Correlation between gene methylation status and clinical features

Overview

Introduction

This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features. The input file "CESC-TP.meth.by_min_clin_corr.data.txt" is generated in the pipeline Methylation_Preprocess in stddata run.

Summary

Testing the association between 16894 genes and 39 clinical features across 307 samples, statistically thresholded by P value < 0.05 and Q value < 0.3, 19 clinical features related to at least one genes.

6 genes correlated to 'DAYS_TO_DEATH_OR_LAST_FUP'.

BRD8 , C1ORF61 , FAM13A , FBLN5 , MED7 , ...

30 genes correlated to 'YEARS_TO_BIRTH'.

C21ORF34 , SP4 , GLDC , CHRNB1 , MDFI , ...

30 genes correlated to 'PATHOLOGY_T_STAGE'.

CLCA3P , NUP35 , PMCH , MPP7 , DKFZP586I1420 , ...

4 genes correlated to 'RADIATION_THERAPY'.

MGST2 , PDCL , PHF17 , HLA-DRB1

30 genes correlated to 'HISTOLOGICAL_TYPE'.

ATP10D , C10ORF108 , TMEM117 , GPR87 , RGS12 , ...

30 genes correlated to 'NUMBER_OF_LYMPH_NODES'.

RCAN1 , NUAK1 , BCL9 , C3ORF71 , RNF20 , ...

30 genes correlated to 'RACE'.

SNX16 , PDXDC1 , IFNGR2 , TLE1 , NDUFS5 , ...

30 genes correlated to 'TUMOR_STATUS'.

PATL2 , CCR5 , FAM35B2 , SIT1 , CHRM3 , ...

30 genes correlated to 'NEOPLASM_HISTOLOGIC_GRADE'.

GMNN , MTF2 , MRPS9 , BRIX1 , PPP1R7 , ...

4 genes correlated to 'TOBACCO_SMOKING_HISTORY'.

NKD2 , SCAP , QDPR , HPSE

30 genes correlated to 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'.

GPRIN1 , TAF3 , POLR2D , C8ORF77 , ZBTB25 , ...

30 genes correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH'.

POLE , ZNF488 , PALM3 , PGF , ZNF713 , ...

30 genes correlated to 'MENOPAUSE_STATUS'.

C21ORF34 , CMTM7 , SALL3 , FBXW11 , RARB , ...

30 genes correlated to 'LYMPHOVASCULAR_INVOLVEMENT'.

MKRN2 , ZNF197 , HYAL3 , TMEM87B , GAL3ST3 , ...

30 genes correlated to 'LYMPH_NODES_EXAMINED_HE_COUNT'.

RCAN1 , NUAK1 , BCL9 , C3ORF71 , RNF20 , ...

30 genes correlated to 'LYMPH_NODES_EXAMINED'.

LOC643837 , HDAC1 , NIPA1 , TTLL10 , CCDC134 , ...

30 genes correlated to 'INITIAL_PATHOLOGIC_DX_YEAR'.

KLHL9 , MMD , RHOT2 , DCDC1 , C9ORF44 , ...

30 genes correlated to 'AGE_AT_DIAGNOSIS'.

C21ORF34 , SP4 , GLDC , CHRNB1 , MDFI , ...

30 genes correlated to 'CLINICAL_STAGE'.

ARF4 , C3ORF48 , DPY30 , ZNF322B , TMEM50A , ...

