Correlation between aggregated molecular cancer subtypes and selected clinical features

Cervical Squamous Cell Carcinoma (Primary solid tumor)

23 May 2013 | analyses__2013_05_23

Maintainer Information

Citation Information

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between aggregated molecular cancer subtypes and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1PR7T0F

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 8 different clustering approaches and 8 clinical features across 48 patients, no significant finding detected with P value < 0.05 and Q value < 0.25.

3 subtypes identified in current cancer cohort by 'Copy Number Ratio CNMF subtypes'. These subtypes do not correlate to any clinical features.
3 subtypes identified in current cancer cohort by 'METHLYATION CNMF'. These subtypes do not correlate to any clinical features.
CNMF clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that do not correlate to any clinical features.
Consensus hierarchical clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that do not correlate to any clinical features.
4 subtypes identified in current cancer cohort by 'MIRSEQ CNMF'. These subtypes do not correlate to any clinical features.
2 subtypes identified in current cancer cohort by 'MIRSEQ CHIERARCHICAL'. These subtypes do not correlate to any clinical features.
3 subtypes identified in current cancer cohort by 'MIRseq Mature CNMF subtypes'. These subtypes do not correlate to any clinical features.
3 subtypes identified in current cancer cohort by 'MIRseq Mature cHierClus subtypes'. These subtypes 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 8 different clustering approaches and 8 clinical features. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, no significant finding detected.


Clinical Features	Time to Death	AGE	RADIATIONS RADIATION REGIMENINDICATION	NUMBERPACKYEARSSMOKED	DISTANT METASTASIS	LYMPH NODE METASTASIS	NUMBER OF LYMPH NODES	TUMOR STAGECODE
Statistical Tests	logrank test	ANOVA	Fisher's exact test	ANOVA	Fisher's exact test	Fisher's exact test	ANOVA	ANOVA
Copy Number Ratio CNMF subtypes	0.251 (1.00)	0.687 (1.00)	0.301 (1.00)	0.641 (1.00)	0.324 (1.00)	0.583 (1.00)	0.202 (1.00)
METHLYATION CNMF	0.482 (1.00)	0.979 (1.00)	0.59 (1.00)	0.402 (1.00)	0.315 (1.00)	0.316 (1.00)	0.264 (1.00)
RNAseq CNMF subtypes	0.977 (1.00)	0.589 (1.00)	0.424 (1.00)	0.412 (1.00)	0.0517 (1.00)	0.9 (1.00)	0.18 (1.00)
RNAseq cHierClus subtypes	0.577 (1.00)	0.769 (1.00)	0.678 (1.00)	0.403 (1.00)	0.0752 (1.00)	1 (1.00)	0.8 (1.00)
MIRSEQ CNMF	0.144 (1.00)	0.0899 (1.00)	0.763 (1.00)	0.606 (1.00)	0.459 (1.00)	0.366 (1.00)	0.571 (1.00)
MIRSEQ CHIERARCHICAL	0.479 (1.00)	0.854 (1.00)	1 (1.00)	0.403 (1.00)	0.442 (1.00)	0.716 (1.00)	0.449 (1.00)
MIRseq Mature CNMF subtypes	0.83 (1.00)	0.181 (1.00)	0.921 (1.00)	0.623 (1.00)	0.212 (1.00)	0.78 (1.00)	0.705 (1.00)
MIRseq Mature cHierClus subtypes	0.52 (1.00)	0.186 (1.00)	0.911 (1.00)	0.27 (1.00)	0.416 (1.00)	0.905 (1.00)	0.436 (1.00)

Clustering Approach #1: 'Copy Number Ratio CNMF subtypes'

Table S1. Get Full Table Description of clustering approach #1: 'Copy Number Ratio CNMF subtypes'

Cluster Labels	1	2	3
Number of samples	18	7	17

'Copy Number Ratio CNMF subtypes' versus 'Time to Death'

P value = 0.251 (logrank test), Q value = 1

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

	nPatients	nDeath	Duration Range (Median), Month
ALL	41	7	0.1 - 177.0 (5.5)
subtype1	17	2	0.3 - 78.3 (5.5)
subtype2	7	4	1.8 - 70.8 (35.6)
subtype3	17	1	0.1 - 177.0 (2.4)

