0.279 0.634
HSA-MIR-320A 2598 0.004112 0.279 0.6338
HSA-MIR-486 4472 0.005209 0.296 0.6303
HSA-MIR-28 2630 0.00556 0.296 0.6293
Clinical variable #7: 'HISTOLOGICAL_TYPE'

30 miRs related to 'HISTOLOGICAL_TYPE'.

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

HISTOLOGICAL_TYPE Labels N
  ADENOSQUAMOUS 6
  CERVICAL SQUAMOUS CELL CARCINOMA 254
  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 miRs differentially expressed by 'HISTOLOGICAL_TYPE'

Table S12.  Get Full Table List of top 10 miRs differentially expressed by 'HISTOLOGICAL_TYPE'

kruskal_wallis_P Q
HSA-MIR-205 4.976e-22 2.7e-19
HSA-MIR-944 5.309e-19 1.44e-16
HSA-MIR-375 5.394e-18 9.76e-16
HSA-MIR-194-2 1.364e-14 1.85e-12
HSA-MIR-10A 5.094e-14 5.53e-12
HSA-MIR-192 1.415e-13 1.28e-11
HSA-MIR-194-1 1.771e-13 1.37e-11
HSA-MIR-203 4.71e-13 3.2e-11
HSA-MIR-1293 8.087e-13 4.88e-11
HSA-MIR-221 6.133e-12 3.33e-10
Clinical variable #8: 'NUMBER_PACK_YEARS_SMOKED'

No miR related to 'NUMBER_PACK_YEARS_SMOKED'.

Table S13.  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'

No miR related to 'NUMBER_OF_LYMPH_NODES'.

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

NUMBER_OF_LYMPH_NODES Mean (SD) 1.04 (2.4)
  Significant markers N = 0
Clinical variable #10: 'RACE'

5 miRs related to 'RACE'.

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

RACE Labels N
  AMERICAN INDIAN OR ALASKA NATIVE 8
  ASIAN 20
  BLACK OR AFRICAN AMERICAN 30
  NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 2
  WHITE 211
     
  Significant markers N = 5
List of 5 miRs differentially expressed by 'RACE'

Table S16.  Get Full Table List of 5 miRs differentially expressed by 'RACE'

kruskal_wallis_P Q
HSA-MIR-24-2 0.0004318 0.211
HSA-MIR-3130-1 0.001064 0.211
HSA-MIR-2355 0.001539 0.211
HSA-MIR-454 0.001875 0.211
HSA-MIR-185 0.001941 0.211
Clinical variable #11: 'ETHNICITY'

No miR related to 'ETHNICITY'.

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

ETHNICITY Labels N
  HISPANIC OR LATINO 24
  NOT HISPANIC OR LATINO 171
     
  Significant markers N = 0
Clinical variable #12: 'WEIGHT_KG_AT_DIAGNOSIS'

30 miRs related to 'WEIGHT_KG_AT_DIAGNOSIS'.

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

WEIGHT_KG_AT_DIAGNOSIS Mean (SD) 73.04 (22)
  Significant markers N = 30
  pos. correlated 24
  neg. correlated 6
List of top 10 miRs differentially expressed by 'WEIGHT_KG_AT_DIAGNOSIS'

Table S19.  Get Full Table List of top 10 miRs significantly correlated to 'WEIGHT_KG_AT_DIAGNOSIS' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-592 0.2392 6.163e-05 0.0335
HSA-MIR-548B 0.214 0.0006741 0.169
HSA-MIR-3130-1 0.1938 0.001265 0.169
HSA-MIR-3690 0.2066 0.002015 0.169
HSA-MIR-223 -0.1837 0.002105 0.169
HSA-MIR-639 0.205 0.002412 0.169
HSA-MIR-518C 0.2761 0.002478 0.169
HSA-MIR-618 -0.2062 0.002488 0.169
HSA-MIR-181C 0.1749 0.003447 0.179
HSA-MIR-24-1 0.1747 0.003472 0.179
Clinical variable #13: 'TUMOR_STATUS'

15 miRs related to 'TUMOR_STATUS'.