No genes correlated to 'PATHOLOGY_N_STAGE', 'PATHOLOGY_M_STAGE', 'NUMBER_PACK_YEARS_SMOKED', 'ETHNICITY', 'WEIGHT_KG_AT_DIAGNOSIS', 'TOBACCO_SMOKING_YEAR_STOPPED', 'TOBACCO_SMOKING_PACK_YEARS_SMOKED', 'AGEBEGANSMOKINGINYEARS', 'RADIATION_THERAPY_STATUS', 'PREGNANCIES_COUNT_TOTAL', 'PREGNANCIES_COUNT_STILLBIRTH', 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT', 'PREGNANCIES_COUNT_ECTOPIC', 'POS_LYMPH_NODE_LOCATION', 'KERATINIZATION_SQUAMOUS_CELL', 'HISTORY_HORMONAL_CONTRACEPTIVES_USE', 'HEIGHT_CM_AT_DIAGNOSIS', '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 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=6		N=NA		N=NA
YEARS_TO_BIRTH	Spearman correlation test	N=30	older	N=12	younger	N=18
PATHOLOGY_T_STAGE	Spearman correlation test	N=30	higher stage	N=3	lower stage	N=27
PATHOLOGY_N_STAGE	Wilcoxon test	N=0
PATHOLOGY_M_STAGE	Wilcoxon test	N=0
RADIATION_THERAPY	Wilcoxon test	N=4	yes	N=4	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=24	lower number_of_lymph_nodes	N=6
RACE	Kruskal-Wallis test	N=30
ETHNICITY	Wilcoxon test	N=0
WEIGHT_KG_AT_DIAGNOSIS	Spearman correlation test	N=0
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=4	higher tobacco_smoking_history	N=3	lower tobacco_smoking_history	N=1
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=16	lower pregnancy_spontaneous_abortion_count	N=14
PREGNANCIES_COUNT_LIVE_BIRTH	Spearman correlation test	N=30	higher pregnancies_count_live_birth	N=10	lower pregnancies_count_live_birth	N=20
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=30	present	N=30	absent	N=0
LYMPH_NODES_EXAMINED_HE_COUNT	Spearman correlation test	N=30	higher lymph_nodes_examined_he_count	N=24	lower lymph_nodes_examined_he_count	N=6
LYMPH_NODES_EXAMINED	Spearman correlation test	N=30	higher lymph_nodes_examined	N=30	lower lymph_nodes_examined	N=0
KERATINIZATION_SQUAMOUS_CELL	Wilcoxon test	N=0
INITIAL_PATHOLOGIC_DX_YEAR	Spearman correlation test	N=30	higher initial_pathologic_dx_year	N=2	lower initial_pathologic_dx_year	N=28
HISTORY_HORMONAL_CONTRACEPTIVES_USE	Kruskal-Wallis test	N=0
HEIGHT_CM_AT_DIAGNOSIS	Spearman correlation test	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=11	lower age_at_diagnosis	N=19
CLINICAL_STAGE	Kruskal-Wallis test	N=30

Clinical variable #1: 'DAYS_TO_DEATH_OR_LAST_FUP'

6 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)
	censored	N = 234
	death	N = 72

	Significant markers	N = 6
	associated with shorter survival	NA
	associated with longer survival	NA

List of 6 genes differentially expressed by 'DAYS_TO_DEATH_OR_LAST_FUP'

Table S2. Get Full Table List of 6 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
BRD8	2.3e-05	0.27	0.607
C1ORF61	5.3e-05	0.27	0.451
FAM13A	7.93e-05	0.27	0.328
FBLN5	8.66e-05	0.27	0.655
MED7	8.96e-05	0.27	0.632
CABLES1	9.44e-05	0.27	0.584

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)	48.2 (14)
	Significant markers	N = 30
	pos. correlated	12
	neg. correlated	18

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
C21ORF34	-0.3122	2.556e-08	0.000331
SP4	-0.3061	4.887e-08	0.000331
GLDC	0.3022	7.377e-08	0.000331
CHRNB1	0.3016	7.846e-08	0.000331
MDFI	0.2987	1.051e-07	0.000355
ERMAP	-0.2951	1.521e-07	0.000428
GALNT2	0.2927	1.947e-07	0.000435
RARB	-0.2921	2.061e-07	0.000435
C10ORF67	0.2902	2.481e-07	0.000466
LOC100216001	-0.2879	3.11e-07	0.000525

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	141
	T2	72
	T3	21
	T4	10

	Significant markers	N = 30
	pos. correlated	3
	neg. correlated	27

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
CLCA3P	-0.3475	2.473e-08	0.000144
NUP35	0.3443	3.371e-08	0.000144
PMCH	-0.3443	3.378e-08	0.000144
MPP7	-0.343	3.828e-08	0.000144
DKFZP586I1420	-0.3426	4.265e-08	0.000144
NCOA2	-0.3418	6.745e-08	0.000171
ATP6AP1L	-0.3366	7.096e-08	0.000171
TANC2	-0.3322	1.075e-07	0.000227
TMEM86B	-0.3293	1.405e-07	0.000264
MIR155HG	-0.3259	1.914e-07	0.000311

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	135
	N1	60

	Significant markers	N = 0

Clinical variable #5: 'PATHOLOGY_M_STAGE'

No 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 = 0

Clinical variable #6: 'RADIATION_THERAPY'

4 genes related to 'RADIATION_THERAPY'.