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

'Copy Number Ratio CNMF subtypes' versus 'AGE'

P value = 0.687 (ANOVA), Q value = 1

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

	nPatients	Mean (Std.Dev)
ALL	42	46.7 (12.2)
subtype1	18	48.3 (10.4)
subtype2	7	43.6 (9.2)
subtype3	17	46.2 (15.2)

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

'Copy Number Ratio CNMF subtypes' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.301 (Fisher's exact test), Q value = 1

Table S4. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients	NO	YES
ALL	13	29
subtype1	5	13
subtype2	4	3
subtype3	4	13

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

'Copy Number Ratio CNMF subtypes' versus 'NUMBERPACKYEARSSMOKED'

P value = 0.641 (ANOVA), Q value = 1

Table S5. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

	nPatients	Mean (Std.Dev)
ALL	14	20.6 (13.1)
subtype1	3	14.0 (5.3)
subtype2	3	23.7 (12.1)
subtype3	8	21.9 (15.6)

Figure S4. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

'Copy Number Ratio CNMF subtypes' versus 'DISTANT.METASTASIS'

P value = 0.324 (Fisher's exact test), Q value = 1

Table S6. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	MX
ALL	23	14
subtype1	12	5
subtype2	4	1
subtype3	7	8

Figure S5. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'Copy Number Ratio CNMF subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 0.583 (Fisher's exact test), Q value = 1

Table S7. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1
ALL	24	14
subtype1	11	6
subtype2	2	3
subtype3	11	5

Figure S6. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'Copy Number Ratio CNMF subtypes' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.202 (ANOVA), Q value = 1

Table S8. Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	36	0.6 (1.0)
subtype1	16	0.6 (1.1)
subtype2	5	1.2 (1.6)
subtype3	15	0.3 (0.6)

Figure S7. Get High-res Image Clustering Approach #1: 'Copy Number Ratio CNMF subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #2: 'METHLYATION CNMF'

Table S9. Get Full Table Description of clustering approach #2: 'METHLYATION CNMF'

Cluster Labels	1	2	3
Number of samples	25	16	7

'METHLYATION CNMF' versus 'Time to Death'

P value = 0.482 (logrank test), Q value = 1

Table S10. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	10	0.1 - 177.0 (6.0)
subtype1	24	7	0.1 - 177.0 (5.9)
subtype2	16	2	0.6 - 101.8 (14.3)
subtype3	7	1	0.7 - 53.1 (2.2)

Figure S8. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #1: 'Time to Death'

'METHLYATION CNMF' versus 'AGE'

P value = 0.979 (ANOVA), Q value = 1

Table S11. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	48	47.8 (12.9)
subtype1	25	47.5 (12.6)
subtype2	16	48.4 (14.6)
subtype3	7	47.7 (11.6)

Figure S9. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #2: 'AGE'

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

P value = 0.59 (Fisher's exact test), Q value = 1

Table S12. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients	NO	YES
ALL	16	32
subtype1	7	18
subtype2	7	9
subtype3	2	5

Figure S10. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'METHLYATION CNMF' versus 'NUMBERPACKYEARSSMOKED'

P value = 0.402 (ANOVA), Q value = 1

Table S13. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

	nPatients	Mean (Std.Dev)
ALL	14	20.6 (13.1)
subtype1	8	20.4 (13.9)
subtype2	3	13.3 (2.9)
subtype3	3	28.3 (16.1)

Figure S11. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

'METHLYATION CNMF' versus 'DISTANT.METASTASIS'

P value = 0.315 (Fisher's exact test), Q value = 1

Table S14. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	MX
ALL	29	14
subtype1	15	6
subtype2	11	4
subtype3	3	4

Figure S12. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'METHLYATION CNMF' versus 'LYMPH.NODE.METASTASIS'

P value = 0.316 (Fisher's exact test), Q value = 1

Table S15. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1
ALL	27	17
subtype1	11	11
subtype2	11	4
subtype3	5	2

Figure S13. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'METHLYATION CNMF' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.264 (ANOVA), Q value = 1