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

TUMOR_STATUS Labels N
  TUMOR FREE 201
  WITH TUMOR 80
     
  Significant markers N = 15
  Higher in WITH TUMOR 15
  Higher in TUMOR FREE 0
List of top 10 miRs differentially expressed by 'TUMOR_STATUS'

Table S21.  Get Full Table List of top 10 miRs differentially expressed by 'TUMOR_STATUS'

W(pos if higher in 'WITH TUMOR') wilcoxontestP Q AUC
HSA-MIR-150 5892 0.0004768 0.0902 0.6336
HSA-MIR-378C 5882 0.0005414 0.0902 0.6324
HSA-MIR-155 5951 0.0006801 0.0902 0.6299
HSA-MIR-361 5965 0.0007389 0.0902 0.629
HSA-MIR-451 10063 0.001001 0.0902 0.6258
HSA-MIR-144 10052 0.001067 0.0902 0.6251
HSA-MIR-142 6043 0.001163 0.0902 0.6242
HSA-MIR-556 6652 0.001996 0.135 0.6323
HSA-MIR-301B 8985 0.002469 0.149 0.6195
HSA-MIR-486 9850 0.003244 0.176 0.6126
Clinical variable #14: 'NEOPLASM_HISTOLOGIC_GRADE'

30 miRs related to 'NEOPLASM_HISTOLOGIC_GRADE'.

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

NEOPLASM_HISTOLOGIC_GRADE Labels N
  G1 18
  G2 136
  G3 120
  G4 1
  GX 24
     
  Significant markers N = 30
List of top 10 miRs differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

Table S23.  Get Full Table List of top 10 miRs differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

kruskal_wallis_P Q
HSA-MIR-486 0.0002665 0.0552
HSA-MIR-421 0.0002798 0.0552
HSA-MIR-185 0.0003936 0.0552
HSA-MIR-144 0.0004068 0.0552
HSA-MIR-23B 0.0006318 0.0686
HSA-MIR-19A 0.000839 0.0759
HSA-MIR-496 0.001091 0.0847
HSA-MIR-346 0.001686 0.0913
HSA-MIR-17 0.001834 0.0913
HSA-MIR-216B 0.001901 0.0913
Clinical variable #15: 'TOBACCO_SMOKING_YEAR_STOPPED'

No miR related to 'TOBACCO_SMOKING_YEAR_STOPPED'.

Table S24.  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 miR related to 'TOBACCO_SMOKING_PACK_YEARS_SMOKED'.

Table S25.  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'

15 miRs related to 'TOBACCO_SMOKING_HISTORY'.

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

TOBACCO_SMOKING_HISTORY Mean (SD) 1.83 (1.1)
  Value N
  1 146
  2 64
  3 9
  4 40
  5 4
     
  Significant markers N = 15
  pos. correlated 10
  neg. correlated 5
List of top 10 miRs differentially expressed by 'TOBACCO_SMOKING_HISTORY'

Table S27.  Get Full Table List of top 10 miRs significantly correlated to 'TOBACCO_SMOKING_HISTORY' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-33A 0.258 2.267e-05 0.0123
HSA-MIR-4326 -0.2464 0.0001268 0.0344
HSA-MIR-27B 0.2184 0.0003584 0.0649
HSA-MIR-146B -0.2103 0.0005973 0.0659
HSA-MIR-1274B 0.2108 0.0006071 0.0659
HSA-MIR-26A-2 0.1943 0.001548 0.12
HSA-MIR-27A 0.1935 0.001615 0.12
HSA-MIR-501 -0.1919 0.001768 0.12
HSA-MIR-1537 -0.2243 0.002762 0.167
HSA-MIR-3609 -0.2633 0.003966 0.215
Clinical variable #18: 'AGEBEGANSMOKINGINYEARS'

No miR related to 'AGEBEGANSMOKINGINYEARS'.

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

AGEBEGANSMOKINGINYEARS Mean (SD) 21.14 (7.7)
  Significant markers N = 0
Clinical variable #19: 'RADIATION_THERAPY_STATUS'

No miR related to 'RADIATION_THERAPY_STATUS'.

Table S29.  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 miR related to 'PREGNANCIES_COUNT_TOTAL'.

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

PREGNANCIES_COUNT_TOTAL Mean (SD) 3.61 (2.6)
  Significant markers N = 0
Clinical variable #21: 'PREGNANCIES_COUNT_STILLBIRTH'

No miR related to 'PREGNANCIES_COUNT_STILLBIRTH'.