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


RADIATION_THERAPY	Labels	N
	NO	55
	YES	129

	Significant markers	N = 4
	Higher in YES	4
	Higher in NO	0

List of 4 genes differentially expressed by 'RADIATION_THERAPY'

Table S10. Get Full Table List of 4 genes differentially expressed by 'RADIATION_THERAPY'

	W(pos if higher in 'YES')	wilcoxontestP	Q	AUC
MGST2	5119	2.033e-06	0.0343	0.7215
PDCL	4989	1.318e-05	0.0753	0.7032
PHF17	4988	1.337e-05	0.0753	0.703
HLA-DRB1	4872	6.247e-05	0.264	0.6867

Clinical variable #7: 'HISTOLOGICAL_TYPE'

30 genes 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 genes differentially expressed by 'HISTOLOGICAL_TYPE'

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

	kruskal_wallis_P	Q
ATP10D	2.341e-22	3.96e-18
C10ORF108	4.945e-21	2.97e-17
TMEM117	5.275e-21	2.97e-17
GPR87	1.142e-20	4e-17
RGS12	1.417e-20	4e-17
HR	1.422e-20	4e-17
AKR1B10	3.213e-20	7.22e-17
BICD2	3.42e-20	7.22e-17
DST	6.725e-20	1.26e-16
ARNTL2	9.374e-20	1.45e-16

Clinical variable #8: 'NUMBER_PACK_YEARS_SMOKED'

No gene 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'

30 genes 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 = 30
	pos. correlated	24
	neg. correlated	6

List of top 10 genes differentially expressed by 'NUMBER_OF_LYMPH_NODES'

Table S15. Get Full Table List of top 10 genes significantly correlated to 'NUMBER_OF_LYMPH_NODES' by Spearman correlation test

	SpearmanCorr	corrP	Q
RCAN1	0.4028	1.412e-07	0.00239
NUAK1	0.3647	2.283e-06	0.0193
BCL9	0.3532	4.955e-06	0.0279
C3ORF71	0.3312	2e-05	0.0793
RNF20	-0.3266	2.653e-05	0.0793
PPARGC1A	0.3256	2.815e-05	0.0793
ZNF292	0.3203	3.845e-05	0.0841
DRAM1	0.3194	4.066e-05	0.0841
TXNDC6	0.3161	4.934e-05	0.0841
ZNF572	0.3134	5.764e-05	0.0841

Clinical variable #10: 'RACE'

30 genes related to 'RACE'.

Table S16. 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 = 30

List of top 10 genes differentially expressed by 'RACE'

Table S17. Get Full Table List of top 10 genes differentially expressed by 'RACE'

	kruskal_wallis_P	Q
SNX16	7.794e-07	0.0132
PDXDC1	4.374e-06	0.0275
IFNGR2	4.881e-06	0.0275
TLE1	1.486e-05	0.0519
NDUFS5	1.536e-05	0.0519
FAM22A	2.258e-05	0.0599
RNF151	2.483e-05	0.0599
HSD17B4	2.986e-05	0.0631
GPBAR1	3.821e-05	0.0701
FARSA	4.15e-05	0.0701

Clinical variable #11: 'ETHNICITY'

No gene related to 'ETHNICITY'.

Table S18. 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'

No gene related to 'WEIGHT_KG_AT_DIAGNOSIS'.

