Table 2.
Characterization of pan-cancer clusters of tumors after removing tissue effects.
| Clusters | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical information | Cancer type# | bc | c | d | ab | ab | ab | bc | a | |||
| Metastasis (%) | 5c | 4de | 3e | 17ab | 5de | 7 cd | 12bc | 21a | ||||
| Survival time (years)* | 2.2a | 2.1a | 2.8b | 1.8a | 1.5ab | 1.8ab | 2.2ab | 2.0a | ||||
| Stage (overall staging via TNM system17) | IVab | IVbc | IIIc | IVab | IIIabc | IIIab | IIIabc | IVab | ||||
| Tumor-free fraction (%) | 60a | 70a | 80b | 60a | 60a | 60a | 60a | 60a | ||||
| Intratumor heterogenity (%) | 13ab | 14ab | 4d | 10c | 15a | 12abc | 14ab | 9bc | ||||
| Proliferation rate (norm. diff. between dividing and non-dividing cells) | 0.4a | 0.3a | −0.4b | 0.3a | 0.3a | 0.4a | 0.4a | 0.5a | ||||
| Demographic information | Age (years) | 61a | 62a | 57b | 60ab | 60ab | 61ab | 62a | 57b | |||
| Sex (% of females) | 52ab | 54a | 50ab | 50ab | 53ab | 46b | 58a | 41b | ||||
| Genome instability rates (as deviations from normal genome) | Non-silent mutation | 1.8bc | 2.2bc | 0.7d | 3.2a | 2.0abc | 1.7c | 2.5ab | 1.8bc | |||
| Aneuploidy | 12a | 12a | 3b | 10a | 14a | 11a | 12a | 10a | ||||
| Homologous recombination defects | 22ab | 16c | 8d | 23ab | 22abc | 25a | 27a | 19bc | ||||
| Immune infiltration (as deviations from leukocytes fraction) | Th1 CD4 + cells (x102) | −5.9b | −5.7b | −3.1a | −6.6b | −8.0b | −6.7b | −5.6b | −5.8b | |||
| Th2 CD4 + cells (x102) | 2.6c | 2.3c | 1.6c | 4.2ab | 5.1abc | 5.4ab | 5.2ab | 6.1a | ||||
| Th17 CD4 + cells (x102) | −8.8b | −7.5b | 5.4a | −14.7c | −5.4b | −4.5b | −8.5b | −9.0b | ||||
| Activated natural killer cells (x10−2) | 2bc | 0.2bc | 0.3a | 0.3ab | 0.2bc | 0.1c | 0.2bc | 0.2bc | ||||
| Lymphocytes (x10−2) | 4.7bc | 5.9b | 4.1a | 4.4bc | 4.6bc | 3.1bc | 4.9bc | 3.0c | ||||
| Tumor-infiltrating lymphocytes | 1.7b | 1.7b | 1.9a | 1.7b | 1.8ab | 1.6b | 1.8b | 1.6b | ||||
| Functional Classes (such as pathways and ontologies) ** | DNA replication&¶,(1) | −0.6d | 0.6a | −0.1bc | 0.6a | 0.4ab | 0.7a | −0.3c | −0.2bc | |||
| Mythochondrial translation&¶,(2) | 0.4d | −0.3b | 0.0c | −0.9a | 0.3 cd | −1.1a | 1.9e | 0.5d | ||||
| mir-has-615b targets▯,(3) | −1.1c | 0.7a | −0.1b | 0.7a | −0.2b | 0.8a | −1.1c | −0.1b | ||||
| S phase and DNA synthesis¶,(4) | −1.5 f | 1.0b | −0.1d | 0.5c | 0.3c | 1.3a | −0.4e | −0.4e | ||||
| #Cluster composition in cancer types (%). | ||||||||||||
| C1 | COAD (14.2), LUAD (11.7), BRCA (10.7), SKCM (8.1), SARC (7.1), READ (6.4), PRAD (4.8), ESCA (4.6), CESC (4.1), LUSC (4.1), STAD (4.1), BLCA (3.8), PAAD (3.6), TGCT (2.5), ACC (2.3), MESO (2), LIHC (1.5), UCEC (1.5), PCPG (1), HNSC (0.8), KIRC (0.3), LGG (0.3), OV (0.3), and UVM (0.3). | |||||||||||
| C2 | BRCA (11.1), COAD (11.1), STAD (9.6), LUSC (7.4), LUAD (7.1), SKCM (6.1), CESC (5.6), BLCA (5.4), SARC (5.4), READ (4), ESCA (3.1), KIRP (2.5), PAAD (2.5), PRAD (2.5), PCPG (2.2), HNSC (1.7), LIHC (1.5), UVM (1.5), MESO (1.4), UCEC (1.4), ACC (1.3), KIRC (1.1), GBM (1), THYM (1), LGG (0.8), THCA (0.7), TGCT (0.6), DLBC (0.1), and LAML (0.1). | |||||||||||