Table S31.  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'

30 miRs related to 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'.

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

PREGNANCY_SPONTANEOUS_ABORTION_COUNT Mean (SD) 0.54 (0.95)
  Significant markers N = 30
  pos. correlated 12
  neg. correlated 18
List of top 10 miRs differentially expressed by 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'

Table S33.  Get Full Table List of top 10 miRs significantly correlated to 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-185 0.3532 1.146e-05 0.00622
HSA-MIR-340 0.2844 0.000482 0.0663
HSA-MIR-758 -0.2834 0.0005043 0.0663
HSA-MIR-216A -0.3877 0.0005891 0.0663
HSA-MIR-146B 0.2794 0.0006106 0.0663
HSA-MIR-19A 0.2663 0.001114 0.0746
HSA-MIR-539 -0.2671 0.001163 0.0746
HSA-MIR-379 -0.2593 0.001514 0.0746
HSA-MIR-3912 0.2628 0.001778 0.0746
HSA-MIR-15A 0.2549 0.001835 0.0746
Clinical variable #23: 'PREGNANCIES_COUNT_LIVE_BIRTH'

3 miRs related to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

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

PREGNANCIES_COUNT_LIVE_BIRTH Mean (SD) 2.84 (2)
  Significant markers N = 3
  pos. correlated 1
  neg. correlated 2
List of 3 miRs differentially expressed by 'PREGNANCIES_COUNT_LIVE_BIRTH'

Table S35.  Get Full Table List of 3 miRs significantly correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-1287 -0.2378 0.0001016 0.0551
HSA-MIR-19A 0.198 0.001274 0.28
HSA-MIR-212 -0.1946 0.001549 0.28
Clinical variable #24: 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'

One miR related to 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'.

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

PREGNANCY_THERAPEUTIC_ABORTION_COUNT Mean (SD) 0.85 (1.8)
  Significant markers N = 1
  pos. correlated 0
  neg. correlated 1
List of one miR differentially expressed by 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'

Table S37.  Get Full Table List of one miR significantly correlated to 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-26B -0.3242 0.0002692 0.146
Clinical variable #25: 'PREGNANCIES_COUNT_ECTOPIC'

No miR related to 'PREGNANCIES_COUNT_ECTOPIC'.

Table S38.  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 miR related to 'POS_LYMPH_NODE_LOCATION'.

Table S39.  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'

20 miRs related to 'MENOPAUSE_STATUS'.

Table S40.  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) 84
  PRE (<6 MONTHS SINCE LMP AND NO PRIOR BILATERAL OVARIECTOMY AND NOT ON ESTROGEN REPLACEMENT) 125
     
  Significant markers N = 20
List of top 10 miRs differentially expressed by 'MENOPAUSE_STATUS'

Table S41.  Get Full Table List of top 10 miRs differentially expressed by 'MENOPAUSE_STATUS'

kruskal_wallis_P Q
HSA-MIR-424 6.108e-05 0.0332
HSA-MIR-1468 0.0001562 0.0356
HSA-MIR-503 0.0001968 0.0356
HSA-MIR-125B-2 0.0002751 0.0373
HSA-MIR-1274B 0.0004469 0.0485
HSA-MIR-99A 0.0007493 0.0678
HSA-LET-7C 0.0008864 0.0688
HSA-MIR-455 0.001289 0.0875
HSA-MIR-3199-1 0.004019 0.221
HSA-MIR-4326 0.004448 0.221
Clinical variable #28: 'LYMPHOVASCULAR_INVOLVEMENT'

No miR related to 'LYMPHOVASCULAR_INVOLVEMENT'.

Table S42.  Basic characteristics of clinical feature: 'LYMPHOVASCULAR_INVOLVEMENT'

LYMPHOVASCULAR_INVOLVEMENT Labels N
  ABSENT 72
  PRESENT 80
     
  Significant markers N = 0
Clinical variable #29: 'LYMPH_NODES_EXAMINED_HE_COUNT'

No miR related to 'LYMPH_NODES_EXAMINED_HE_COUNT'.

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

LYMPH_NODES_EXAMINED_HE_COUNT Mean (SD) 1.04 (2.4)
  Significant markers N = 0
Clinical variable #30: 'LYMPH_NODES_EXAMINED'

No miR related to 'LYMPH_NODES_EXAMINED'.