Table S16. Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	42	1.1 (2.8)
subtype1	22	1.8 (3.7)
subtype2	14	0.4 (1.1)
subtype3	6	0.3 (0.5)

Figure S14. Get High-res Image Clustering Approach #2: 'METHLYATION CNMF' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #3: 'RNAseq CNMF subtypes'

Table S17. Get Full Table Description of clustering approach #3: 'RNAseq CNMF subtypes'

Cluster Labels	1	2	3
Number of samples	26	10	7

'RNAseq CNMF subtypes' versus 'Time to Death'

P value = 0.977 (logrank test), Q value = 1

Table S18. Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	42	8	0.1 - 177.0 (5.9)
subtype1	26	4	0.1 - 177.0 (2.7)
subtype2	9	3	1.0 - 101.8 (30.4)
subtype3	7	1	0.7 - 53.1 (7.9)

Figure S15. Get High-res Image Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'RNAseq CNMF subtypes' versus 'AGE'

P value = 0.589 (ANOVA), Q value = 1

Table S19. Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	43	46.6 (11.6)
subtype1	26	48.1 (12.5)
subtype2	10	44.6 (10.6)
subtype3	7	44.0 (9.5)

Figure S16. Get High-res Image Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #2: 'AGE'

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

P value = 0.424 (Fisher's exact test), Q value = 1

Table S20. Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients	NO	YES
ALL	14	29
subtype1	7	19
subtype2	5	5
subtype3	2	5

Figure S17. Get High-res Image Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'RNAseq CNMF subtypes' versus 'NUMBERPACKYEARSSMOKED'

P value = 0.412 (ANOVA), Q value = 1

Table S21. Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

	nPatients	Mean (Std.Dev)
ALL	14	20.6 (13.1)
subtype1	9	18.6 (13.1)
subtype2	2	18.0 (9.9)
subtype3	3	28.3 (16.1)

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

'RNAseq CNMF subtypes' versus 'DISTANT.METASTASIS'

P value = 0.0517 (Fisher's exact test), Q value = 1

Table S22. Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	MX
ALL	25	13
subtype1	15	9
subtype2	7	0
subtype3	3	4

Figure S19. Get High-res Image Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'RNAseq CNMF subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 0.9 (Fisher's exact test), Q value = 1

Table S23. Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1
ALL	24	15
subtype1	15	10
subtype2	4	3
subtype3	5	2

Figure S20. Get High-res Image Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'RNAseq CNMF subtypes' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.18 (ANOVA), Q value = 1

Table S24. Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	37	1.0 (2.7)
subtype1	24	0.7 (1.2)
subtype2	7	2.7 (5.9)
subtype3	6	0.3 (0.5)

Figure S21. Get High-res Image Clustering Approach #3: 'RNAseq CNMF subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #4: 'RNAseq cHierClus subtypes'

Table S25. Get Full Table Description of clustering approach #4: 'RNAseq cHierClus subtypes'

Cluster Labels	1	2	3
Number of samples	6	31	6

'RNAseq cHierClus subtypes' versus 'Time to Death'

P value = 0.577 (logrank test), Q value = 1

Table S26. Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	42	8	0.1 - 177.0 (5.9)
subtype1	5	0	1.0 - 101.8 (12.4)
subtype2	31	7	0.1 - 177.0 (5.5)
subtype3	6	1	0.7 - 53.1 (5.0)

Figure S22. Get High-res Image Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'RNAseq cHierClus subtypes' versus 'AGE'

P value = 0.769 (ANOVA), Q value = 1

Table S27. Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	43	46.6 (11.6)
subtype1	6	49.7 (7.2)
subtype2	31	46.4 (12.6)
subtype3	6	45.0 (10.0)

Figure S23. Get High-res Image Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #2: 'AGE'

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

P value = 0.678 (Fisher's exact test), Q value = 1

Table S28. Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients	NO	YES
ALL	14	29
subtype1	3	3
subtype2	9	22
subtype3	2	4

Figure S24. Get High-res Image Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'RNAseq cHierClus subtypes' versus 'NUMBERPACKYEARSSMOKED'

P value = 0.403 (ANOVA), Q value = 1

Table S29. Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

	nPatients	Mean (Std.Dev)
ALL	14	20.6 (13.1)
subtype2	11	18.5 (12.1)
subtype3	3	28.3 (16.1)

