Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis

Spontaneously occurring canine mammary tumours (CMTs) are the most common neoplasms of unspayed female dogs leading to thrice higher mortality rates than human breast cancer. These are also attractive models for human breast cancer studies owing to clinical and molecular similarities. Thus, they are...

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Bibliographic Details
Published in:PloS one 2018-12, Vol.13 (12), p.e0208656-e0208656
Main Authors: Hussain, Shahid, Saxena, Sonal, Shrivastava, Sameer, Mohanty, Ashok Kumar, Kumar, Sudarshan, Singh, Rajkumar James, Kumar, Abhinav, Wani, Sajad Ahmad, Gandham, Ravi Kumar, Kumar, Naveen, Sharma, Anil Kumar, Tiwari, Ashok Kumar, Singh, Raj Kumar
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Apoptosis
Benign
Bioindicators
Biological markers
Biology
Biology and Life Sciences
Biomarkers
Biotechnology
Bladder cancer
Breast cancer
Cancer
Cancer genetics
Cancer research
Cell cycle
Criminal investigation
Cyclin-dependent kinases
Cyclins
Dendritic cells
Deoxyribonucleic acid
Deregulation
DNA
DNA microarrays
DNA repair
Dog Diseases - genetics
Dog Diseases - metabolism
Dogs
Electrophoresis
Endothelial growth factors
Female
Gel electrophoresis
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genes
Genetic aspects
Health aspects
Health maintenance organizations
Histopathology
Identification
Kinases
Mammary gland
Mammary glands
Mammary Glands, Animal - metabolism
Mammary Neoplasms, Animal - genetics
Mammary Neoplasms, Animal - metabolism
Medical prognosis
Medical research
Medicine and Health Sciences
Microarray Analysis
Neoplasia
Neoplasms
Networks
Pancreatic cancer
Pathogenesis
Pathology
Patient outcomes
Polymerase Chain Reaction
Proteins
Proteomics
Recombination
Regulators
Research and Analysis Methods
Signal transduction
Signaling
Therapeutic applications
Tissue analysis
Tissues
Tumors
Vascular endothelial growth factor
Virology
Wnt protein
β-Catenin
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Summary:Spontaneously occurring canine mammary tumours (CMTs) are the most common neoplasms of unspayed female dogs leading to thrice higher mortality rates than human breast cancer. These are also attractive models for human breast cancer studies owing to clinical and molecular similarities. Thus, they are important candidates for biomarker studies and understanding cancer pathobiology. The study was designed to explore underlying molecular networks and pathways in CMTs for deciphering new prognostic factors and therapeutic targets. To gain an insight into various pathways and networks associated with the development and pathogenesis of CMTs, comparative cDNA microarray expression profiling was performed using CMT tissues and healthy mammary gland tissues. Upon analysis, 1700 and 1287 differentially expressed genes (DEGs, P ≤ 0.05) were identified in malignant and benign tissues, respectively. DEGs identified from microarray analysis were further annotated using the Ingenuity Systems Pathway Analysis (IPA) tool for detection of deregulated canonical pathways, upstream regulators, and networks associated with malignant, as well as, benign disease. Top scoring key networks in benign and malignant mammary tumours were having central nodes of VEGF and BUB1B, respectively. Cyclins & cell cycle regulation and TREM1 signalling were amongst the top activated canonical pathways in CMTs. Other cancer related significant pathways like apoptosis signalling, dendritic cell maturation, DNA recombination and repair, Wnt/β-catenin signalling, etc. were also found to be altered. Furthermore, seven proteins (ANXA2, APOCII, CDK6, GATC, GDI2, GNAQ and MYH9) highly up-regulated in malignant tissues were identified by two-dimensional gel electrophoresis (2DE) and MALDI-TOF PMF studies which were in concordance with microarray data. Thus, the study has uncovered ample number of candidate genes associated with CMTs which need to be further validated as therapeutic targets and prognostic markers.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0208656