Table S44.  Basic characteristics of clinical feature: 'LYMPH_NODES_EXAMINED'

LYMPH_NODES_EXAMINED Mean (SD) 22.28 (13)
  Significant markers N = 0
Clinical variable #31: 'KERATINIZATION_SQUAMOUS_CELL'

22 miRs related to 'KERATINIZATION_SQUAMOUS_CELL'.

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

KERATINIZATION_SQUAMOUS_CELL Labels N
  KERATINIZING SQUAMOUS CELL CARCINOMA 55
  NON-KERATINIZING SQUAMOUS CELL CARCINOMA 120
     
  Significant markers N = 22
  Higher in NON-KERATINIZING SQUAMOUS CELL CARCINOMA 22
  Higher in KERATINIZING SQUAMOUS CELL CARCINOMA 0
List of top 10 miRs differentially expressed by 'KERATINIZATION_SQUAMOUS_CELL'

Table S46.  Get Full Table List of top 10 miRs differentially expressed by 'KERATINIZATION_SQUAMOUS_CELL'

W(pos if higher in 'NON-KERATINIZING SQUAMOUS CELL CARCINOMA') wilcoxontestP Q AUC
HSA-MIR-152 2035 4.819e-05 0.0262 0.6917
HSA-MIR-27A 2128 0.0001663 0.0452 0.6776
HSA-MIR-23C 1565 0.0005318 0.0963 0.6767
HSA-MIR-191 4311 0.001163 0.132 0.6532
HSA-MIR-23A 2304 0.001376 0.132 0.6509
HSA-MIR-944 2292 0.001514 0.132 0.6498
HSA-MIR-193A 2323 0.001698 0.132 0.648
HSA-MIR-30C-2 4241 0.002504 0.17 0.6426
HSA-MIR-24-2 2384 0.003255 0.196 0.6388
HSA-MIR-93 4192 0.004165 0.226 0.6352
Clinical variable #32: 'INITIAL_PATHOLOGIC_DX_YEAR'

30 miRs related to 'INITIAL_PATHOLOGIC_DX_YEAR'.

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

INITIAL_PATHOLOGIC_DX_YEAR Mean (SD) 2008.32 (4.8)
  Significant markers N = 30
  pos. correlated 8
  neg. correlated 22
List of top 10 miRs differentially expressed by 'INITIAL_PATHOLOGIC_DX_YEAR'

Table S48.  Get Full Table List of top 10 miRs significantly correlated to 'INITIAL_PATHOLOGIC_DX_YEAR' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-1274B -0.416 4.124e-14 2.24e-11
HSA-MIR-19A 0.3764 1.061e-11 2.49e-09
HSA-MIR-212 -0.3741 1.443e-11 2.49e-09
HSA-MIR-660 0.3723 1.836e-11 2.49e-09
HSA-MIR-326 -0.344 8.713e-10 9.46e-08
HSA-MIR-24-2 -0.3371 1.536e-09 1.39e-07
HSA-MIR-15A 0.3332 2.432e-09 1.89e-07
HSA-MIR-19B-2 0.3298 3.6e-09 2.44e-07
HSA-MIR-3130-1 -0.3295 4.989e-09 3.01e-07
HSA-MIR-143 -0.3232 7.638e-09 4.15e-07
Clinical variable #33: 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

2 miRs related to 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'.

Table S49.  Basic characteristics of clinical feature: 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

HISTORY_HORMONAL_CONTRACEPTIVES_USE Labels N
  CURRENT USER 15
  FORMER USER 54
  NEVER USED 90
     
  Significant markers N = 2
List of 2 miRs differentially expressed by 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

Table S50.  Get Full Table List of 2 miRs differentially expressed by 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

kruskal_wallis_P Q
HSA-MIR-338 0.0006624 0.226
HSA-MIR-26B 0.0008337 0.226
Clinical variable #34: 'HEIGHT_CM_AT_DIAGNOSIS'

13 miRs related to 'HEIGHT_CM_AT_DIAGNOSIS'.