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


WEIGHT_KG_AT_DIAGNOSIS	Mean (SD)	73.04 (22)
	Significant markers	N = 0

Clinical variable #13: 'TUMOR_STATUS'

30 genes 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 = 30
	Higher in WITH TUMOR	30
	Higher in TUMOR FREE	0

List of top 10 genes differentially expressed by 'TUMOR_STATUS'

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

	W(pos if higher in 'WITH TUMOR')	wilcoxontestP	Q	AUC
PATL2	10931	2.574e-06	0.0402	0.6798
CCR5	10806	6.834e-06	0.0402	0.672
FAM35B2	5297	1.01e-05	0.0402	0.6689
SIT1	10747	1.069e-05	0.0402	0.6683
CHRM3	5376	1.472e-05	0.0402	0.6657
TIGIT	10702	1.494e-05	0.0402	0.6655
GDAP1	5398	1.731e-05	0.0402	0.6643
FASLG	10669	1.903e-05	0.0402	0.6635
C6ORF134	5444	2.419e-05	0.0454	0.6614
MPDU1	10614	2.833e-05	0.0466	0.6601

Clinical variable #14: 'NEOPLASM_HISTOLOGIC_GRADE'

30 genes 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 genes differentially expressed by 'NEOPLASM_HISTOLOGIC_GRADE'

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

	kruskal_wallis_P	Q
GMNN	3.108e-08	0.000525
MTF2	8.612e-08	0.000727
MRPS9	5.922e-07	0.00304
BRIX1	7.799e-07	0.00304
PPP1R7	8.989e-07	0.00304
PAIP1	1.241e-06	0.0035
MYL6	1.525e-06	0.00368
C9ORF40	1.855e-06	0.00392
LSM5	2.129e-06	0.004
ATP5G1	2.965e-06	0.00501

Clinical variable #15: 'TOBACCO_SMOKING_YEAR_STOPPED'

No gene 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 gene 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'

4 genes 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 = 4
	pos. correlated	3
	neg. correlated	1

List of 4 genes differentially expressed by 'TOBACCO_SMOKING_HISTORY'

Table S27. Get Full Table List of 4 genes significantly correlated to 'TOBACCO_SMOKING_HISTORY' by Spearman correlation test

	SpearmanCorr	corrP	Q
NKD2	-0.2599	1.97e-05	0.221
SCAP	0.2508	3.897e-05	0.221
QDPR	0.2494	4.31e-05	0.221
HPSE	0.2467	5.235e-05	0.221

Clinical variable #18: 'AGEBEGANSMOKINGINYEARS'

No gene 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 gene 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 gene 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 gene 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 genes 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	16
	neg. correlated	14

List of top 10 genes differentially expressed by 'PREGNANCY_SPONTANEOUS_ABORTION_COUNT'

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

	SpearmanCorr	corrP	Q
GPRIN1	-0.4424	2.026e-08	0.000197
TAF3	0.4406	2.335e-08	0.000197
POLR2D	0.4234	9.105e-08	0.000513
C8ORF77	-0.4066	3.216e-07	0.00133
ZBTB25	-0.4026	4.295e-07	0.00133
RSRC2	0.4036	4.8e-07	0.00133
ZNF592	-0.3992	5.495e-07	0.00133
ATL3	-0.3948	7.476e-07	0.00146
GOSR2	-0.3934	8.259e-07	0.00146
TRIM56	-0.3927	8.667e-07	0.00146

Clinical variable #23: 'PREGNANCIES_COUNT_LIVE_BIRTH'

30 genes 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 = 30
	pos. correlated	10
	neg. correlated	20

List of top 10 genes differentially expressed by 'PREGNANCIES_COUNT_LIVE_BIRTH'

Table S35. Get Full Table List of top 10 genes significantly correlated to 'PREGNANCIES_COUNT_LIVE_BIRTH' by Spearman correlation test

	SpearmanCorr	corrP	Q
POLE	-0.3279	5.561e-08	0.000939
ZNF488	-0.3204	1.144e-07	0.000966
PALM3	-0.3126	2.532e-07	0.00143
PGF	-0.2932	1.369e-06	0.00578
ZNF713	-0.2964	1.84e-06	0.00622
PDP2	-0.2861	2.515e-06	0.00708
LHX4	-0.2829	3.264e-06	0.00712
GPRIN1	-0.2826	3.371e-06	0.00712
MYO9B	-0.2778	4.991e-06	0.00862
NHEDC1	0.2769	5.376e-06	0.00862

Clinical variable #24: 'PREGNANCY_THERAPEUTIC_ABORTION_COUNT'

No gene 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 = 0

Clinical variable #25: 'PREGNANCIES_COUNT_ECTOPIC'

No gene related to 'PREGNANCIES_COUNT_ECTOPIC'.

