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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0208656 |
| _version_ | 1818925350721159168 |
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| author | Shahid Hussain Sonal Saxena Sameer Shrivastava Ashok Kumar Mohanty Sudarshan Kumar Rajkumar James Singh Abhinav Kumar Sajad Ahmad Wani Ravi Kumar Gandham Naveen Kumar Anil Kumar Sharma Ashok Kumar Tiwari Raj Kumar Singh |
| author_facet | Shahid Hussain Sonal Saxena Sameer Shrivastava Ashok Kumar Mohanty Sudarshan Kumar Rajkumar James Singh Abhinav Kumar Sajad Ahmad Wani Ravi Kumar Gandham Naveen Kumar Anil Kumar Sharma Ashok Kumar Tiwari Raj Kumar Singh |
| author_sort | Shahid Hussain |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T02:39:50Z |
| format | Article |
| id | doaj.art-d7ca5b30a8184a2e8cf51c44a9d61485 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:39:50Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-d7ca5b30a8184a2e8cf51c44a9d614852022-12-21T19:56:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-011312e020865610.1371/journal.pone.0208656Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis.Shahid HussainSonal SaxenaSameer ShrivastavaAshok Kumar MohantySudarshan KumarRajkumar James SinghAbhinav KumarSajad Ahmad WaniRavi Kumar GandhamNaveen KumarAnil Kumar SharmaAshok Kumar TiwariRaj Kumar SinghSpontaneously 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.https://doi.org/10.1371/journal.pone.0208656 |
| spellingShingle | Shahid Hussain Sonal Saxena Sameer Shrivastava Ashok Kumar Mohanty Sudarshan Kumar Rajkumar James Singh Abhinav Kumar Sajad Ahmad Wani Ravi Kumar Gandham Naveen Kumar Anil Kumar Sharma Ashok Kumar Tiwari Raj Kumar Singh Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis. PLoS ONE |
| title | Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis. |
| title_full | Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis. |
| title_fullStr | Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis. |
| title_full_unstemmed | Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis. |
| title_short | Gene expression profiling of spontaneously occurring canine mammary tumours: Insight into gene networks and pathways linked to cancer pathogenesis. |
| title_sort | gene expression profiling of spontaneously occurring canine mammary tumours insight into gene networks and pathways linked to cancer pathogenesis |
| url | https://doi.org/10.1371/journal.pone.0208656 |
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