Table S51.  Basic characteristics of clinical feature: 'HEIGHT_CM_AT_DIAGNOSIS'

HEIGHT_CM_AT_DIAGNOSIS Mean (SD) 160.95 (7.3)
  Significant markers N = 13
  pos. correlated 13
  neg. correlated 0
List of top 10 miRs differentially expressed by 'HEIGHT_CM_AT_DIAGNOSIS'

Table S52.  Get Full Table List of top 10 miRs significantly correlated to 'HEIGHT_CM_AT_DIAGNOSIS' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-320B-2 0.2564 2.483e-05 0.0135
HSA-MIR-320E 0.3409 0.0002348 0.0487
HSA-MIR-320D-1 0.2484 0.0002691 0.0487
HSA-MIR-3130-1 0.209 0.0006967 0.0836
HSA-MIR-548Q 0.2505 0.0007697 0.0836
HSA-MIR-1274B 0.2014 0.001047 0.0948
HSA-MIR-23C 0.214 0.001405 0.096
HSA-MIR-320C-1 0.2034 0.001435 0.096
HSA-MIR-1910 0.2279 0.001655 0.096
HSA-MIR-551A 0.2311 0.001908 0.096
Clinical variable #35: 'CORPUS_INVOLVEMENT'

No miR related to 'CORPUS_INVOLVEMENT'.

Table S53.  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 miR related to 'CHEMO_CONCURRENT_TYPE'.

Table S54.  Basic characteristics of clinical feature: 'CHEMO_CONCURRENT_TYPE'

CHEMO_CONCURRENT_TYPE Labels N
  CARBOPLATIN 7
  CISPLATIN 104
  OTHER 2
     
  Significant markers N = 0
Clinical variable #37: 'CERVIX_SUV_RESULTS'

No miR related to 'CERVIX_SUV_RESULTS'.

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

CERVIX_SUV_RESULTS Mean (SD) 13.22 (7.2)
  Significant markers N = 0
Clinical variable #38: 'AGE_AT_DIAGNOSIS'

30 miRs related to 'AGE_AT_DIAGNOSIS'.

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

AGE_AT_DIAGNOSIS Mean (SD) 48.27 (14)
  Significant markers N = 30
  pos. correlated 13
  neg. correlated 17
List of top 10 miRs differentially expressed by 'AGE_AT_DIAGNOSIS'

Table S57.  Get Full Table List of top 10 miRs significantly correlated to 'AGE_AT_DIAGNOSIS' by Spearman correlation test

SpearmanCorr corrP Q
HSA-MIR-424 -0.3117 2.41e-08 1.31e-05
HSA-MIR-455 -0.2826 4.797e-07 0.00013
HSA-MIR-1468 0.272 1.533e-06 0.000277
HSA-MIR-450A-2 -0.2298 4.809e-05 0.00576
HSA-MIR-503 -0.2285 5.307e-05 0.00576
HSA-MIR-204 0.2351 6.686e-05 0.00605
HSA-MIR-31 -0.2146 0.0001513 0.0117
HSA-MIR-653 0.2112 0.0002244 0.0152
HSA-MIR-133A-2 0.2706 0.0005853 0.0353
HSA-MIR-450A-1 -0.1912 0.000792 0.043
Clinical variable #39: 'CLINICAL_STAGE'

12 miRs related to 'CLINICAL_STAGE'.

Table S58.  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 78
  STAGE IB2 39
  STAGE II 5
  STAGE IIA 9
  STAGE IIA1 5
  STAGE IIA2 7
  STAGE IIB 44
  STAGE III 1
  STAGE IIIA 3
  STAGE IIIB 42
  STAGE IVA 9
  STAGE IVB 12
     
  Significant markers N = 12
List of top 10 miRs differentially expressed by 'CLINICAL_STAGE'

Table S59.  Get Full Table List of top 10 miRs differentially expressed by 'CLINICAL_STAGE'

kruskal_wallis_P Q
HSA-MIR-144 2.675e-05 0.0103
HSA-MIR-451 3.908e-05 0.0103
HSA-MIR-486 5.686e-05 0.0103
HSA-MIR-218-2 0.001166 0.109
HSA-MIR-185 0.001183 0.109
HSA-MIR-3610 0.001204 0.109
HSA-MIR-424 0.001617 0.125
HSA-MIR-140 0.003077 0.206
HSA-MIR-193A 0.003537 0.206
HSA-MIR-375 0.003792 0.206
Methods & Data
Input

  • Expresson data file = CESC-TP.miRseq_RPKM_log2.txt

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

  • Number of patients = 307

  • Number of miRs = 543

  • 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.

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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