Table S37. 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 S38. 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 S39. 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 = 30

List of top 10 genes differentially expressed by 'MENOPAUSE_STATUS'

Table S40. Get Full Table List of top 10 genes differentially expressed by 'MENOPAUSE_STATUS'

	kruskal_wallis_P	Q
C21ORF34	4.853e-06	0.082
CMTM7	2.168e-05	0.0831
SALL3	2.355e-05	0.0831
FBXW11	2.491e-05	0.0831
RARB	2.758e-05	0.0831
FLJ10213	2.951e-05	0.0831
CSGALNACT2	3.757e-05	0.0907
FBXO6	5.454e-05	0.11
MANBA	5.875e-05	0.11
SOX2	7.61e-05	0.124

Clinical variable #28: 'LYMPHOVASCULAR_INVOLVEMENT'

30 genes related to 'LYMPHOVASCULAR_INVOLVEMENT'.

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


LYMPHOVASCULAR_INVOLVEMENT	Labels	N
	ABSENT	72
	PRESENT	80

	Significant markers	N = 30
	Higher in PRESENT	30
	Higher in ABSENT	0

List of top 10 genes differentially expressed by 'LYMPHOVASCULAR_INVOLVEMENT'

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

	W(pos if higher in 'PRESENT')	wilcoxontestP	Q	AUC
MKRN2	c("4059", "1.369e-05")	c("4059", "1.369e-05")	0.229	0.7047
ZNF197	c("4012", "2.976e-05")	c("4012", "2.976e-05")	0.229	0.6965
HYAL3	c("3988", "4.375e-05")	c("3988", "4.375e-05")	0.229	0.6924
TMEM87B	c("1760", "5.423e-05")	c("1760", "5.423e-05")	0.229	0.6906
GAL3ST3	c("1830", "0.0001076")	c("1830", "0.0001076")	0.231	0.6823
CMTM6	c("3922", "0.0001214")	c("3922", "0.0001214")	0.231	0.6809
ANKRD31	c("3912", "0.0001411")	c("3912", "0.0001411")	0.231	0.6792
TMED7	c("3898", "0.0001736")	c("3898", "0.0001736")	0.231	0.6767
TMEM184C	c("3883", "0.0002162")	c("3883", "0.0002162")	0.231	0.6741
NAT1	c("3882", "0.0002194")	c("3882", "0.0002194")	0.231	0.674

Clinical variable #29: 'LYMPH_NODES_EXAMINED_HE_COUNT'

30 genes 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 = 30
	pos. correlated	24
	neg. correlated	6

List of top 10 genes differentially expressed by 'LYMPH_NODES_EXAMINED_HE_COUNT'

Table S44. Get Full Table List of top 10 genes significantly correlated to 'LYMPH_NODES_EXAMINED_HE_COUNT' by Spearman correlation test

	SpearmanCorr	corrP	Q
RCAN1	0.4028	1.412e-07	0.00239
NUAK1	0.3647	2.283e-06	0.0193
BCL9	0.3532	4.955e-06	0.0279
C3ORF71	0.3312	2e-05	0.0793
RNF20	-0.3266	2.653e-05	0.0793
PPARGC1A	0.3256	2.815e-05	0.0793
ZNF292	0.3203	3.845e-05	0.0841
DRAM1	0.3194	4.066e-05	0.0841
TXNDC6	0.3161	4.934e-05	0.0841
ZNF572	0.3134	5.764e-05	0.0841

Clinical variable #30: 'LYMPH_NODES_EXAMINED'

30 genes related to 'LYMPH_NODES_EXAMINED'.

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


LYMPH_NODES_EXAMINED	Mean (SD)	22.28 (13)
	Significant markers	N = 30
	pos. correlated	30
	neg. correlated	0

List of top 10 genes differentially expressed by 'LYMPH_NODES_EXAMINED'

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

	SpearmanCorr	corrP	Q
LOC643837	0.3129	1.894e-05	0.239
HDAC1	0.2956	5.618e-05	0.239
NIPA1	0.2955	5.643e-05	0.239
TTLL10	0.2901	7.806e-05	0.239
CCDC134	0.2867	9.537e-05	0.239
ULK1	0.2862	9.803e-05	0.239
GAR1	0.2854	0.0001079	0.239
MPP2	0.2843	0.000115	0.239
SNORD1C	0.2812	0.0001311	0.239
DPH5	0.2797	0.0001428	0.239

Clinical variable #31: 'KERATINIZATION_SQUAMOUS_CELL'

No gene related to 'KERATINIZATION_SQUAMOUS_CELL'.

