This pipeline computes the correlation between cancer subtypes identified by different molecular patterns and selected clinical features.
Testing the association between subtypes identified by 10 different clustering approaches and 5 clinical features across 866 patients, 16 significant findings detected with P value < 0.05.
-
CNMF clustering analysis on array-based mRNA expression data identified 8 subtypes that correlate to 'Time to Death' and 'AGE'.
-
Consensus hierarchical clustering analysis on array-based mRNA expression data identified 3 subtypes that correlate to 'AGE'.
-
5 subtypes identified in current cancer cohort by 'CN CNMF'. These subtypes correlate to 'Time to Death' and 'GENDER'.
-
6 subtypes identified in current cancer cohort by 'METHLYATION CNMF'. These subtypes correlate to 'Time to Death' and 'AGE'.
-
CNMF clustering analysis on RPPA data identified 3 subtypes that correlate to 'Time to Death' and 'AGE'.
-
Consensus hierarchical clustering analysis on RPPA data identified 3 subtypes that correlate to 'AGE'.
-
CNMF clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that correlate to 'AGE'.
-
Consensus hierarchical clustering analysis on sequencing-based mRNA expression data identified 3 subtypes that correlate to 'Time to Death' and 'AGE'.
-
CNMF clustering analysis on sequencing-based miR expression data identified 3 subtypes that correlate to 'Time to Death' and 'AGE'.
-
Consensus hierarchical clustering analysis on sequencing-based miR expression data identified 3 subtypes that correlate to '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 | 0.00106 | 2.3e-06 | 0.0519 | 0.897 | 0.391 |
mRNA cHierClus subtypes | 0.557 | 0.00176 | 0.322 | 0.195 | 0.335 |
CN CNMF | 0.0167 | 0.101 | 0.000906 | 0.355 | 0.737 |
METHLYATION CNMF | 0.0348 | 0.000404 | 0.0531 | 0.23 | 0.7 |
RPPA CNMF subtypes | 0.0124 | 0.0191 | 0.058 | 0.944 | 0.0593 |
RPPA cHierClus subtypes | 0.0901 | 0.000121 | 0.187 | 0.726 | 0.307 |
RNAseq CNMF subtypes | 0.179 | 0.00573 | 0.0991 | 0.467 | 0.184 |
RNAseq cHierClus subtypes | 0.00841 | 0.000672 | 0.0886 | 0.255 | 0.0533 |
MIRseq CNMF subtypes | 0.00145 | 0.0286 | 0.683 | 0.424 | 0.587 |
MIRseq cHierClus subtypes | 0.0666 | 0.00927 | 0.359 | 0.687 | 0.919 |
Cluster Labels | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
---|---|---|---|---|---|---|---|---|
Number of samples | 126 | 41 | 21 | 103 | 107 | 73 | 20 | 38 |
P value = 0.00106 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 497 | 65 | 0.1 - 223.4 (24.1) |
subtype1 | 116 | 17 | 0.1 - 177.4 (24.4) |
subtype2 | 40 | 4 | 0.1 - 157.4 (40.6) |
subtype3 | 19 | 3 | 0.3 - 223.4 (14.0) |
subtype4 | 98 | 12 | 0.1 - 211.5 (21.9) |
subtype5 | 104 | 10 | 0.3 - 220.9 (19.0) |
subtype6 | 64 | 14 | 0.1 - 189.0 (24.9) |
subtype7 | 19 | 2 | 0.2 - 97.5 (36.3) |
subtype8 | 37 | 3 | 0.3 - 82.7 (20.0) |
P value = 2.3e-06 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 529 | 57.9 (13.2) |
subtype1 | 126 | 58.5 (14.3) |
subtype2 | 41 | 50.0 (12.1) |
subtype3 | 21 | 59.4 (13.8) |
subtype4 | 103 | 53.8 (12.6) |
subtype5 | 107 | 62.1 (12.4) |
subtype6 | 73 | 58.5 (12.5) |
subtype7 | 20 | 60.4 (9.9) |
subtype8 | 38 | 60.3 (12.0) |
P value = 0.0519 (Chi-square test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 523 | 6 |
subtype1 | 122 | 4 |
subtype2 | 41 | 0 |
