Background
Subtypes of TNBC
Treatment of TNBC
TNBC and Cisplatin
Approach
Methods
Gene sets
GS ID | # of Genes | Gene Set Name |
---|---|---|
GS125959 | 2386 | Cisplatin interacting with Homo sapiens associated genes (MeSH:D002945) in CTD |
GS257116 | 883 | GS257116: Cisplatin interacting with Mus musculus associated genes (MeSH:D002945) in CTD |
GS263765 | 616 | Cisplatin interacting with Rattus norvegicus associated genes (MeSH:D002945) in CTD |
GS357326 | 378 | Genes from CTD that interact with cisplatin and are conserved in human and mouse |
GS357330 | 219 | Genes from CTD that interact with cisplatin and are conserved in human and rat |
GS357329 | 150 | Genes from CTD that interact with cisplatin and are conserved in rat and mouse |
GS271882 | 96 | Genes from CTD that interact with cisplatin and are conserved in human, mouse and rat |
GS237976 | 319 | [MeSH] Cisplatin:D002945 |
GS271616 | 215 | Genes upregulated in the BL1 subtype of triple negative breast cancer |
GS271617 | 154 | Genes upregulated in the BL2 subtype of triple negative breast cancer |
GS271618 | 535 | Genes upregulated in the IM subtype of triple negative breast cancer |
GS271619 | 247 | Genes upregulated in the M subtype of triple negative breast cancer |
GS271621 | 805 | Genes upregulated in LAR subtype of triple negative breast cancer |
GS271724 | 829 | Genes upregulated in the MSL subtype of triple negative breast cancer |
GS271627 | 251 | Genes downregulated in the BL1 subtype of triple negative breast cancer |
GS271636 | 127 | Genes downregulated in the BL2 subtype of triple negative breast cancer |
GS271640 | 302 | Genes downregulated in the IM subtype of triple negative breast cancer |
GS271722 | 446 | Genes downregulated in the M subtype of triple negative breast cancer |
GS271729 | 382 | Genes downregulated in the LAR subtype of triple negative breast cancer |
GS271725 | 255 | Genes downregulated in the MSL subtype of triple negative breast cancer |
Gene set analysis
Gene function analysis
Results
Gene sets of differentially expressed genes in TNBC subtypes
Cisplatin-associated genes are enriched for processes that are consistent with the cytotoxic action and response to cisplatin
A subset of cisplatin-associated differentially-expressed genes provide a signature for the resistant subtypes
Gene Symbol | Gene Name | BL1 | BL2 | M | LAR | Resistant | Death |
---|---|---|---|---|---|---|---|
ABCC2
| ATP binding cassette subfamily C member 2 | UP | * | ||||
ADM
| adrenomedullin | UP | UP | * | |||
AKT1
| AKT serine/threonine kinase 1 | UP | * | * | |||
BCL2
| BCL2 apoptosis regulator | DOWN | * | ||||
BCL2L1
| BCL2 like 1 | UP | * | * | |||
CASP8
| caspase 8 | DOWN | UP | * | * | ||
CAV1
| caveolin 1 | UP | * | ||||
CLU
| clusterin | DOWN | UP | * | * | ||
FAS
| Fas cell surface death receptor | DOWN | * | * | |||
FOS
| Fos proto-oncogene, AP-1 transcription factor subunit | DOWN | * | ||||
GSR
| glutathione-disulfide reductase | UP | * | ||||
GJA1
| gap junction protein alpha 1 | DOWN | UP | UP | * | ||
HSPB1
| heat shock protein family B (small) member 1 | UP | UP | * | |||
MSH2
| mutS homolog 2 | UP | DOWN | * | * | ||
NOX4
| NADPH oxidase 4 | DOWN | UP | * | * | ||
NQO1
| NAD(P)H quinone dehydrogenase 1 | UP | * | * | |||
PTK2
| protein tyrosine kinase 2 | UP | * | ||||
TUBA1A
| tubulin alpha 1a | UP | DOWN | * | |||
VCAM1
| vascular cell adhesion molecule 1 | DOWN | * | ||||
VIM
| vimentin | UP | DOWN | * |
Genes that are differentially regulated in cisplatin-resistant TNBC subtypes identify a variety of mechanisms to escape cisplatin toxicity
Gene Symbol | Evidence for Resistance | Reference |
---|---|---|
ABCC2 (up in LAR)
| A transporter that when overexpressed results in cisplatin resistance | [42] |
AKT1 (up in LAR)
| A stress-response protein that when amplified or overexpressed is correlated with cisplatin resistance | |
BCL2L1 (up in LAR)
| Apoptosis-inhibitor, overexpression correlates with cisplatin resistance | |
CASP8 (up in LAR down in M)
| Required for cisplatin-associated apoptosis | |
CLU (up in LAR)
| Well known to contribute to chemoresistance including cisplatin | |
FAS (down in M) | Overexpression induces cisplatin sensitivity and reduced expression correlates with resistance | |
GSR (up in LAR)
| Involved in the detoxification of cisplatin | |
MSH2 (down in LAR)
| Required for cisplatin induced apoptosis | |
NOX4 (up in M)
| Increased expression leads to more severe cisplatin toxicity | [37] |
NQO1 (up in LAR)
| A redox enzyme that has been show to contribute to resistance to cisplatin toxicity | |
TUBA1A (up in M down in LAR)
| Correlated with cisplatin-reistance in esophageal cells | [62] |
VCAM1 (down in M)
| Associated with epithelial to mesenchymal transition overexpression contributes to cisplatin resistance | [63] |
VIM (up in M down in LAR)
| Associated with epithelial to mesenchymal transition |