Low Expression and Promoter Hypermethylation of the Tumour Suppressor SLIT2, are Associated with Adverse Patient Outcomes in Diffuse Large B Cell Lymphoma.

Mohamed, Ghada and Talima, Soha and Li, Lili and Wei, Wenbin and Rudzki, Zbigniew and Allam, Rasha Mahmoud and Simmons, William and Tao, Qian and Murray, Paul G (2019) Low Expression and Promoter Hypermethylation of the Tumour Suppressor SLIT2, are Associated with Adverse Patient Outcomes in Diffuse Large B Cell Lymphoma. Pathology oncology research : POR. ISSN 1532-2807. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Official URL: https://link.springer.com/article/10.1007%2Fs12253...

Abstract

SLIT2 has been classified as a major tumour suppressor gene due to its frequent inactivation in different cancer types. However, alterations of SLIT2 expression and relation to patient outcomes in diffuse large B cell lymphoma (DLBCL) remain undefined. The aim of this study was to investigate the expression and the methylation status of SLIT2 gene as well as its relation to patient outcomes in DLBCL. Immunohistochemical (IHC) staining was carried out to detect the expression of SLIT2 in a series of 108 DLBCL cases. Re-analysis of previously published dataset (GSE10846) that measured gene expression in DLBCL patients who had received CHOP or R-CHOP therapy was performed to identify associations between SLIT2 and patients survival. Laser capture microdissection was performed to isolate GC B cells and DLBCL primary tumor cells. Bisulfite treatment and methylation-specific PCR (MSP) analysis were done to assess SLIT2 promotor methylation status. We report that the expression of SLIT2 protein was reduced in a subset of DLBCL cases and this was significantly correlated with advanced clinical stage (p = 0.041) and was an independent predictor of worse overall survival (OS) (p = 0.012). Re-analysis of published gene expression data showed that reduced SLIT2 mRNA expression was significantly correlated with worse OS in R-CHOP-treated ABC DLBCL patients (p = <0.01). Hypermethylation of the SLIT2 promotor was significantly correlated with low SLIT2 expression (p = 0.009). Our results provide a novel evidence of reduced expression of SLIT2 that is associated with promoter hypermethylation and adverse outcomes in patients with DLBCL.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QZ Pathology. Oncology
Divisions: Clinical Support > Pathology
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Depositing User: Mr Philip O'Reilly
Date Deposited: 19 Mar 2019 11:48
Last Modified: 19 Mar 2019 11:48
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1936

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