subtype3 | 20 | 1 |
subtype4 | 103 | 0 |
subtype5 | 107 | 0 |
subtype6 | 73 | 0 |
subtype7 | 19 | 1 |
subtype8 | 38 | 0 |
P value = 0.897 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 147 | 382 |
subtype1 | 33 | 93 |
subtype2 | 11 | 30 |
subtype3 | 4 | 17 |
subtype4 | 34 | 69 |
subtype5 | 29 | 78 |
subtype6 | 19 | 54 |
subtype7 | 5 | 15 |
subtype8 | 12 | 26 |
P value = 0.391 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 221 | 308 |
subtype1 | 53 | 73 |
subtype2 | 20 | 21 |
subtype3 | 5 | 16 |
subtype4 | 48 | 55 |
subtype5 | 45 | 62 |
subtype6 | 26 | 47 |
subtype7 | 6 | 14 |
subtype8 | 18 | 20 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 129 | 129 | 271 |
P value = 0.557 (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 | 125 | 14 | 0.3 - 157.4 (27.2) |
subtype3 | 254 | 36 | 0.1 - 223.4 (23.1) |
P value = 0.00176 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 529 | 57.9 (13.2) |
subtype1 | 129 | 55.1 (12.6) |
subtype2 | 129 | 56.7 (13.1) |
subtype3 | 271 | 59.8 (13.4) |
P value = 0.322 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 523 | 6 |
subtype1 | 129 | 0 |
subtype2 | 128 | 1 |
subtype3 | 266 | 5 |
P value = 0.195 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 147 | 382 |
subtype1 | 43 | 86 |
subtype2 | 37 | 92 |
subtype3 | 67 | 204 |
P value = 0.335 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 221 | 308 |
subtype1 | 59 | 70 |
subtype2 | 57 | 72 |
subtype3 | 105 | 166 |
Cluster Labels | 1 | 2 | 3 | 4 | 5 |
---|---|---|---|---|---|
Number of samples | 324 | 231 | 61 | 186 | 41 |
P value = 0.0167 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 785 | 94 | 0.0 - 223.4 (18.4) |
subtype1 | 302 | 31 | 0.0 - 223.4 (20.3) |
subtype2 | 212 | 25 | 0.1 - 162.0 (16.8) |
subtype3 | 59 | 5 | 0.0 - 189.0 (18.9) |
subtype4 | 173 | 25 | 0.0 - 211.5 (18.0) |
subtype5 | 39 | 8 | 0.7 - 220.9 (21.5) |
P value = 0.101 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 842 | 58.5 (13.2) |
subtype1 | 323 | 58.3 (13.0) |
subtype2 | 231 | 58.5 (14.2) |
subtype3 | 61 | 61.6 (11.5) |
subtype4 | 186 | 57.2 (13.0) |
subtype5 | 41 | 61.8 (12.4) |
P value = 0.000906 (Chi-square test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 834 | 9 |
subtype1 | 324 | 0 |
subtype2 | 223 | 8 |
subtype3 | 60 | 1 |
subtype4 | 186 | 0 |
subtype5 | 41 | 0 |
P value = 0.355 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 197 | 646 |
subtype1 | 67 | 257 |
subtype2 | 52 | 179 |
subtype3 | 14 | 47 |
subtype4 | 52 | 134 |
subtype5 | 12 | 29 |
P value = 0.737 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 301 | 542 |
subtype1 | 119 | 205 |
subtype2 | 75 | 156 |
subtype3 | 21 | 40 |
subtype4 | 69 | 117 |
subtype5 | 17 | 24 |
Cluster Labels | 1 | 2 | 3 | 4 | 5 | 6 |
---|---|---|---|---|---|---|
Number of samples | 92 | 134 | 88 | 123 | 33 | 83 |
P value = 0.0348 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 524 | 62 | 0.0 - 223.4 (18.0) |
subtype1 | 87 | 14 | 0.2 - 211.5 (20.0) |
subtype2 | 126 | 10 | 0.2 - 223.4 (13.6) |
subtype3 | 86 | 13 | 0.0 - 173.0 (16.1) |
subtype4 | 116 | 13 | 0.1 - 194.3 (20.0) |
subtype5 | 32 | 4 | 0.1 - 157.4 (16.1) |
subtype6 | 77 | 8 | 0.0 - 130.2 (25.8) |
P value = 0.000404 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 552 | 57.8 (13.1) |
subtype1 | 92 | 56.4 (13.1) |
subtype2 | 134 | 58.6 (12.5) |
