Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties
The impact of tumour associated stroma on cancer metastasis is an emerging field. However, cancer associated genes in peritumoral adipose tissue (pAT) in human colon cancer have not been explored. The aim of this study was to identify differentially expressed genes (DEGs) associated with cancer path...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2430 |
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| author | Maria Tabuso Raghu Adya Richard Stark Kishore Gopalakrishnan Yee Wah Tsang Sean James Andrew White Adrian Fisk Federica Dimitri Mark Christian Ramesh Pulendran Arasaradnam |
| author_facet | Maria Tabuso Raghu Adya Richard Stark Kishore Gopalakrishnan Yee Wah Tsang Sean James Andrew White Adrian Fisk Federica Dimitri Mark Christian Ramesh Pulendran Arasaradnam |
| author_sort | Maria Tabuso |
| collection | DOAJ |
| description | The impact of tumour associated stroma on cancer metastasis is an emerging field. However, cancer associated genes in peritumoral adipose tissue (pAT) in human colon cancer have not been explored. The aim of this study was to identify differentially expressed genes (DEGs) associated with cancer pathways in mesenteric pAT compared with adjacent adipose tissue. In total, nine patients with colon cancer pathological stage T2/T4 were employed in this study. DEGs were identified in 6 patients employing Nanostring PanCancer Pathway Panel and pathway enrichment analyses were performed. Differential expression of the 5 most up-regulated and 2 down regulated genes was validated with qRT-PCR. Results showed collagen type I alpha 1 chain (<i>COL1A1</i>) <i>p</i> = 0.007; secreted frizzled related protein (<i>SFRP2</i>) <i>p</i> = 0.057; fibroblast growth factor 7 (<i>FGF7</i>) not significant (ns); phospholipase A2, group IIA (<i>PLA2G2A</i>) ns; nerve growth factor receptor (<i>NGFR</i>) ns; lymphoid enhancer binding factor 1 (<i>LEF1</i>) <i>p</i> = 0.03; cadherin 1, Type 1, E-cadherin (epithelial) (<i>CDH1</i>) 0.09. Results have highlighted down-regulation of the Wingless/Integrated (Wnt) pathway in mesenteric pAT compared to distal adipose tissue. Highly upregulated genes in mesenteric pAT were involved in extracellular matrix (ECM)-receptor interactions and focal adhesion. Highly down regulated genes were involved in the cell cycle. Immunohistochemistry revealed differential distribution of COL1A1 showing maximum levels in tumour tissue and gradually decreasing in distant adipose tissue. <i>COL1A1</i> and down regulation of Wnt pathway may have a role in local invasion and distant metastasis. <i>COL1A1</i> may represent a stromal prognostic biomarker and therapeutic target in colon cancer. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T06:12:51Z |
| publishDate | 2021-02-01 |
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| spelling | doaj.art-9daad9176d244e35b6fff29b248a19a52023-12-03T11:56:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225243010.3390/ijms22052430Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic PropertiesMaria Tabuso0Raghu Adya1Richard Stark2Kishore Gopalakrishnan3Yee Wah Tsang4Sean James5Andrew White6Adrian Fisk7Federica Dimitri8Mark Christian9Ramesh Pulendran Arasaradnam10Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UKWarwick Medical School, University of Warwick, Coventry CV4 7AL, UKSchool of Life Sciences, University of Warwick, Coventry CV4 7AL, UKDepartment of Pathology, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UKDepartment of Pathology, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UKDepartment of Biomedical Sciences, University Hospital Coventry & Warwickshire, Coventry CV2 2DX, UKDepartment of Biomedical Sciences, University Hospital Coventry & Warwickshire, Coventry CV2 2DX, UKDepartment of Biomedical Sciences, University Hospital Coventry & Warwickshire, Coventry CV2 2DX, UKDepartment of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UKDepartment of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UKDepartment of Gastroenterology, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UKThe impact of tumour associated stroma on cancer metastasis is an emerging field. However, cancer associated genes in peritumoral adipose tissue (pAT) in human colon cancer have not been explored. The aim of this study was to identify differentially expressed genes (DEGs) associated with cancer pathways in mesenteric pAT compared with adjacent adipose tissue. In total, nine patients with colon cancer pathological stage T2/T4 were employed in this study. DEGs were identified in 6 patients employing Nanostring PanCancer Pathway Panel and pathway enrichment analyses were performed. Differential expression of the 5 most up-regulated and 2 down regulated genes was validated with qRT-PCR. Results showed collagen type I alpha 1 chain (<i>COL1A1</i>) <i>p</i> = 0.007; secreted frizzled related protein (<i>SFRP2</i>) <i>p</i> = 0.057; fibroblast growth factor 7 (<i>FGF7</i>) not significant (ns); phospholipase A2, group IIA (<i>PLA2G2A</i>) ns; nerve growth factor receptor (<i>NGFR</i>) ns; lymphoid enhancer binding factor 1 (<i>LEF1</i>) <i>p</i> = 0.03; cadherin 1, Type 1, E-cadherin (epithelial) (<i>CDH1</i>) 0.09. Results have highlighted down-regulation of the Wingless/Integrated (Wnt) pathway in mesenteric pAT compared to distal adipose tissue. Highly upregulated genes in mesenteric pAT were involved in extracellular matrix (ECM)-receptor interactions and focal adhesion. Highly down regulated genes were involved in the cell cycle. Immunohistochemistry revealed differential distribution of COL1A1 showing maximum levels in tumour tissue and gradually decreasing in distant adipose tissue. <i>COL1A1</i> and down regulation of Wnt pathway may have a role in local invasion and distant metastasis. <i>COL1A1</i> may represent a stromal prognostic biomarker and therapeutic target in colon cancer.https://www.mdpi.com/1422-0067/22/5/2430colon canceradipose tissueextracellular matrixtumour microenvironment |
| spellingShingle | Maria Tabuso Raghu Adya Richard Stark Kishore Gopalakrishnan Yee Wah Tsang Sean James Andrew White Adrian Fisk Federica Dimitri Mark Christian Ramesh Pulendran Arasaradnam Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties International Journal of Molecular Sciences colon cancer adipose tissue extracellular matrix tumour microenvironment |
| title | Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties |
| title_full | Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties |
| title_fullStr | Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties |
| title_full_unstemmed | Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties |
| title_short | Fibrotic Phenotype of Peritumour Mesenteric Adipose Tissue in Human Colon Cancer: A Potential Hallmark of Metastatic Properties |
| title_sort | fibrotic phenotype of peritumour mesenteric adipose tissue in human colon cancer a potential hallmark of metastatic properties |
| topic | colon cancer adipose tissue extracellular matrix tumour microenvironment |
| url | https://www.mdpi.com/1422-0067/22/5/2430 |
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