This pipeline computes the correlation between cancer subtypes identified by different molecular patterns and selected clinical features.
Testing the association between subtypes identified by 7 different clustering approaches and 5 clinical features across 851 patients, 13 significant findings detected with P value < 0.05.
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CNMF clustering analysis on array-based mRNA expression data identified 8 subtypes that correlate to 'Time to Death', 'AGE', and 'GENDER'.
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Consensus hierarchical clustering analysis on array-based mRNA expression data identified 3 subtypes that correlate to 'AGE'.
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7 subtypes identified in current cancer cohort by 'METHLYATION CNMF'. These subtypes correlate to 'Time to Death', 'AGE', and 'GENDER'.
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CNMF clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that correlate to 'AGE'.
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Consensus hierarchical clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that correlate to 'NEOADJUVANT.THERAPY'.
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CNMF clustering analysis on sequencing-based miR expression data identified 3 subtypes that correlate to 'Time to Death' and 'AGE'.
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Consensus hierarchical clustering analysis on sequencing-based miR expression data identified 3 subtypes that correlate to 'Time to Death' and 'AGE'.
Clinical Features |
Time to Death |
AGE | GENDER |
RADIATIONS RADIATION REGIMENINDICATION |
NEOADJUVANT THERAPY |
Statistical Tests | logrank test | ANOVA | Fisher's exact test | Fisher's exact test | Fisher's exact test |
mRNA CNMF subtypes | 7.48e-05 | 5.88e-06 | 0.0354 | 0.848 | 0.398 |
mRNA cHierClus subtypes | 0.445 | 0.00183 | 0.323 | 0.224 | 0.38 |
METHLYATION CNMF | 0.000294 | 0.00115 | 0.0202 | 0.13 | 0.988 |
RNAseq CNMF subtypes | 0.137 | 0.0386 | 0.148 | 0.388 | 0.0981 |
RNAseq cHierClus subtypes | 0.187 | 0.118 | 0.158 | 0.142 | 0.00648 |
MIRseq CNMF subtypes | 0.00773 | 0.00868 | 0.222 | 0.685 | 0.281 |
MIRseq cHierClus subtypes | 0.0258 | 0.0131 | 0.13 | 0.412 | 0.282 |
Cluster Labels | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
---|---|---|---|---|---|---|---|---|
Number of samples | 20 | 34 | 117 | 103 | 120 | 73 | 20 | 42 |
P value = 7.48e-05 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 497 | 65 | 0.1 - 223.4 (24.1) |
subtype1 | 18 | 3 | 0.3 - 92.0 (14.2) |
subtype2 | 33 | 3 | 0.1 - 157.4 (43.4) |
subtype3 | 109 | 17 | 0.1 - 177.4 (25.1) |
subtype4 | 98 | 12 | 0.1 - 211.5 (21.9) |
subtype5 | 115 | 10 | 0.3 - 223.4 (19.0) |
subtype6 | 64 | 14 | 0.1 - 189.0 (24.6) |
subtype7 | 19 | 2 | 0.2 - 97.5 (36.3) |
subtype8 | 41 | 4 | 0.3 - 112.4 (20.0) |
P value = 5.88e-06 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 529 | 57.9 (13.2) |
subtype1 | 20 | 59.6 (14.1) |
subtype2 | 34 | 49.9 (10.1) |
subtype3 | 117 | 58.0 (14.3) |
subtype4 | 103 | 53.8 (12.6) |
subtype5 | 120 | 62.0 (12.7) |
subtype6 | 73 | 58.2 (12.7) |
subtype7 | 20 | 60.4 (9.9) |
subtype8 | 42 | 59.9 (12.8) |
P value = 0.0354 (Chi-square test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 523 | 6 |
subtype1 | 19 | 1 |
subtype2 | 34 | 0 |
subtype3 | 113 | 4 |
subtype4 | 103 | 0 |
subtype5 | 120 | 0 |
subtype6 | 73 | 0 |
subtype7 | 19 | 1 |
subtype8 | 42 | 0 |
P value = 0.848 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 382 | 147 |
subtype1 | 17 | 3 |
subtype2 | 25 | 9 |
subtype3 | 86 | 31 |
subtype4 | 69 | 34 |
subtype5 | 86 | 34 |
subtype6 | 54 | 19 |
subtype7 | 15 | 5 |