subtype3 | 88 | 63.2 (11.6) |
subtype4 | 123 | 55.6 (14.4) |
subtype5 | 33 | 54.9 (13.6) |
subtype6 | 82 | 56.6 (11.8) |
P value = 0.0531 (Chi-square test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 547 | 6 |
subtype1 | 92 | 0 |
subtype2 | 133 | 1 |
subtype3 | 86 | 2 |
subtype4 | 122 | 1 |
subtype5 | 31 | 2 |
subtype6 | 83 | 0 |
P value = 0.23 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 136 | 417 |
subtype1 | 28 | 64 |
subtype2 | 31 | 103 |
subtype3 | 19 | 69 |
subtype4 | 36 | 87 |
subtype5 | 4 | 29 |
subtype6 | 18 | 65 |
P value = 0.7 (Chi-square test)
nPatients | NO | YES |
---|---|---|
ALL | 204 | 349 |
subtype1 | 33 | 59 |
subtype2 | 52 | 82 |
subtype3 | 33 | 55 |
subtype4 | 50 | 73 |
subtype5 | 9 | 24 |
subtype6 | 27 | 56 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 151 | 134 | 123 |
P value = 0.0124 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 380 | 44 | 0.1 - 189.0 (24.5) |
subtype1 | 135 | 22 | 0.1 - 186.4 (24.3) |
subtype2 | 130 | 11 | 0.2 - 146.5 (17.4) |
subtype3 | 115 | 11 | 0.3 - 189.0 (28.5) |
P value = 0.0191 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 408 | 57.9 (13.1) |
subtype1 | 151 | 56.3 (13.1) |
subtype2 | 134 | 60.4 (13.8) |
subtype3 | 123 | 57.0 (11.9) |
P value = 0.058 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 403 | 5 |
subtype1 | 151 | 0 |
subtype2 | 130 | 4 |
subtype3 | 122 | 1 |
P value = 0.944 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 124 | 284 |
subtype1 | 46 | 105 |
subtype2 | 42 | 92 |
subtype3 | 36 | 87 |
P value = 0.0593 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 188 | 220 |
subtype1 | 64 | 87 |
subtype2 | 73 | 61 |
subtype3 | 51 | 72 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 135 | 162 | 111 |
P value = 0.0901 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 380 | 44 | 0.1 - 189.0 (24.5) |
subtype1 | 120 | 18 | 0.1 - 189.0 (23.5) |
subtype2 | 151 | 17 | 0.2 - 129.7 (19.9) |
subtype3 | 109 | 9 | 0.2 - 173.0 (25.3) |
P value = 0.000121 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 408 | 57.9 (13.1) |
subtype1 | 135 | 54.3 (13.0) |
subtype2 | 162 | 60.7 (13.4) |
subtype3 | 111 | 58.0 (11.7) |
P value = 0.187 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 403 | 5 |
subtype1 | 135 | 0 |
subtype2 | 158 | 4 |
subtype3 | 110 | 1 |
P value = 0.726 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 124 | 284 |
subtype1 | 40 | 95 |
subtype2 | 47 | 115 |
subtype3 | 37 | 74 |
P value = 0.307 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 188 | 220 |
subtype1 | 55 | 80 |
subtype2 | 80 | 82 |
subtype3 | 53 | 58 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 234 | 147 | 422 |
P value = 0.179 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 748 | 92 | 0.0 - 223.4 (19.0) |
subtype1 | 215 | 32 | 0.0 - 211.5 (19.2) |
subtype2 | 142 | 13 | 0.3 - 194.3 (28.6) |
subtype3 | 391 | 47 | 0.0 - 223.4 (17.0) |
P value = 0.00573 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 802 | 58.0 (13.1) |
subtype1 | 234 | 57.0 (12.8) |
subtype2 | 146 | 55.7 (12.3) |
subtype3 | 422 | 59.3 (13.5) |
P value = 0.0991 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 795 | 8 |
subtype1 | 234 | 0 |
subtype2 | 146 | 1 |
subtype3 | 415 | 7 |
P value = 0.467 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 191 | 612 |
subtype1 | 57 | 177 |