Table S47. 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 = 0

Clinical variable #32: 'INITIAL_PATHOLOGIC_DX_YEAR'

30 genes related to 'INITIAL_PATHOLOGIC_DX_YEAR'.

Table S48. 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	2
	neg. correlated	28

List of top 10 genes differentially expressed by 'INITIAL_PATHOLOGIC_DX_YEAR'

Table S49. Get Full Table List of top 10 genes significantly correlated to 'INITIAL_PATHOLOGIC_DX_YEAR' by Spearman correlation test

	SpearmanCorr	corrP	Q
KLHL9	0.3635	5.885e-11	4.13e-07
MMD	-0.3628	6.409e-11	4.13e-07
RHOT2	-0.3617	7.343e-11	4.13e-07
DCDC1	-0.3525	2.365e-10	8.62e-07
C9ORF44	-0.3519	2.551e-10	8.62e-07
HIST1H1E	0.3482	4.01e-10	1.01e-06
LOC285456	-0.3479	4.17e-10	1.01e-06
MYLPF	-0.3422	8.357e-10	1.76e-06
TMEM86B	-0.3402	1.062e-09	1.99e-06
RSPH3	-0.3389	1.244e-09	2.1e-06

Clinical variable #33: 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'

No gene related to 'HISTORY_HORMONAL_CONTRACEPTIVES_USE'.

Table S50. 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 = 0

Clinical variable #34: 'HEIGHT_CM_AT_DIAGNOSIS'

No gene 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 = 0

Clinical variable #35: 'CORPUS_INVOLVEMENT'

No gene related to 'CORPUS_INVOLVEMENT'.

Table S52. 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 S53. 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 gene related to 'CERVIX_SUV_RESULTS'.

Table S54. 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 genes related to 'AGE_AT_DIAGNOSIS'.

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


AGE_AT_DIAGNOSIS	Mean (SD)	48.27 (14)
	Significant markers	N = 30
	pos. correlated	11
	neg. correlated	19

List of top 10 genes differentially expressed by 'AGE_AT_DIAGNOSIS'

Table S56. Get Full Table List of top 10 genes significantly correlated to 'AGE_AT_DIAGNOSIS' by Spearman correlation test

	SpearmanCorr	corrP	Q
C21ORF34	-0.3093	3.124e-08	0.000413
SP4	-0.3028	6.258e-08	0.000413
GLDC	0.2984	9.867e-08	0.000413
CHRNB1	0.2965	1.202e-07	0.000413
MDFI	0.2963	1.221e-07	0.000413
C10ORF67	0.2942	1.52e-07	0.000428
ERMAP	-0.2905	2.204e-07	0.000532
RARB	-0.2878	2.875e-07	0.000607
SERPINA1	0.284	4.186e-07	0.000783
GALNT2	0.2821	5.036e-07	0.000783

Clinical variable #39: 'CLINICAL_STAGE'

30 genes related to 'CLINICAL_STAGE'.

Table S57. 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 = 30

List of top 10 genes differentially expressed by 'CLINICAL_STAGE'

Table S58. Get Full Table List of top 10 genes differentially expressed by 'CLINICAL_STAGE'

	kruskal_wallis_P	Q
ARF4	8.113e-06	0.0364
C3ORF48	8.197e-06	0.0364
DPY30	8.729e-06	0.0364
ZNF322B	1.211e-05	0.0364
TMEM50A	1.319e-05	0.0364
PSMA3	1.41e-05	0.0364
WDR55	1.745e-05	0.0364
PDE1B	1.9e-05	0.0364
POU2F1	1.94e-05	0.0364
AFARP1	2.417e-05	0.0403

Methods & Data

Input

Expresson data file = CESC-TP.meth.by_min_clin_corr.data.txt
Clinical data file = CESC-TP.merged_data.txt
Number of patients = 307
Number of genes = 16894
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.

There are also useful links about clinical features.

CDE Browser

Data dictionary for clinical data

NCI wiki - Biospecimen and Clinical XSD Files Specification

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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