Related Experiment Video
Updated: Feb 15, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma
Yuen Yee Cheng1, Ellie Mok1, Sarah Tan2
1Asbestos Diseases Research Institute (ADRI), University of Sydney, Sydney, NSW, Australia.
Abstract:
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.
Insights
Secreted frizzled-related sequence (SFRP) genes act as tumor suppressors in malignant pleural mesothelioma (MPM). Methylation of SFRP2 and SFRP5 is common in MPM and detectable in patient plasma, suggesting biomarker potential.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Malignant pleural mesothelioma (MPM) is linked to asbestos exposure, causing chronic inflammation and potential tumor suppressor gene silencing.
- The Wnt signaling pathway is implicated in various cancers, including MPM, and its dysregulation can be influenced by inflammation.
- Secreted frizzled-related sequence (SFRP) genes function as Wnt pathway antagonists and are recognized as potential tumor suppressors in multiple cancer types.
Purpose of the Study:
- To investigate the expression and DNA methylation status of SFRP genes in MPM.
- To confirm the tumor-suppressive role of SFRP2 and SFRP5 in MPM.
- To assess the potential of methylated SFRP DNA as a biomarker in MPM patient plasma.
Main Methods:
- Analysis of SFRP gene expression and DNA methylation in MPM cell lines and 66 patient FFPE samples.
- Demethylation treatment of MPM cell lines to observe effects on gene expression.
- Detection of methylated SFRP DNA in MPM patient plasma samples.
Main Results:
- High methylation rates observed for SFRP2 (56%) and SFRP5 (70%) in MPM patient samples.
- SFRP2 and SFRP5 demonstrated confirmed tumor-suppressive activity in MPM cell lines.
- Long-term asbestos exposure reduced SFRP1 and SFRP2 expression in mesothelial cells via epigenetic changes.
- Methylated SFRP DNA, particularly SFRP2 and SFRP5, was detectable in MPM patient plasma.
Conclusions:
- SFRP genes exhibit tumor-suppressive activity in malignant pleural mesothelioma.
- Epigenetic alterations, specifically DNA methylation, play a role in SFRP gene regulation in MPM, potentially influenced by asbestos exposure.
- Methylated DNA from SFRP gene promoters in plasma shows promise as a non-invasive biomarker for MPM detection and monitoring.
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