subtype2 | 40 | 107 |
subtype3 | 94 | 328 |
P value = 0.184 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 298 | 505 |
subtype1 | 86 | 148 |
subtype2 | 64 | 83 |
subtype3 | 148 | 274 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 235 | 376 | 192 |
P value = 0.00841 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 748 | 92 | 0.0 - 223.4 (19.0) |
subtype1 | 229 | 19 | 0.1 - 194.3 (25.4) |
subtype2 | 343 | 47 | 0.0 - 223.4 (17.0) |
subtype3 | 176 | 26 | 0.0 - 211.5 (19.1) |
P value = 0.000672 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 802 | 58.0 (13.1) |
subtype1 | 234 | 56.2 (12.2) |
subtype2 | 376 | 59.9 (13.6) |
subtype3 | 192 | 56.4 (12.8) |
P value = 0.0886 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 795 | 8 |
subtype1 | 234 | 1 |
subtype2 | 369 | 7 |
subtype3 | 192 | 0 |
P value = 0.255 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 191 | 612 |
subtype1 | 59 | 176 |
subtype2 | 80 | 296 |
subtype3 | 52 | 140 |
P value = 0.0533 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 298 | 505 |
subtype1 | 101 | 134 |
subtype2 | 125 | 251 |
subtype3 | 72 | 120 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 185 | 411 | 242 |
P value = 0.00145 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 779 | 95 | 0.0 - 223.4 (18.9) |
subtype1 | 178 | 19 | 0.4 - 159.1 (21.0) |
subtype2 | 381 | 37 | 0.0 - 223.4 (17.9) |
subtype3 | 220 | 39 | 0.0 - 211.5 (19.2) |
P value = 0.0286 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 837 | 58.4 (13.3) |
subtype1 | 184 | 57.3 (12.7) |
subtype2 | 411 | 59.7 (13.7) |
subtype3 | 242 | 57.1 (12.8) |
P value = 0.683 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 829 | 9 |
subtype1 | 184 | 1 |
subtype2 | 405 | 6 |
subtype3 | 240 | 2 |
P value = 0.424 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 193 | 645 |
subtype1 | 37 | 148 |
subtype2 | 102 | 309 |
subtype3 | 54 | 188 |
P value = 0.587 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 303 | 535 |
subtype1 | 68 | 117 |
subtype2 | 154 | 257 |
subtype3 | 81 | 161 |
Cluster Labels | 1 | 2 | 3 |
---|---|---|---|
Number of samples | 205 | 268 | 365 |
P value = 0.0666 (logrank test)
nPatients | nDeath | Duration Range (Median), Month | |
---|---|---|---|
ALL | 779 | 95 | 0.0 - 223.4 (18.9) |
subtype1 | 192 | 30 | 0.0 - 211.5 (19.7) |
subtype2 | 237 | 31 | 0.1 - 223.4 (17.8) |
subtype3 | 350 | 34 | 0.0 - 177.4 (18.6) |
P value = 0.00927 (ANOVA)
nPatients | Mean (Std.Dev) | |
---|---|---|
ALL | 837 | 58.4 (13.3) |
subtype1 | 205 | 56.9 (12.7) |
subtype2 | 268 | 60.4 (14.3) |
subtype3 | 364 | 57.8 (12.7) |
P value = 0.359 (Fisher's exact test)
nPatients | FEMALE | MALE |
---|---|---|
ALL | 829 | 9 |
subtype1 | 204 | 1 |
subtype2 | 263 | 5 |
subtype3 | 362 | 3 |
P value = 0.687 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 193 | 645 |
subtype1 | 49 | 156 |
subtype2 | 65 | 203 |
subtype3 | 79 | 286 |
P value = 0.919 (Fisher's exact test)
nPatients | NO | YES |
---|---|---|
ALL | 303 | 535 |
subtype1 | 73 | 132 |
subtype2 | 95 | 173 |
subtype3 | 135 | 230 |
-
Cluster data file = BRCA.mergedcluster.txt
-
Clinical data file = BRCA.clin.merged.picked.txt
-
Number of patients = 866
-
Number of clustering approaches = 10
-
Number of selected clinical features = 5
-
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.