Cervical Squamous Cell 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 4 different clustering approaches and 4 clinical features across 32 patients, one significant finding detected with P value < 0.05.

  • 3 subtypes identified in current cancer cohort by 'CN CNMF'. These subtypes do not correlate to any clinical features.

  • 3 subtypes identified in current cancer cohort by 'METHLYATION CNMF'. These subtypes correlate to 'Time to Death'.

  • CNMF clustering analysis on sequencing-based miR expression data identified 3 subtypes that do not correlate to any clinical features.

  • Consensus hierarchical clustering analysis on sequencing-based miR expression data identified 3 subtypes that do not correlate to any clinical features.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between subtypes identified by 4 different clustering approaches and 4 clinical features. Shown in the table are P values from statistical tests. Thresholded by P value < 0.05, one significant finding detected.

Clinical
Features
Time
to
Death
AGE RADIATIONS
RADIATION
REGIMENINDICATION
NEOADJUVANT
THERAPY
Statistical Tests logrank test ANOVA Fisher's exact test Fisher's exact test
CN CNMF 0.317 0.647 0.801 0.801
METHLYATION CNMF 0.0358 0.618 0.721 0.397
MIRseq CNMF subtypes 0.956 0.42 1 0.66
MIRseq cHierClus subtypes 0.183 0.259 0.856 1
Clustering Approach #1: 'CN CNMF'

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

Cluster Labels 1 2 3
Number of samples 10 4 12
'CN CNMF' versus 'Time to Death'

P value = 0.317 (logrank test)

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

nPatients nDeath Duration Range (Median), Month
ALL 25 1 0.1 - 95.1 (2.7)
subtype1 9 0 0.3 - 70.8 (2.7)
subtype2 4 0 1.2 - 69.9 (3.6)
subtype3 12 1 0.1 - 95.1 (3.8)

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

'CN CNMF' versus 'AGE'

P value = 0.647 (ANOVA)

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

nPatients Mean (Std.Dev)
ALL 26 48.5 (11.8)
subtype1 10 46.8 (10.4)
subtype2 4 53.5 (6.9)
subtype3 12 48.2 (14.3)

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

'CN CNMF' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.801 (Fisher's exact test)

Table S4.  Clustering Approach #1: 'CN CNMF' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 4 22
subtype1 1 9
subtype2 1 3
subtype3 2 10

Figure S3.  Get High-res Image Clustering Approach #1: 'CN CNMF' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'CN CNMF' versus 'NEOADJUVANT.THERAPY'

P value = 0.801 (Fisher's exact test)

Table S5.  Clustering Approach #1: 'CN CNMF' versus Clinical Feature #4: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 4 22
subtype1 1 9
subtype2 1 3
subtype3 2 10

Figure S4.  Get High-res Image Clustering Approach #1: 'CN CNMF' versus Clinical Feature #4: 'NEOADJUVANT.THERAPY'

Clustering Approach #2: 'METHLYATION CNMF'

Table S6.  Get Full Table Description of clustering approach #2: 'METHLYATION CNMF'

Cluster Labels 1 2 3
Number of samples 12 17 3
'METHLYATION CNMF' versus 'Time to Death'

P value = 0.0358 (logrank test)

Table S7.  Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 31 4 0.1 - 101.8 (5.8)
subtype1 12 0 0.6 - 101.8 (16.2)
subtype2 16 4 0.1 - 95.1 (4.3)
subtype3 3 0 1.2 - 5.8 (2.2)

Figure S5.  Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

'METHLYATION CNMF' versus 'AGE'

P value = 0.618 (ANOVA)

Table S8.  Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 32 49.9 (12.7)
subtype1 12 52.8 (11.2)
subtype2 17 48.4 (13.5)
subtype3 3 47.0 (16.5)

Figure S6.  Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #2: 'AGE'

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

P value = 0.721 (Fisher's exact test)

Table S9.  Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 8 24
subtype1 2 10
subtype2 5 12
subtype3 1 2

Figure S7.  Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'METHLYATION CNMF' versus 'NEOADJUVANT.THERAPY'

P value = 0.397 (Fisher's exact test)

Table S10.  Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #4: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 8 24
subtype1 2 10
subtype2 6 11
subtype3 0 3

