Table 1.
Summary of CTAs in TNBC.
| CTAs | Cellular Function | Institute | Cohort | Prevalence of CTAs in TNBC | Type of Assay | Antibodies | Role in TNBC | Ref. |
|---|---|---|---|---|---|---|---|---|
| CTAs associated with worse prognosis in TNBC | ||||||||
| A-kinase anchoring proteins (AKAP3) | Sperm function | Breast Cancer Research Centre (Tehran, Iran) [30] |
Asian | 20% (n = 25) |
Real-Time Polymerase Chain Reaction (RT-PCR) | Loss of expression in TNBC. Breast cancer patients who were positive for AKAP3 had better 5-year disease-free survival. | [30,31] | |
| Melanoma antigen gene (MAGE) | Not known. May promote tumourigenesis and metastasis. | Italian National Cancer Institute [32] | Caucasian | MAGE-A: 23% (n = 44) |
IHC | MAGE-A Antibody (6C1) | Frequently overexpressed in TNBC. Higher expression of MAGE-A was reported to define a very aggressive subtype of TNBC and correlated with poor prognosis of patients. MAGE-A3, -A6 and -C2 expression in breast cancers was significantly associated with negative ER or negative PR status, higher-grade tumours and correlated with worse outcomes. MAGE-A10 expression was associated with ER-negative, PR-negative and HER2-negative status. | [32,33,34,35,36,37,38,39,40,41,42,43] |
| Royal Brisbane Women’s Hospital [40] | Caucasian | MAGE-A: 47% (n = 65) |
IHC | MAGE-A Antibody (6C1), Santa Cruz Biotechnology(USA) | ||||
| Affiliated Tumour Hospital of Xinjiang Medical University [41] | Asian | MAGE-C: 38.2% (n = 110) |
IHC | Rabbit polyclonal MAGE-C2 Antibody, Sigma-Aldrich (USA) | ||||
| Centre of Breast Cancer of The Fourth Hospital of Hebei Medical University (Shijiazhuang Hebei) [42] | Asian | MAGE-A: 76.5% (n = 17) |
IHC | MAGE-A Antibody (6C1), Santa Cruz Biotechnology(USA) | ||||
| University Hospital Center Zagreb [39] | Caucasian | MAGE-A: 85.7% (n = 49) |
IHC | 3DA3 Monoclonal Antibody | ||||
| Split University Hospital Centre, Croatia [44] | Caucasian | MAGE-A1 Specific: 69.2% (n = 81) |
IHC | Monoclonal Antibody 77B | ||||
| Multi-MAGE: 58% (n = 81) |
IHC | Monoclonal Antibody 57B | ||||||
| MAGE-A10: 16% (n = 81) |
IHC | Monoclonal Antibody 3GA11 | ||||||
| European Institute of Oncology (Milan, Italy) [33] | Caucasian | MAGE-A: 32% (n = 50) |
IHC | Antibody cocktail of monoclonal antibodies 6C1, MA454, M3H67 and 57B | ||||
| Copenhagen University Hospital [45] | Caucasian | MAGE-A: 33% (n = 78) |
IHC | Rabbit polyclonal anti-peptide antibody EP101638 (rab Ab 1982) raised against Mage-4, Eurogentec (Belgium) | ||||
| National Cancer Institute (Milan, Italy) [43] | Caucasian | MAGE-A: 85.7–93% (n = 21) |
IHC | MAGE-A3 (Clone 60054-1-Ig) Monoclonal Antibody, Proteinthec (USA) | ||||
| Mesothelin (MSLN) | GPI-anchored membrane protein | Perelman School of Medicine, University of Pennsylvania [46] | Caucasian | 67% (n = 99) |
IHC | Mesothelin Monoclonal Antibody (clone 5B2), Thermo Scientific (USA) | MSLN is significantly expressed in TNBC compared to non-TNBC and is an independent prognostic marker associated with distant metastasis and worse survival. | [46,47,48] |
| University of Texas MD Anderson Cancer Center [48] | Caucasian | 34% (n = 109) |
IHC | Mesothelin Monoclonal Antibody (clone 5B2), Novocastra (USA) | ||||
| Prostate stem cell antigen (PSCA) | GPI-anchored membrane protein | University Hospital of Dresden, Germany [49] | Caucasian | 17% (n = 90) |
IHC | PSCA antibody MB1 | Distribution of PSCA expression among TNBC was comparable to the total population. Patients with PSCA-positive invasive micropapillary carcinoma (IMPC) of the breast had decreased disease-free survival. | [49,50] |
