The Novel Diagnostic Techniques and Biomarkers of Canine Mammary Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Diagnostic Techniques
2.1. Cytology and Histological Grade of Canine mammary Tumors
2.2. Evaluation of Selected Methods of Ultrasound Examination of Mammary Tumors in Bitches
3. Biomarkers of Canine Mammary Tumors
3.1. Various Cell Markers of the Cancer Process
3.1.1. Cell Cycle Markers
3.1.2. Proliferation Markers
3.1.3. Apoptosis Markers
3.2. Metastatic Potential and Prognosis of the Tumor
3.2.1. Cadherins
3.2.2. CEA
3.2.3. CA 15-3
3.3. Hormone Receptors
3.4. “Metabolomic” Markers
3.5. Gene Expression
3.6. miRNA
3.7. Transcriptome Sequencing
3.8. Inflammatory Markers
3.8.1. Inflammatory Cells Infiltration
3.8.2. Other Inflammatory Tissue and Blood CMTs Markers
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
APPs | acute phase proteins |
ARFI | Acoustic Radiation Force Impulse |
Ca15-3 | cancer antigen 15-3 |
CDK | cyclin -dependent kinases |
CEA | carcinoembryonic antigen |
CEUS | contrast-enhanced ultrasound |
CCL2 | CC chemokine ligand 2 |
CGS | cytological grading system |
CMT | canine mammary tumor |
CMTs | canine mammary tumors |
COX-2 | cyclo-oxygenase-2 |
CRP | C- reactive protein |
DEGs | differentially expressed genes |
E-cadherin | epithelial cadherin |
ER | estrogen receptor |
ER+ | estrogen receptor positive |
ER- | estrogen receptor negative |
FNAC | fine needle aspiration cytology |
HER-2 | human epidermal receptor 2 |
HSPs | heat shock proteins |
HBC | human breast cancer |
HBCs | human breast cancers |
iNOS | isoform of nitric oxide |
iTIM | intratumoral tumor-infiltrating macrophages |
Ki-67 | antigen Ki-67 |
miRNA | microRNAs |
MS | mass spectrometry |
NOS | invasive ductal carcinoma |
NMR | nuclear magnetic resonance |
OHE | ovariohysterectomy |
OTR | oxytocin receptor |
PD-1 | programmed cell death protein-1 |
PR | progesterone receptor |
PR+ | progesterone receptor positive |
PR- | progesterone receptor negative |
SR | strain ratio |
SSMC | staging system of mammary carcinomas |
sTIMs | stromal tumor-infiltrating macrophages |
VEGF | vascular endothelial growth factor |
VEGFR2 | vascular endothelial growth factor receptor 2 |
TIMs | tumor-infiltrating macrophages |
TGF-β1 | tumor growth factor-β1 |
TNBC | triple-negative breast cancer |
TNF-α | tumor necrosis factor-α |
TNM | tumor size (T), nodal stage (N), distant metastasis (M) |
tTIMs | total count tumor-infiltrating macrophages |
WES | whole-exome sequencing |
WTS | whole-transcriptome sequencing |
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Biomarker/Biomarkers | Function | Main Finding | References |
---|---|---|---|
cycylin D1, cyclin E1, | Cell cycle | cyclin D1 overexpression is commonly related with metastasis and shorter life expectancy | [43,44,45,46,47,48,49,50,51,52] |
Ki-67, PCNA | Proliferation | expression of Ki-67 and PCNA positively correlates with cancer progression | [53,54,55,56,57,58,59,60] |
HER-2 | Proliferation | there is a correlation between HER-2 expression and tumor mitotic index, high histological grade, and tumor size | [62,63,64,65,66,67] |
PD-1 | Apoptosis | most canine mammary tumor show expression of the PD-L1 | [68,69,70,71,72,73,74,75,76,77,78,79,80,81,82] |
p53 | Apoptosis | p53 expression was connected with high proliferative activity and high histological grade | [83,84,85,86,87,88,89,90] |