Figure S25. Get High-res Image Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

'RNAseq cHierClus subtypes' versus 'DISTANT.METASTASIS'

P value = 0.0752 (Fisher's exact test), Q value = 1

Table S30. Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	MX
ALL	25	13
subtype1	5	0
subtype2	18	9
subtype3	2	4

Figure S26. Get High-res Image Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'RNAseq cHierClus subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 1 (Fisher's exact test), Q value = 1

Table S31. Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1
ALL	24	15
subtype1	3	2
subtype2	17	11
subtype3	4	2

Figure S27. Get High-res Image Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'RNAseq cHierClus subtypes' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.8 (ANOVA), Q value = 1

Table S32. Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	37	1.0 (2.7)
subtype1	5	0.6 (0.9)
subtype2	27	1.2 (3.2)
subtype3	5	0.4 (0.5)

Figure S28. Get High-res Image Clustering Approach #4: 'RNAseq cHierClus subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #5: 'MIRSEQ CNMF'

Table S33. Get Full Table Description of clustering approach #5: 'MIRSEQ CNMF'

Cluster Labels	1	2	3	4
Number of samples	22	15	3	8

'MIRSEQ CNMF' versus 'Time to Death'

P value = 0.144 (logrank test), Q value = 1

Table S34. Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	10	0.1 - 177.0 (6.0)
subtype1	21	5	0.3 - 177.0 (5.8)
subtype2	15	3	0.1 - 95.1 (6.9)
subtype3	3	1	0.6 - 8.8 (3.5)
subtype4	8	1	0.7 - 78.3 (5.0)

Figure S29. Get High-res Image Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #1: 'Time to Death'

'MIRSEQ CNMF' versus 'AGE'

P value = 0.0899 (ANOVA), Q value = 1

Table S35. Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	48	47.8 (12.9)
subtype1	22	50.8 (13.2)
subtype2	15	42.5 (8.9)
subtype3	3	59.3 (21.4)
subtype4	8	45.5 (12.5)

Figure S30. Get High-res Image Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #2: 'AGE'

'MIRSEQ CNMF' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 0.763 (Fisher's exact test), Q value = 1

Table S36. Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients	NO	YES
ALL	16	32
subtype1	7	15
subtype2	6	9
subtype3	0	3
subtype4	3	5

Figure S31. Get High-res Image Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'MIRSEQ CNMF' versus 'NUMBERPACKYEARSSMOKED'

P value = 0.606 (ANOVA), Q value = 1

Table S37. Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

	nPatients	Mean (Std.Dev)
ALL	14	20.6 (13.1)
subtype1	4	18.0 (5.7)
subtype2	6	20.2 (16.0)
subtype3	1	10.0 (NA)
subtype4	3	28.3 (16.1)

Figure S32. Get High-res Image Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

'MIRSEQ CNMF' versus 'DISTANT.METASTASIS'

P value = 0.459 (Fisher's exact test), Q value = 1

Table S38. Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	MX
ALL	29	14
subtype1	13	7
subtype2	10	2
subtype3	2	1
subtype4	4	4

Figure S33. Get High-res Image Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'MIRSEQ CNMF' versus 'LYMPH.NODE.METASTASIS'

P value = 0.366 (Fisher's exact test), Q value = 1

Table S39. Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1
ALL	27	17
subtype1	12	8
subtype2	6	7
subtype3	3	0
subtype4	6	2

Figure S34. Get High-res Image Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'MIRSEQ CNMF' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.571 (ANOVA), Q value = 1

Table S40. Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	42	1.1 (2.8)
subtype1	20	1.1 (2.1)
subtype2	12	1.9 (4.5)
subtype3	3	0.0 (0.0)
subtype4	7	0.3 (0.5)

Figure S35. Get High-res Image Clustering Approach #5: 'MIRSEQ CNMF' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #6: 'MIRSEQ CHIERARCHICAL'

Table S41. Get Full Table Description of clustering approach #6: 'MIRSEQ CHIERARCHICAL'

Cluster Labels	1	2
Number of samples	39	9

'MIRSEQ CHIERARCHICAL' versus 'Time to Death'