| Receptor tyrosine kinase-like orphan receptor 2 (ROR2) | Tyrosine kinase receptor family | University of New South Wales [51] | Caucasian | 87% (n = 295, breast cancer including triple- negative) |
IHC | Human ROR2 polyclonal antibody, Sigma-Aldrich (Australia) | Breast cancer patients including TNBC expressing ROR2 had significantly worse prognoses with shorter overall survival compared to those lacking ROR2. | [51] |
| Sperm protein associated with the nucleus X-linked (SPANX) | Sperm function | University of Texas Health Science Center [52] | Caucasian | 73% (n = 15) |
IHC | SPANXB1 (#H00728695), Abnova (Taiwan) | SPANXB1 was frequently overexpressed in human primary and metastatic TNBC. In ER-negative patients, elevated SPANX-A/C/D was correlated with shorter distant metastasis-free survival time. | [52,53] |
| CTAs associated with better prognosis in TNBC | ||||||||
| New York oesophageal squamous cell carcinoma-1 (NY-ESO-1) | Unknown; might be involved in cell cycle progression and growth | New York Presbyterian Hospital-Weill Cornell Medical Center and UCSF Medical Center [35] | Caucasian | 19.2% (n = 50) |
IHC | NY-ESO-1 Monoclonal Antibody(E978) produced in author’s laboratory | Higher expression of NY-ESO-1 was detected in TNBC. NY-ESO-1 expression was correlated with tumour-infiltrating lymphocytes and associated with good prognosis. | [33,35,39,40,43,54,55,56,57] |
| University Hospital Center Zagreb [39] | Caucasian | 10% (n = 50) |
IHC | NY-ESO-1 Monoclonal Antibody (B9.8.1.1) | ||||
| Roswell Park Cancer Institute [54] | Caucasian | 16% (n = 168) |
IHC | NY-ESO-1 Mouse Monoclonal, Zymed/Invitrogen (USA) | ||||
| Asan Medical Centre, Korea [56] | Asian | 9.3% (n = 172) |
IHC | NY-ESO-1 Monoclonal Antibody (E978), Invitrogen (USA) | ||||
| Royal Brisbane Women’s hospital [40] | Caucasian | ~20% (n = 65) |
IHC | NY-ESO-1 Antibody (E978), Santa Cruz Biotechnology(USA) | ||||
| National Cancer Institute (Milan, Italy) [43] | Caucasian | 28.6% (n = 21) |
IHC | NY-ESO-1 Monoclonal Antibody (E978), Invitrogen (USA) | ||||
| European Institute of Oncology (Milan, Italy) [57] | Caucasian | 16% (n = 50) |
IHC | NY-ESO-1 Monoclonal antibody (E978) provided by Ludwig Institute for Cancer Research | ||||
| CTAs with oncogenic potential | ||||||||
| Melanoma antigen gene (MAGE) | Not known. May promote tumourigenesis and metastasis. | See Above | Promote tumourigenesis and metastasis via various mechanisms such as acting as master regulator of E3 RING ubiquitin ligase, inhibiting p53 tumour suppressor or by enhancing cell motility. | [33,34,35,36,37,38,39] | ||||
| New York oesophageal squamous cell carcinoma-1 (NY-ESO-1) | Unknown; might be involved in cell cycle progression and growth | See Above | Might be involved in cellular proliferation and growth. | [21] | ||||
| Preferentially expressed antigen of melanoma (PRAME) | Membrane-bound protein | National Cancer Institute (Milan, Italy) [43] | Caucasian | 85.7–96.6% (n = 21) | IHC | PRAME Polyclonal Antibody (Clone NBP1-85418), Novus Boilogicals (USA) | Role in EMT reprogramming. Expression of PRAME was associated with negative ER status. |
[58,59,60] |