subtype8 | 30 | 12 |
P value = 0.398 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 307 | 222 |
subtype1 | 15 | 5 |
subtype2 | 17 | 17 |
subtype3 | 66 | 51 |
subtype4 | 55 | 48 |
subtype5 | 71 | 49 |
subtype6 | 47 | 26 |
subtype7 | 14 | 6 |
subtype8 | 22 | 20 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 129 | 136 | 264 |
P value = 0.445 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 497 | 65 | 0.1 - 223.4 (24.1) |
subtype1 | 118 | 15 | 0.1 - 211.5 (21.6) |
subtype2 | 134 | 15 | 0.3 - 157.4 (27.6) |
subtype3 | 245 | 35 | 0.1 - 223.4 (21.1) |
P value = 0.00183 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 529 | 57.9 (13.2) |
subtype1 | 129 | 55.1 (12.6) |
subtype2 | 136 | 56.8 (13.0) |
subtype3 | 264 | 59.8 (13.4) |
P value = 0.323 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 523 | 6 |
subtype1 | 129 | 0 |
subtype2 | 135 | 1 |
subtype3 | 259 | 5 |
P value = 0.224 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 382 | 147 |
subtype1 | 86 | 43 |
subtype2 | 98 | 38 |
subtype3 | 198 | 66 |
P value = 0.38 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 307 | 222 |
subtype1 | 70 | 59 |
subtype2 | 76 | 60 |
subtype3 | 161 | 103 |
Cluster Labels | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
---|---|---|---|---|---|---|---|
Number of samples | 82 | 137 | 54 | 97 | 29 | 52 | 87 |
P value = 0.000294 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 509 | 61 | 0.0 - 223.4 (17.9) |
subtype1 | 77 | 12 | 0.2 - 211.5 (19.2) |
subtype2 | 129 | 12 | 0.3 - 223.4 (12.8) |
subtype3 | 50 | 10 | 0.0 - 162.0 (14.0) |
subtype4 | 93 | 7 | 0.1 - 177.4 (23.1) |
subtype5 | 29 | 3 | 0.1 - 157.4 (20.8) |
subtype6 | 50 | 9 | 0.0 - 109.9 (17.9) |
subtype7 | 81 | 8 | 0.0 - 194.3 (27.9) |
P value = 0.00115 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 536 | 57.5 (13.1) |
subtype1 | 82 | 54.8 (11.9) |
subtype2 | 137 | 58.7 (12.1) |
subtype3 | 54 | 59.0 (12.3) |
subtype4 | 97 | 55.3 (15.0) |
subtype5 | 29 | 57.1 (15.8) |
subtype6 | 52 | 63.9 (11.5) |
subtype7 | 85 | 56.0 (12.4) |
P value = 0.0202 (Chi-square test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 532 | 6 |
subtype1 | 82 | 0 |
subtype2 | 136 | 1 |
subtype3 | 54 | 0 |
subtype4 | 96 | 1 |
subtype5 | 27 | 2 |
subtype6 | 50 | 2 |
subtype7 | 87 | 0 |
P value = 0.13 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 409 | 129 |
subtype1 | 54 | 28 |
subtype2 | 107 | 30 |
subtype3 | 37 | 17 |
subtype4 | 75 | 22 |
subtype5 | 25 | 4 |
subtype6 | 43 | 9 |
subtype7 | 68 | 19 |
P value = 0.988 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 336 | 202 |
subtype1 | 49 | 33 |
subtype2 | 84 | 53 |
subtype3 | 33 | 21 |
subtype4 | 62 | 35 |
subtype5 | 19 | 10 |
subtype6 | 32 | 20 |
subtype7 | 57 | 30 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 229 | 130 | 392 |
P value = 0.137 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 697 | 86 | 0.0 - 223.4 (18.1) |
subtype1 | 208 | 31 | 0.0 - 211.5 (18.4) |
subtype2 | 124 | 10 | 0.3 - 157.4 (26.3) |
subtype3 | 365 | 45 | 0.0 - 223.4 (17.0) |
P value = 0.0386 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 749 | 57.7 (13.3) |
subtype1 | 229 | 56.6 (12.9) |
subtype2 | 128 | 56.1 (12.5) |
subtype3 | 392 | 58.9 (13.6) |
P value = 0.148 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 744 | 7 |
subtype1 | 229 | 0 |
subtype2 | 129 | 1 |
subtype3 | 386 | 6 |
P value = 0.388 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 568 | 183 |
subtype1 | 170 | 59 |
subtype2 | 94 | 36 |
subtype3 | 304 | 88 |
P value = 0.0981 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 458 | 293 |
subtype1 | 139 | 90 |
subtype2 | 69 | 61 |
subtype3 | 250 | 142 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 195 | 380 | 176 |