P value = 0.479 (logrank test), Q value = 1

Table S42. Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	10	0.1 - 177.0 (6.0)
subtype1	38	8	0.1 - 177.0 (6.4)
subtype2	9	2	0.7 - 53.1 (6.0)

Figure S36. Get High-res Image Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #1: 'Time to Death'

'MIRSEQ CHIERARCHICAL' versus 'AGE'

P value = 0.854 (t-test), Q value = 1

Table S43. Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	48	47.8 (12.9)
subtype1	39	48.0 (13.6)
subtype2	9	47.2 (10.1)

Figure S37. Get High-res Image Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #2: 'AGE'

'MIRSEQ CHIERARCHICAL' versus 'RADIATIONS.RADIATION.REGIMENINDICATION'

P value = 1 (Fisher's exact test), Q value = 1

Table S44. Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients	NO	YES
ALL	16	32
subtype1	13	26
subtype2	3	6

Figure S38. Get High-res Image Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'MIRSEQ CHIERARCHICAL' versus 'NUMBERPACKYEARSSMOKED'

P value = 0.403 (t-test), Q value = 1

Table S45. Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

	nPatients	Mean (Std.Dev)
ALL	14	20.6 (13.1)
subtype1	11	18.5 (12.1)
subtype2	3	28.3 (16.1)

Figure S39. Get High-res Image Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

'MIRSEQ CHIERARCHICAL' versus 'DISTANT.METASTASIS'

P value = 0.442 (Fisher's exact test), Q value = 1

Table S46. Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	MX
ALL	29	14
subtype1	24	10
subtype2	5	4

Figure S40. Get High-res Image Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'MIRSEQ CHIERARCHICAL' versus 'LYMPH.NODE.METASTASIS'

P value = 0.716 (Fisher's exact test), Q value = 1

Table S47. Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1
ALL	27	17
subtype1	22	13
subtype2	5	4

Figure S41. Get High-res Image Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'MIRSEQ CHIERARCHICAL' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.449 (t-test), Q value = 1

Table S48. Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	42	1.1 (2.8)
subtype1	34	0.8 (1.7)
subtype2	8	2.4 (5.5)

Figure S42. Get High-res Image Clustering Approach #6: 'MIRSEQ CHIERARCHICAL' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #7: 'MIRseq Mature CNMF subtypes'

Table S49. Get Full Table Description of clustering approach #7: 'MIRseq Mature CNMF subtypes'

Cluster Labels	1	2	3
Number of samples	22	18	8

'MIRseq Mature CNMF subtypes' versus 'Time to Death'

P value = 0.83 (logrank test), Q value = 1

Table S50. Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	10	0.1 - 177.0 (6.0)
subtype1	22	5	0.1 - 177.0 (10.6)
subtype2	17	4	0.6 - 101.8 (5.5)
subtype3	8	1	0.7 - 53.1 (2.0)

Figure S43. Get High-res Image Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #1: 'Time to Death'

'MIRseq Mature CNMF subtypes' versus 'AGE'

P value = 0.181 (ANOVA), Q value = 1

Table S51. Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	48	47.8 (12.9)
subtype1	22	46.3 (13.8)
subtype2	18	52.0 (12.2)
subtype3	8	42.8 (10.2)

Figure S44. Get High-res Image Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #2: 'AGE'

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

P value = 0.921 (Fisher's exact test), Q value = 1

Table S52. Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients	NO	YES
ALL	16	32
subtype1	8	14
subtype2	6	12
subtype3	2	6

Figure S45. Get High-res Image Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'MIRseq Mature CNMF subtypes' versus 'NUMBERPACKYEARSSMOKED'

P value = 0.623 (ANOVA), Q value = 1

Table S53. Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

	nPatients	Mean (Std.Dev)
ALL	14	20.6 (13.1)
subtype1	6	21.0 (15.8)
subtype2	4	15.5 (6.7)
subtype3	4	25.0 (14.7)

Figure S46. Get High-res Image Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

'MIRseq Mature CNMF subtypes' versus 'DISTANT.METASTASIS'

P value = 0.212 (Fisher's exact test), Q value = 1

Table S54. Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	MX
ALL	29	14
subtype1	15	4
subtype2	11	6
subtype3	3	4

