Uterine Corpus Endometrioid Carcinoma: Correlation between molecular cancer subtypes and selected clinical features
Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/Harvard Medical School)
Overview
Introduction

This pipeline computes the correlation between cancer subtypes identified by different molecular patterns and selected clinical features.

Summary

Testing the association between subtypes identified by 7 different clustering approaches and 5 clinical features across 373 patients, 26 significant findings detected with P value < 0.05.

  • CNMF clustering analysis on array-based mRNA expression data identified 4 subtypes that correlate to 'AGE',  'HISTOLOGICAL.TYPE',  'RADIATIONS.RADIATION.REGIMENINDICATION', and 'NEOADJUVANT.THERAPY'.

  • Consensus hierarchical clustering analysis on array-based mRNA expression data identified 3 subtypes that correlate to 'HISTOLOGICAL.TYPE' and 'NEOADJUVANT.THERAPY'.

  • 3 subtypes identified in current cancer cohort by 'METHLYATION CNMF'. These subtypes correlate to 'HISTOLOGICAL.TYPE' and 'NEOADJUVANT.THERAPY'.

  • CNMF clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that correlate to 'Time to Death',  'AGE',  'HISTOLOGICAL.TYPE',  'RADIATIONS.RADIATION.REGIMENINDICATION', and 'NEOADJUVANT.THERAPY'.

  • Consensus hierarchical clustering analysis on sequencing-based mRNA expression data identified 4 subtypes that correlate to 'Time to Death',  'AGE',  'HISTOLOGICAL.TYPE', and 'NEOADJUVANT.THERAPY'.

  • CNMF clustering analysis on sequencing-based miR expression data identified 3 subtypes that correlate to 'Time to Death',  'AGE',  'HISTOLOGICAL.TYPE',  'RADIATIONS.RADIATION.REGIMENINDICATION', and 'NEOADJUVANT.THERAPY'.

  • Consensus hierarchical clustering analysis on sequencing-based miR expression data identified 3 subtypes that correlate to 'Time to Death',  'AGE',  'HISTOLOGICAL.TYPE', and 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between subtypes identified by 7 different clustering approaches and 5 clinical features. Shown in the table are P values from statistical tests. Thresholded by P value < 0.05, 26 significant findings detected.

Clinical
Features
Time
to
Death
AGE HISTOLOGICAL
TYPE
RADIATIONS
RADIATION
REGIMENINDICATION
NEOADJUVANT
THERAPY
Statistical Tests logrank test ANOVA Chi-square test Fisher's exact test Fisher's exact test
mRNA CNMF subtypes 0.53 0.0107 4.81e-06 0.0317 0.0124
mRNA cHierClus subtypes 0.73 0.0598 1.45e-05 0.0666 0.0114
METHLYATION CNMF 0.0807 0.518 1.69e-10 0.611 0.0116
RNAseq CNMF subtypes 0.00713 0.00315 2.04e-23 0.0173 0.000161
RNAseq cHierClus subtypes 0.00623 0.000371 4.2e-24 0.0697 0.000172
MIRseq CNMF subtypes 0.012 0.00141 6.65e-23 0.0257 0.00453
MIRseq cHierClus subtypes 0.0138 0.0022 2.83e-19 0.00213 0.0567
Clustering Approach #1: 'mRNA CNMF subtypes'

Table S1.  Get Full Table Description of clustering approach #1: 'mRNA CNMF subtypes'

Cluster Labels 1 2 3 4
Number of samples 13 19 14 8
'mRNA CNMF subtypes' versus 'Time to Death'

P value = 0.53 (logrank test)

Table S2.  Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 54 7 6.0 - 133.2 (35.4)
subtype1 13 2 9.0 - 133.2 (39.0)
subtype2 19 3 6.0 - 113.2 (37.7)
subtype3 14 1 8.6 - 89.3 (30.9)
subtype4 8 1 6.4 - 65.5 (22.9)

Figure S1.  Get High-res Image Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'mRNA CNMF subtypes' versus 'AGE'

P value = 0.0107 (ANOVA)

Table S3.  Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 54 62.9 (11.8)
subtype1 13 65.1 (12.0)
subtype2 19 68.4 (9.1)
subtype3 14 58.2 (11.0)
subtype4 8 54.8 (12.9)

Figure S2.  Get High-res Image Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #2: 'AGE'

'mRNA CNMF subtypes' versus 'HISTOLOGICAL.TYPE'

P value = 4.81e-06 (Chi-square test)