| Sperm-associated antigen 9 (SPAG9) | Sperm function | National Institute of Immunology, Aruna Asaf Ali Marg, (New Delhi, India) [61] | Asian | NA | IHC | Polyclonal antibody to SPAG9 was prepared in authors’ laboratory | Analysis of 100 breast cancer tissues (94 infiltrating ductal carcinomas [IDC], 2 ductal carcinomas in situ [DCIS] and 4 invasive lobular carcinomas [ILC]) revealed that 88% of samples stained positive for SPAG9. Role in invasiveness of breast cancer. Downregulation could reduce invasive potential of TNBC. | [61,62] |
| Sperm protein associated with the nucleus X-linked (SPANX) | Sperm function | See Above | Required for metastasis. Interacts with lamin A/C at the inner nuclear membrane and involved in the formation of actin-rich cellular protrusions that reorganise the extracellular matrix. | [52,53] | ||||
| Testes-specific protease 50 (TSP50) | Oncogene | Northeast Normal University (Changchun, China) | Caucasian | NA | IHC | TSP50 Monoclonal Antibody was prepared in authors’ laboratory | Analysis of 88 clinical breast cancer tissue microarrays (BR955 and BR 1101 from US Biomax, Rockville, MD, USA) revealed that 90.9% of specimens stained positive for TSP50 compared to 10% of adjacent normal tissues. Role in cell growth. Knockdown of TSP50 in breast cancer cells significantly inhibits cellular proliferation. TSP50-positive tumours were associated with negative ER expression and higher grade. | [63,64] |
| Zinc-finger protein 165 (ZNF165) | Gene regulation | Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas [27] | Caucasian | 90% (n = 10) |
IHC | ZNF165 (H00007718), Novus Biologicals (USA) | Enhances growth and survival of human TNBC cells both in vitro and in vivo by regulating TGF-β signalling. Frequently overexpressed in TNBC. | [27,65] |
| Tripartite motif containing 27 (TRIM27) | Gene regulation | Simmons Comprehensive Cancer Center, UT-Southwestern Medical Center, Dallas [27] | Caucasian | NA | TCGA | TRIM27 expression was significantly elevated in TNBC compared to normal breast tissue based on TCGA data. Displayed difference in cellular localisation, as it was mainly cytoplasmic in normal breast epithelia and more nuclear in TNBC tissues. Regulates TGFβ-dependent transcription in complex with ZNF165, ZNF446 and SMAD in TNBC. |
[27,65] | |
| Other CTAs with increased expression in TNBC | ||||||||
| Actin like 8 (ACTL8) | Cellular architecture | National Centre for Tumour Diseases (Heidelberg, Germany) [66] | Caucasian | 57% (n = 98, TCGA) |
TCGA | Frequently expressed in TNBC based on in silico analysis. | [66] | |
| Chromosome X open reading frame 6/ mastermind-like domain containing 1/Kita-Kyu-Shu lung cancer antigen-1 (CXorf6/MAMDL1/KK-LC-1/CT83) | Development of male genitalia Not known |
Johannes Gutenberg-University (Mainz, Germany) [67] | Caucasian | 64.7% (n = 17, from commercial vendor) |
IHC | Anti-CXorf61-A polyclonal antibody | Frequently expressed in TNBC. | [67] |
| Kitasato University Medical Center (Japan) [68] | Asian | 100% (n = 8) |
IHC | Mouse monoclonal antibody was prepared by CLEA Japan (Japan) | Frequently expressed in TNBC based on in silico analysis. Frequently overexpressed in TNBC and tumours without ER expression. | [66,68] | ||
| Sperm protein 17 (SP17) | Sperm function | University of Texas MD Anderson Cancer [69] | Caucasian | 47.2% (n = 36) |
IHC | Antibody against SP17 | SP17 is frequently expressed in primary breast tumours and in TNBC. | [69] |
| Wilms tumour-1 (WT-1) | Transcription factor | European Institute of Oncology (Milan, Italy) [57] | Caucasian | 54% (n = 27) |
IHC | WT1 Monoclonal Antibody (Clone WT49), Monosan (Netherlands) | Highest expression in TNBC compared to other breast cancer subtypes. | [57] |