Figure S47. Get High-res Image Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'MIRseq Mature CNMF subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 0.78 (Fisher's exact test), Q value = 1

Table S55. Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1
ALL	27	17
subtype1	11	8
subtype2	10	7
subtype3	6	2

Figure S48. Get High-res Image Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'MIRseq Mature CNMF subtypes' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.705 (ANOVA), Q value = 1

Table S56. Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	42	1.1 (2.8)
subtype1	18	1.3 (3.7)
subtype2	17	1.2 (2.2)
subtype3	7	0.3 (0.5)

Figure S49. Get High-res Image Clustering Approach #7: 'MIRseq Mature CNMF subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

Clustering Approach #8: 'MIRseq Mature cHierClus subtypes'

Table S57. Get Full Table Description of clustering approach #8: 'MIRseq Mature cHierClus subtypes'

Cluster Labels	1	2	3
Number of samples	5	18	25

'MIRseq Mature cHierClus subtypes' versus 'Time to Death'

P value = 0.52 (logrank test), Q value = 1

Table S58. Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	47	10	0.1 - 177.0 (6.0)
subtype1	5	1	0.7 - 35.6 (2.2)
subtype2	17	2	0.1 - 95.1 (5.5)
subtype3	25	7	0.3 - 177.0 (21.7)

Figure S50. Get High-res Image Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #1: 'Time to Death'

'MIRseq Mature cHierClus subtypes' versus 'AGE'

P value = 0.186 (ANOVA), Q value = 1

Table S59. Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	48	47.8 (12.9)
subtype1	5	44.2 (11.0)
subtype2	18	44.3 (10.2)
subtype3	25	51.1 (14.4)

Figure S51. Get High-res Image Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #2: 'AGE'

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

P value = 0.911 (Fisher's exact test), Q value = 1

Table S60. Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

nPatients	NO	YES
ALL	16	32
subtype1	1	4
subtype2	6	12
subtype3	9	16

Figure S52. Get High-res Image Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #3: 'RADIATIONS.RADIATION.REGIMENINDICATION'

'MIRseq Mature cHierClus subtypes' versus 'NUMBERPACKYEARSSMOKED'

P value = 0.27 (ANOVA), Q value = 1

Table S61. Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

	nPatients	Mean (Std.Dev)
ALL	14	20.6 (13.1)
subtype1	2	37.5 (3.5)
subtype2	6	21.8 (15.9)
subtype3	6	13.7 (3.8)

Figure S53. Get High-res Image Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #4: 'NUMBERPACKYEARSSMOKED'

'MIRseq Mature cHierClus subtypes' versus 'DISTANT.METASTASIS'

P value = 0.416 (Fisher's exact test), Q value = 1

Table S62. Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

nPatients	M0	MX
ALL	29	14
subtype1	2	3
subtype2	10	4
subtype3	17	7

Figure S54. Get High-res Image Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #5: 'DISTANT.METASTASIS'

'MIRseq Mature cHierClus subtypes' versus 'LYMPH.NODE.METASTASIS'

P value = 0.905 (Fisher's exact test), Q value = 1

Table S63. Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients	N0	N1
ALL	27	17
subtype1	3	2
subtype2	10	5
subtype3	14	10

Figure S55. Get High-res Image Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'MIRseq Mature cHierClus subtypes' versus 'NUMBER.OF.LYMPH.NODES'

P value = 0.436 (ANOVA), Q value = 1

Table S64. Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

	nPatients	Mean (Std.Dev)
ALL	42	1.1 (2.8)
subtype1	4	0.5 (0.6)
subtype2	15	0.5 (0.7)
subtype3	23	1.6 (3.7)

Figure S56. Get High-res Image Clustering Approach #8: 'MIRseq Mature cHierClus subtypes' versus Clinical Feature #7: 'NUMBER.OF.LYMPH.NODES'

Methods & Data

Input

Cluster data file = CESC-TP.mergedcluster.txt
Clinical data file = CESC-TP.clin.merged.picked.txt
Number of patients = 48
Number of clustering approaches = 8
Number of selected clinical features = 8
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

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between two tumor subtypes using 't.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

Download Results

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)

[2] Monti et al., Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data, Machine Learning 52(1):91-118 (2003)

[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)

[6] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)

[7] 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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