Table S4.  Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3) MIXED SEROUS AND ENDOMETRIOID UTERINE SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 25 16 1 12
subtype1 4 8 0 1
subtype2 2 6 0 11
subtype3 12 1 1 0
subtype4 7 1 0 0

Figure S3.  Get High-res Image Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'mRNA CNMF subtypes' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.0317 (Fisher's exact test)

Table S5.  Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 25 29
subtype1 7 6
subtype2 13 6
subtype3 3 11
subtype4 2 6

Figure S4.  Get High-res Image Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'mRNA CNMF subtypes' versus 'NEOADJUVANT.THERAPY'

P value = 0.0124 (Fisher's exact test)

Table S6.  Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 36 18
subtype1 7 6
subtype2 9 10
subtype3 12 2
subtype4 8 0

Figure S5.  Get High-res Image Clustering Approach #1: 'mRNA CNMF subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

Clustering Approach #2: 'mRNA cHierClus subtypes'

Table S7.  Get Full Table Description of clustering approach #2: 'mRNA cHierClus subtypes'

Cluster Labels 1 2 3
Number of samples 20 15 19
'mRNA cHierClus subtypes' versus 'Time to Death'

P value = 0.73 (logrank test)

Table S8.  Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 54 7 6.0 - 133.2 (35.4)
subtype1 20 2 6.4 - 89.3 (29.8)
subtype2 15 2 9.0 - 133.2 (39.0)
subtype3 19 3 6.0 - 113.2 (37.7)

Figure S6.  Get High-res Image Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'mRNA cHierClus subtypes' versus 'AGE'

P value = 0.0598 (ANOVA)

Table S9.  Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 54 62.9 (11.8)
subtype1 20 58.2 (13.3)
subtype2 15 64.0 (10.6)
subtype3 19 67.1 (9.9)

Figure S7.  Get High-res Image Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #2: 'AGE'

'mRNA cHierClus subtypes' versus 'HISTOLOGICAL.TYPE'

P value = 1.45e-05 (Chi-square test)

Table S10.  Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3) MIXED SEROUS AND ENDOMETRIOID UTERINE SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 25 16 1 12
subtype1 17 2 1 0
subtype2 4 9 0 2
subtype3 4 5 0 10

Figure S8.  Get High-res Image Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'mRNA cHierClus subtypes' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.0666 (Fisher's exact test)

Table S11.  Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 25 29
subtype1 5 15
subtype2 9 6
subtype3 11 8

Figure S9.  Get High-res Image Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'mRNA cHierClus subtypes' versus 'NEOADJUVANT.THERAPY'

P value = 0.0114 (Fisher's exact test)

Table S12.  Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 36 18
subtype1 18 2
subtype2 9 6
subtype3 9 10

Figure S10.  Get High-res Image Clustering Approach #2: 'mRNA cHierClus subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

Clustering Approach #3: 'METHLYATION CNMF'

Table S13.  Get Full Table Description of clustering approach #3: 'METHLYATION CNMF'

Cluster Labels 1 2 3
Number of samples 38 50 29
'METHLYATION CNMF' versus 'Time to Death'

P value = 0.0807 (logrank test)

Table S14.  Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 117 10 0.9 - 133.2 (28.5)
subtype1 38 4 0.9 - 133.2 (26.5)
subtype2 50 6 1.3 - 98.2 (34.2)
subtype3 29 0 4.2 - 89.3 (24.5)

Figure S11.  Get High-res Image Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

'METHLYATION CNMF' versus 'AGE'

P value = 0.518 (ANOVA)

Table S15.  Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 117 63.1 (10.9)
subtype1 38 63.1 (12.3)
subtype2 50 64.2 (10.7)
subtype3 29 61.2 (9.2)

Figure S12.  Get High-res Image Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #2: 'AGE'

'METHLYATION CNMF' versus 'HISTOLOGICAL.TYPE'

P value = 1.69e-10 (Chi-square test)

Table S16.  Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3) MIXED SEROUS AND ENDOMETRIOID UTERINE SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 62 3 2 32 1 17
subtype1 8 1 1 10 1 17
subtype2 26 2 1 21 0 0
subtype3 28 0 0 1 0 0

Figure S13.  Get High-res Image Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'METHLYATION CNMF' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.611 (Fisher's exact test)

Table S17.  Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 54 63
subtype1 19 19
subtype2 24 26
subtype3 11 18

Figure S14.  Get High-res Image Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'METHLYATION CNMF' versus 'NEOADJUVANT.THERAPY'

P value = 0.0116 (Fisher's exact test)

Table S18.  Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 81 36
subtype1 20 18
subtype2 36 14
subtype3 25 4

