SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma

Cheng, YY; Mok, E; Tan, S; Leygo, C; McLaughlin, C; George, AM; Reid, G

SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma

Cheng, YY Mok, E Tan, S Leygo, C McLaughlin, C George, AM

Reid, G

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Publication Type:: Journal Article
Citation:: Disease Markers, 2017, 2017
Issue Date:: 2017-01-01

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Field	Value	Language
dc.contributor.author	Cheng, YY	en_US
dc.contributor.author	Mok, E	en_US
dc.contributor.author	Tan, S	en_US
dc.contributor.author	Leygo, C	en_US
dc.contributor.author	McLaughlin, C	en_US
dc.contributor.author	George, AM https://orcid.org/0000-0003-4691-8960	en_US
dc.contributor.author	Reid, G https://orcid.org/0000-0001-6465-5223	en_US
dc.date.available	2017-10-16	en_US
dc.date.issued	2017-01-01	en_US
dc.identifier.citation	Disease Markers, 2017, 2017	en_US
dc.identifier.issn	0278-0240	en_US
dc.identifier.uri	http://hdl.handle.net/10453/125255
dc.description.abstract	© 2017 Yuen Yee Cheng et al. Malignant pleural mesothelioma (MPM) is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56%) and SFRP5 (70%) in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A) via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.	en_US
dc.relation.ispartof	Disease Markers	en_US
dc.relation.isbasedon	10.1155/2017/2536187	en_US
dc.subject.classification	Oncology & Carcinogenesis	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mesothelioma	en_US
dc.subject.mesh	Lung Neoplasms	en_US
dc.subject.mesh	Asbestos	en_US
dc.subject.mesh	Eye Proteins	en_US
dc.subject.mesh	Membrane Proteins	en_US
dc.subject.mesh	Carcinogens	en_US
dc.subject.mesh	DNA Methylation	en_US
dc.subject.mesh	Epigenesis, Genetic	en_US
dc.subject.mesh	Biomarkers, Tumor	en_US
dc.title	SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma	en_US
dc.type	Journal Article
utslib.citation.volume	2017	en_US
utslib.for	1116 Medical Physiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	2017	en_US

Abstract:

© 2017 Yuen Yee Cheng et al. Malignant pleural mesothelioma (MPM) is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56%) and SFRP5 (70%) in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A) via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.

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http://hdl.handle.net/10453/125255