P value = 0.187 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 697 | 86 | 0.0 - 223.4 (18.1) |
subtype1 | 179 | 26 | 0.0 - 211.5 (16.5) |
subtype2 | 348 | 44 | 0.0 - 223.4 (16.8) |
subtype3 | 170 | 16 | 0.1 - 157.4 (25.5) |
P value = 0.118 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 749 | 57.7 (13.3) |
subtype1 | 195 | 56.3 (13.0) |
subtype2 | 380 | 58.6 (13.6) |
subtype3 | 174 | 57.3 (12.8) |
P value = 0.158 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 744 | 7 |
subtype1 | 195 | 0 |
subtype2 | 374 | 6 |
subtype3 | 175 | 1 |
P value = 0.142 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 568 | 183 |
subtype1 | 142 | 53 |
subtype2 | 299 | 81 |
subtype3 | 127 | 49 |
P value = 0.00648 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 458 | 293 |
subtype1 | 117 | 78 |
subtype2 | 250 | 130 |
subtype3 | 91 | 85 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 194 | 403 | 210 |
P value = 0.00773 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 748 | 92 | 0.0 - 223.4 (19.0) |
subtype1 | 186 | 21 | 0.3 - 159.1 (24.5) |
subtype2 | 372 | 39 | 0.0 - 223.4 (18.0) |
subtype3 | 190 | 32 | 0.0 - 211.5 (17.6) |
P value = 0.00868 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 805 | 58.2 (13.3) |
subtype1 | 192 | 56.0 (12.6) |
subtype2 | 403 | 59.5 (13.6) |
subtype3 | 210 | 57.6 (12.9) |
P value = 0.222 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 798 | 9 |
subtype1 | 194 | 0 |
subtype2 | 396 | 7 |
subtype3 | 208 | 2 |
P value = 0.685 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 623 | 184 |
subtype1 | 154 | 40 |
subtype2 | 307 | 96 |
subtype3 | 162 | 48 |
P value = 0.281 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 508 | 299 |
subtype1 | 116 | 78 |
subtype2 | 251 | 152 |
subtype3 | 141 | 69 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 223 | 423 | 161 |
P value = 0.0258 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 748 | 92 | 0.0 - 223.4 (19.0) |
subtype1 | 194 | 26 | 0.0 - 194.3 (17.0) |
subtype2 | 401 | 40 | 0.1 - 223.4 (19.1) |
subtype3 | 153 | 26 | 0.1 - 211.5 (20.0) |
P value = 0.0131 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 805 | 58.2 (13.3) |
subtype1 | 223 | 59.4 (13.4) |
subtype2 | 421 | 58.5 (13.2) |
subtype3 | 161 | 55.5 (12.8) |
P value = 0.13 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 798 | 9 |
subtype1 | 218 | 5 |
subtype2 | 419 | 4 |
subtype3 | 161 | 0 |
P value = 0.412 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 623 | 184 |
subtype1 | 179 | 44 |
subtype2 | 323 | 100 |
subtype3 | 121 | 40 |
P value = 0.282 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 508 | 299 |
subtype1 | 150 | 73 |
subtype2 | 258 | 165 |
subtype3 | 100 | 61 |
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Cluster data file = BRCA.mergedcluster.txt
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Clinical data file = BRCA.clin.merged.picked.txt
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Number of patients = 851
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Number of clustering approaches = 7
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Number of selected clinical features = 5
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Exclude small clusters that include fewer than K patients, K = 3
consensus non-negative matrix factorization clustering approach (Brunet et al. 2004)
Resampling-based clustering method (Monti et al. 2003)
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
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
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
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
This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.