Figure S15.  Get High-res Image Clustering Approach #3: 'METHLYATION CNMF' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

Clustering Approach #4: 'RNAseq CNMF subtypes'

Table S19.  Get Full Table Description of clustering approach #4: 'RNAseq CNMF subtypes'

Cluster Labels 1 2 3
Number of samples 95 83 88
'RNAseq CNMF subtypes' versus 'Time to Death'

P value = 0.00713 (logrank test)

Table S20.  Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 266 20 0.0 - 173.6 (20.2)
subtype1 95 13 0.5 - 133.2 (17.8)
subtype2 83 2 0.6 - 101.1 (21.4)
subtype3 88 5 0.0 - 173.6 (22.7)

Figure S16.  Get High-res Image Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'RNAseq CNMF subtypes' versus 'AGE'

P value = 0.00315 (ANOVA)

Table S21.  Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 266 63.1 (10.8)
subtype1 95 66.0 (10.6)
subtype2 83 62.4 (10.6)
subtype3 88 60.7 (10.6)

Figure S17.  Get High-res Image Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

'RNAseq CNMF subtypes' versus 'HISTOLOGICAL.TYPE'

P value = 2.04e-23 (Chi-square test)

Table S22.  Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3) MIXED SEROUS AND ENDOMETRIOID UTERINE SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 95 19 37 67 7 41
subtype1 8 2 6 32 6 41
subtype2 44 10 16 12 1 0
subtype3 43 7 15 23 0 0

Figure S18.  Get High-res Image Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'RNAseq CNMF subtypes' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.0173 (Fisher's exact test)

Table S23.  Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 99 167
subtype1 43 52
subtype2 21 62
subtype3 35 53

Figure S19.  Get High-res Image Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'RNAseq CNMF subtypes' versus 'NEOADJUVANT.THERAPY'

P value = 0.000161 (Fisher's exact test)

Table S24.  Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 183 83
subtype1 50 45
subtype2 64 19
subtype3 69 19

Figure S20.  Get High-res Image Clustering Approach #4: 'RNAseq CNMF subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

Clustering Approach #5: 'RNAseq cHierClus subtypes'

Table S25.  Get Full Table Description of clustering approach #5: 'RNAseq cHierClus subtypes'

Cluster Labels 1 2 3 4
Number of samples 92 53 41 80
'RNAseq cHierClus subtypes' versus 'Time to Death'

P value = 0.00623 (logrank test)

Table S26.  Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 266 20 0.0 - 173.6 (20.2)
subtype1 92 12 0.6 - 133.2 (17.7)
subtype2 53 4 0.0 - 173.6 (16.8)
subtype3 41 3 0.3 - 98.2 (27.4)
subtype4 80 1 0.6 - 101.1 (22.7)

Figure S21.  Get High-res Image Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'RNAseq cHierClus subtypes' versus 'AGE'

P value = 0.000371 (ANOVA)

Table S27.  Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 266 63.1 (10.8)
subtype1 92 66.3 (10.4)
subtype2 53 58.5 (10.3)
subtype3 41 63.0 (11.0)
subtype4 80 62.6 (10.5)

Figure S22.  Get High-res Image Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

'RNAseq cHierClus subtypes' versus 'HISTOLOGICAL.TYPE'

P value = 4.2e-24 (Chi-square test)

Table S28.  Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3) MIXED SEROUS AND ENDOMETRIOID UTERINE SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 95 19 37 67 7 41
subtype1 8 1 5 31 6 41
subtype2 31 4 10 8 0 0
subtype3 13 4 7 17 0 0
subtype4 43 10 15 11 1 0

Figure S23.  Get High-res Image Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'RNAseq cHierClus subtypes' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.0697 (Fisher's exact test)

Table S29.  Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 99 167
subtype1 43 49
subtype2 18 35
subtype3 16 25
subtype4 22 58

Figure S24.  Get High-res Image Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'RNAseq cHierClus subtypes' versus 'NEOADJUVANT.THERAPY'

P value = 0.000172 (Fisher's exact test)

Table S30.  Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 183 83
subtype1 48 44
subtype2 43 10
subtype3 28 13
subtype4 64 16

Figure S25.  Get High-res Image Clustering Approach #5: 'RNAseq cHierClus subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

Clustering Approach #6: 'MIRseq CNMF subtypes'

Table S31.  Get Full Table Description of clustering approach #6: 'MIRseq CNMF subtypes'

Cluster Labels 1 2 3
Number of samples 107 131 121
'MIRseq CNMF subtypes' versus 'Time to Death'

P value = 0.012 (logrank test)