| C3 | THCA (16.1), PRAD (13.2), BRCA (9.3), LUAD (6.3), SKCM (4.4), BLCA (4.3), LUSC (3.9), STAD (3.8), COAD (3.4), TGCT (3.4), UCEC (3.4), PAAD (3.3), CESC (3.2), THYM (3.2), PCPG (3.1), LGG (2.5), SARC (1.7), UVM (1.6), HNSC (1.3), LIHC (1.2), KIRC (1.1), MESO (1.1), ESCA (1), GBM (1), LAML (0.9), DLBC (0.7), READ (0.5), KIRP (0.4), CHOL (0.4), UCS (0.1), ACC (0.1), and OV (0.1). | |||||||||||
| C4 | SKCM (21.7), BLCA (13), CESC (9.6), LUAD (9.6), LUSC (8.7), BRCA (7.8), ESCA (4.3), UVM (4.3), MESO (3.5), HNSC (2.6), SARC (2.6), GBM (1.7), LIHC (1.7), STAD (1.7), UCEC (1.7), COAD (0.9), KIRP (0.9), PRAD (0.9), READ (0.9), TGCT (0.9), and THYM (0.9). | |||||||||||
| C5 | BLCA (18.4), LUAD (15.8), CESC (10.5), SKCM (10.5), PRAD (7.9), BRCA (5.3), ESCA (5.3), STAD (5.3), COAD (2.6), GBM (2.6), HNSC (2.6), LIHC (2.6), LUSC (2.6), PAAD (2.6), PCPG (2.6), and TGCT (2.6). | |||||||||||
| C6 | BRCA (31.5), LUSC (9.7), ESCA (8.6), SKCM (8.6), BLCA (8.2), STAD (6.5), LUAD (5.7), PRAD (5.7), HNSC (3.9), CESC (2.5), SARC (2.2), PAAD (1.8), GBM (0.7), LGG (0.7), UCEC (0.7), UVM (0.7), CHOL (0.4), DLBC (0.4), MESO (0.4), PCPG (0.4), READ (0.4), and TGCT (0.4). | |||||||||||
| C7 | SKCM (14.7), BRCA (11.5), LUSC (11), ESCA (8.4), STAD (7.3), SARC (6.8), CESC (5.8), LUAD (5.8), UVM (4.7), BLCA (4.2), PAAD (3.1), HNSC (2.6), COAD (2.1), PRAD (2.1), LIHC (1.6), MESO (1.6), READ (1.6), UCEC (1.6), TGCT (1), DLBC (0.5), GBM (0.5), LGG (0.5), OV (0.5), and THCA (0.5). | |||||||||||
| C8 | SKCM (24.8), BRCA (23.9), CESC (12.8), PCPG (6.8), BLCA (5.1), SARC (5.1), LUSC (4.3), HNSC (3.4), UCEC (2.6), COAD (1.7), ESCA (1.7), MESO (1.7), READ (1.7), TGCT (1.7), LUAD (0.9), OV (0.9), and UVM (0.9). | |||||||||||
The clusters produced by integration of whole-genome profiles of gene expression (GE), copy number variants (CNV), and DNA methylation (METH) were characterized in terms of clinical, demographic, immune and molecular information. The table shows those variables with significant differences in at least one cluster. For each variable, different letters represent significant differences between clusters.
*Values represent median survival times by cluster. Letters represent significant differences under the log-rank test to compare the entire survival curves of each cluster.
**Databases: GO Biological process (&), miRTabrBase (▯), Reactome (¶). Functional classes significant at FDR adj. p-value < 0.05.
Overlap between our selected group of genes and databases:
(1)GINS1, POLD3, PRIM2, POLD4, PCNA, MCM8 and MCM3.
(2)MRPS26, MRPL2, MRPL51, MRPS35, MRPL16, MRPS18A, MRPS10, MRPL14, MRPL48, MRPL21 and MRPL11.
(3)PANK2, SF3B2, PCNA, HSP90AB1, NOP2, ATN1, CHD4, HOXC13, PRICKLE4, DPP3, C12ORF57, LDHB, CCND3, CCND2, STK35, RAB23, PPP6R3, IDH3B, RPS3, SIRPA, PSMF1, DNM1L, NKX2-5, PRNP, UVRAG, PPIL1, TPI1, DST, CSNK2A1, SMOX, YIPF3, DDX11, ENTPD6, MAD2L1BP, PPP2R5D, MUT, FBXL14, MRPL21, KLHL42, WNK1, RPL7L1, NCAPD2, FKBP4 and GAPDH.
(4)GINS1, POLD3, PRIM2, POLD4, PCNA, CDKN1B, CCND1, MCM8, MCM3, PSMF1 and CDC25B.