Figure S8.  Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #4: 'NEOADJUVANT.THERAPY'

Clustering Approach #3: 'MIRseq CNMF subtypes'

Table S11.  Get Full Table Description of clustering approach #3: 'MIRseq CNMF subtypes'

Cluster Labels 1 2 3
Number of samples 11 14 7
'MIRseq CNMF subtypes' versus 'Time to Death'

P value = 0.956 (logrank test)

Table S12.  Clustering Approach #3: 'MIRseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 31 4 0.1 - 101.8 (5.8)
subtype1 11 2 0.1 - 95.1 (12.4)
subtype2 13 2 0.6 - 101.8 (5.5)
subtype3 7 0 1.0 - 6.0 (1.2)

Figure S9.  Get High-res Image Clustering Approach #3: 'MIRseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'MIRseq CNMF subtypes' versus 'AGE'

P value = 0.42 (ANOVA)

Table S13.  Clustering Approach #3: 'MIRseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 32 49.9 (12.7)
subtype1 11 47.5 (12.6)
subtype2 14 53.3 (11.9)
subtype3 7 46.9 (14.6)

Figure S10.  Get High-res Image Clustering Approach #3: 'MIRseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

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

P value = 1 (Fisher's exact test)

Table S14.  Clustering Approach #3: 'MIRseq CNMF subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 8 24
subtype1 3 8
subtype2 3 11
subtype3 2 5

Figure S11.  Get High-res Image Clustering Approach #3: 'MIRseq CNMF subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'MIRseq CNMF subtypes' versus 'NEOADJUVANT.THERAPY'

P value = 0.66 (Fisher's exact test)

Table S15.  Clustering Approach #3: 'MIRseq CNMF subtypes' versus Clinical Feature #4: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 8 24
subtype1 4 7
subtype2 3 11
subtype3 1 6

Figure S12.  Get High-res Image Clustering Approach #3: 'MIRseq CNMF subtypes' versus Clinical Feature #4: 'NEOADJUVANT.THERAPY'

Clustering Approach #4: 'MIRseq cHierClus subtypes'

Table S16.  Get Full Table Description of clustering approach #4: 'MIRseq cHierClus subtypes'

Cluster Labels 1 2 3
Number of samples 3 18 11
'MIRseq cHierClus subtypes' versus 'Time to Death'

P value = 0.183 (logrank test)

Table S17.  Clustering Approach #4: 'MIRseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 31 4 0.1 - 101.8 (5.8)
subtype1 3 0 1.2 - 6.0 (2.2)
subtype2 18 4 0.3 - 101.8 (7.3)
subtype3 10 0 0.1 - 95.1 (4.8)

Figure S13.  Get High-res Image Clustering Approach #4: 'MIRseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'MIRseq cHierClus subtypes' versus 'AGE'

P value = 0.259 (ANOVA)

Table S18.  Clustering Approach #4: 'MIRseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 32 49.9 (12.7)
subtype1 3 43.0 (13.7)
subtype2 18 53.1 (13.6)
subtype3 11 46.5 (10.2)

Figure S14.  Get High-res Image Clustering Approach #4: 'MIRseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

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

P value = 0.856 (Fisher's exact test)

Table S19.  Clustering Approach #4: 'MIRseq cHierClus subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients NO YES
ALL 8 24
subtype1 1 2
subtype2 5 13
subtype3 2 9

Figure S15.  Get High-res Image Clustering Approach #4: 'MIRseq cHierClus subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'MIRseq cHierClus subtypes' versus 'NEOADJUVANT.THERAPY'

P value = 1 (Fisher's exact test)

Table S20.  Clustering Approach #4: 'MIRseq cHierClus subtypes' versus Clinical Feature #4: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 8 24
subtype1 1 2
subtype2 4 14
subtype3 3 8

Figure S16.  Get High-res Image Clustering Approach #4: 'MIRseq cHierClus subtypes' versus Clinical Feature #4: 'NEOADJUVANT.THERAPY'

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

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

  • Number of patients = 32

  • Number of clustering approaches = 4

  • Number of selected clinical features = 4

  • 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

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

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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] 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)