Table S32.  Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 357 27 0.0 - 187.1 (16.9)
subtype1 106 12 0.0 - 187.1 (15.3)
subtype2 130 3 0.1 - 101.1 (16.6)
subtype3 121 12 0.5 - 173.6 (22.6)

Figure S26.  Get High-res Image Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'MIRseq CNMF subtypes' versus 'AGE'

P value = 0.00141 (ANOVA)

Table S33.  Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 359 63.0 (11.1)
subtype1 107 66.2 (10.1)
subtype2 131 61.5 (11.5)
subtype3 121 61.8 (10.9)

Figure S27.  Get High-res Image Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

'MIRseq CNMF subtypes' versus 'HISTOLOGICAL.TYPE'

P value = 6.65e-23 (Chi-square test)

Table S34.  Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3) MIXED SEROUS AND ENDOMETRIOID UTERINE SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 99 34 57 108 13 48
subtype1 5 5 10 40 8 39
subtype2 57 20 30 23 1 0
subtype3 37 9 17 45 4 9

Figure S28.  Get High-res Image Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'MIRseq CNMF subtypes' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.0257 (Fisher's exact test)

Table S35.  Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 121 238
subtype1 44 63
subtype2 33 98
subtype3 44 77

Figure S29.  Get High-res Image Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'MIRseq CNMF subtypes' versus 'NEOADJUVANT.THERAPY'

P value = 0.00453 (Fisher's exact test)

Table S36.  Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 265 94
subtype1 68 39
subtype2 108 23
subtype3 89 32

Figure S30.  Get High-res Image Clustering Approach #6: 'MIRseq CNMF subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

Clustering Approach #7: 'MIRseq cHierClus subtypes'

Table S37.  Get Full Table Description of clustering approach #7: 'MIRseq cHierClus subtypes'

Cluster Labels 1 2 3
Number of samples 112 169 78
'MIRseq cHierClus subtypes' versus 'Time to Death'

P value = 0.0138 (logrank test)

Table S38.  Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 357 27 0.0 - 187.1 (16.9)
subtype1 112 2 0.1 - 89.3 (17.0)
subtype2 167 17 0.0 - 187.1 (16.8)
subtype3 78 8 0.6 - 173.6 (18.9)

Figure S31.  Get High-res Image Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'MIRseq cHierClus subtypes' versus 'AGE'

P value = 0.0022 (ANOVA)

Table S39.  Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 359 63.0 (11.1)
subtype1 112 62.9 (10.3)
subtype2 169 64.7 (10.9)
subtype3 78 59.4 (11.6)

Figure S32.  Get High-res Image Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

'MIRseq cHierClus subtypes' versus 'HISTOLOGICAL.TYPE'

P value = 2.83e-19 (Chi-square test)

Table S40.  Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2) ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3) MIXED SEROUS AND ENDOMETRIOID UTERINE SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL 99 34 57 108 13 48
subtype1 43 18 26 21 2 2
subtype2 18 9 20 65 11 46
subtype3 38 7 11 22 0 0

Figure S33.  Get High-res Image Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'MIRseq cHierClus subtypes' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.00213 (Fisher's exact test)

Table S41.  Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 121 238
subtype1 32 80
subtype2 72 97
subtype3 17 61

Figure S34.  Get High-res Image Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'MIRseq cHierClus subtypes' versus 'NEOADJUVANT.THERAPY'

P value = 0.0567 (Fisher's exact test)

Table S42.  Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 265 94
subtype1 90 22
subtype2 115 54
subtype3 60 18

Figure S35.  Get High-res Image Clustering Approach #7: 'MIRseq cHierClus subtypes' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

Methods & Data
Input
  • Cluster data file = UCEC.mergedcluster.txt

  • Clinical data file = UCEC.clin.merged.picked.txt

  • Number of patients = 373

  • Number of clustering approaches = 7

  • Number of selected clinical features = 5

  • Exclude small clusters that include fewer than K patients, K = 3

Clustering approaches
CNMF clustering

consensus non-negative matrix factorization clustering approach (Brunet et al. 2004)

Consensus hierarchical clustering

Resampling-based clustering method (Monti et al. 2003)

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

ANOVA analysis

For continuous numerical clinical features, one-way analysis of variance (Howell 2002) was applied to compare the clinical values between tumor subtypes using 'anova' function in R

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.test' function in R

Fisher's exact test

For binary clinical features, two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

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References
[1] Brunet et al., Metagenes and molecular pattern discovery using matrix factorization, PNAS 101(12):4164-9 (2004)
[3] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[5] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[6] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)
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