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MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours.

ABSTRACT: MicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans.Expression profiles of 317 microRNAs in 146 canine mammary tumours of different histological type, malignancy grade and clinical history (presence/absence of metastases) and in 25 control samples were evaluated. The profiling was performed using microarrays. Significance Analysis of Microarrays test was applied in the analysis of microarray data (both unsupervised and supervised data analyses were performed). Validation of the obtained results was performed using real-time qPCR. Subsequently, predicted targets for the microRNAs were searched for in miRBase.Results of the unsupervised analysis indicate that the primary factor separating the samples is the metastasis status. Predicted targets for microRNAs differentially expressed in the metastatic vs. non-metastatic group are mostly engaged in cell cycle regulation, cell differentiation and DNA-damage repair. On the other hand, the supervised analysis reveals clusters of differentially expressed microRNAs unique for the tumour type, malignancy grade and metastasis factor.The most significant difference in microRNA expression was observed between the metastatic and non-metastatic group, which suggests a more important role of microRNAs in the metastasis process than in the malignant transformation. Moreover, the differentially expressed microRNAs constitute potential metastasis markers. However, validation of cfa-miR-144, cfa-miR-32 and cfa-miR-374a levels in blood samples did not follow changes observed in the non-metastatic and metastatic tumours.

SUBMITTER: Bulkowska M

PROVIDER: S-EPMC5678797 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours.

Bulkowska Malgorzata M Rybicka Agata A Senses Kerem Mert KM Senses Kerem Mert KM Ulewicz Katarzyna K Witt Katarzyna K Szymanska Joanna J Taciak Bartlomiej B Klopfleisch Robert R Hellmén Eva E Dolka Izabella I Gure Ali O AO Mucha Joanna J Mikow Mariusz M Gizinski Slawomir S Krol Magdalena M

BMC cancer 20171107 1

<h4>Background</h4>MicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans.<h4>Methods</h4>Expression profiles of 317 microRNAs in 146 canine mamma ...[more]

PMID: 29115935

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Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. Thirteen simple mammary carcinomas with invasive growth and lymph node metastases at the time of tumor resection and 14 simple carcinomas without lymph node metastases were included in the study. None of the patients had radiographically detectable pulmonary metastases at the time of tumor resection. Distant metastases as the cause of death were determined postoperatively by radiographic detection of metastases or necropsy. Selection criteria for carcinomas without lymph node metastases included an invasive growth, a negative lymph node status, a histological grade III and a minimal tumor diameter above the average of the lymph node positive tumors (> 2.42 cm). All animals with non-metastatic carcinomas had a survival rate of over 24 months except animal no. 22 (2627) which developed radiographic detectable lung metastases 8 months after surgery. Tumor and lymph node histologies were evaluated independently by two board-certified pathologists, following the criteria of the WHO classification of canine mammary tumors and the Nottingham grading system. All 27 tumors were simple carcinomas and characterized by an invasive, mostly solid growth pattern, marked cellular pleomorphism, anisokaryosis and 3 or more mitotic figures per high power field.

Project description:BackgroundMammary gland tumours are the most frequently diagnosed tumours in the female dogs but just a few studies have analysed their epidemiology. Therefore, we set out to describe the epidemiology of canine mammary cancer in the Canary Archipelago, Spain. We analysed a pathology tumour registry (PTR) and identified 7362 samples obtained from 5240 female dogs resident on the Canary Archipelago during an 18-year period (2003-2020). Using a case-control study design, we compared mammary tumour affected dogs with the Canarian canine population registry in order to elucidate the breed associations for these tumours.ResultsThe frequency of a diagnosis of mammary tumours relative to all tumour diagnoses in female dogs decreased during the study period from 62.7% to 48.9%. Contemporaneously, the proportion of dogs diagnosed with mammary tumours who were also neutered increased from 13.6% to 26.9%. There was a negative correlation (R = -0.84) between these changes. Additional findings were that: the proportion of female dogs diagnosed with multiple tumours increased by 23.5% and that the proportion of malignant tumours 89.2% diagnosed has remained stable through the period. Benign mammary tumours were diagnosed at younger ages (9.2 years old) than carcinomas (9.7 years old) and sarcomas (10.4 years old). Epithelial mammary tumours were diagnosed at younger ages in entire female dogs. Samoyed, Schnauzer, Poodle, German Pinscher and Cocker Spaniel were the breeds with the highest odds-ratios (OR) in comparison with the reference (crossbreeds) while Miniature Pinscher, American Staffordshire Terrier, English Pointer as well as some local breeds such as the Canary Warren Hound and the Majorero had the lowest ORs.ConclusionsThis study provides a description of the changing epidemiology of canine mammary cancer in the Canary Archipelago over the last two decades. We found high rates of CMT with a significant predominance of malignant tumours. Exact risk factors are uncertain, but a combination of environmental, regional socioeconomic affecting human and their pets, and animal management factors are likely to play a part. Specifically, neutering was negatively associated with the proportion of epithelial mammary gland tumours and breeds native to the region were at lower risk of mammary tumours. A deeper analysis of all these factors will facilitate a deeper understanding of the epidemiology of mammary gland tumours in both the canine and the human population.

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MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours.

Publications

MicroRNA expression patterns in canine mammary cancer show significant differences between metastatic and non-metastatic tumours.

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