E-cadherin | Cell adhesion | downregulation of E-cadherin expression is connected with increased tumor growth and disease spreading, tumor malignancy, the aggressiveness of metastases, and short life expectancy | [91,92,93,94,95] |
CEA, CA 15-3 | Cell adhesion | both positively correlate with the presence of metastases, tumor dimension, and histological grade, it is recommended for them to be evaluated together | [96,97,98,99,100,101,102,103,104,105,106] |
ER, PR | Hormone receptors | the expression of ER or PR was more common in non-malignant tumors, and usually was connected with better clinical outcome | [107,108,109,110,111,112,113,114,115,116,117,118,119] |
5-hydroxyindolacetic acid, serotonin, indoxyl sulphate, and kynurenic acid, 3,4-dihydroxy-L-phenylalanine and epinephrine | Metabolites of tyrosine and tryptophan | detected in samples of the urine in CMTs patients | [125,126] |
HYAL-1 | Gene encoding lysosomal hyaluronidase | a possible biomarker linked with cell growth, migration, invasion, and angiogenesis | [132] |
BRCA1, BRCA2 | Genes involved in DNA repair | The 97.9% of dogs with CMT had one up to three genetic variations out of the seven | [134,135,136,137] |
miR-214 and miR-126 | miRNA | remarkably up-regulated in serum of bitches with mammary carcinoma | [143] |
miR-18a | miRNA | seemed to be a good prognostic factor | [139] |
miR-21 | miRNA | be more sensitive than other commonly used markers | [144] |
CD204+ macrophages | Inflammatory cell infiltration | In dogs with III grade CMTs, the number of CD204-positive macrophages was greater than in grades I and II | [151] |
LT CD3+, LTCD4+ | Inflammatory cell infiltration | high CD3+ and CD4+ cells in the tumor tissue correlate with shorter survival time | [152] |
LT FoxP3+ | Inflammatory cell infiltration | a big number of intratumoral FoxP3+ cells was related to defective differentiation of tumors, high histological grade of malignancy, and increased angiogenesis, thus guarded prognosis | [153] |
COX-2 | Inflammatory markers | increased expression is correlated with the histological grade of malignancy | [161] |
VEGF, TNF-α, TGF-β1 | pro-inflammatory and pro-tumoral cytokines and chemokines | CMT cytokines expression seems to be a marker of canine mammary tumors malignancy | [162] |
MCP-1, MCP-2, PDGF-BB, RANTES, SCF | pro-inflammatory cytokines | expressed in tumors with higher aggressiveness | [164] |
IL-35 | interleukin | connected with worse overall survival by increased histological grade of malignancy, mitotic index, neoplastic intravascular emboli, and lymph node metastasis | [165] |
CXCR3, CCR2, IL-4, IL-12p40 | pro-inflammatory cytokines and interleukines | cytokines connected with T lymphocyte activity are upregulated | [166] |
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Kaszak, I.; Witkowska-Piłaszewicz, O.; Domrazek, K.; Jurka, P. The Novel Diagnostic Techniques and Biomarkers of Canine Mammary Tumors. Vet. Sci. 2022, 9, 526. https://doi.org/10.3390/vetsci9100526
Kaszak I, Witkowska-Piłaszewicz O, Domrazek K, Jurka P. The Novel Diagnostic Techniques and Biomarkers of Canine Mammary Tumors. Veterinary Sciences. 2022; 9(10):526. https://doi.org/10.3390/vetsci9100526
Chicago/Turabian StyleKaszak, Ilona, Olga Witkowska-Piłaszewicz, Kinga Domrazek, and Piotr Jurka. 2022. "The Novel Diagnostic Techniques and Biomarkers of Canine Mammary Tumors" Veterinary Sciences 9, no. 10: 526. https://doi.org/10.3390/vetsci9100526