Low Expression and Promoter Hypermethylation of the Tumour Suppressor SLIT2, are Associated with Adverse Patient Outcomes in Diffuse Large B Cell Lymphoma
Low Expression and Promoter Hypermethylation of the Tumour Suppressor SLIT2, are Associated with Adverse Patient Outcomes in Diffuse Large B Cell Lymphoma
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DOI：
10.1007/s12253-019-00600-9
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发表时间：
2019-07-01
影响因子：
2.8
通讯作者：
Murray, Paul G.
中科院分区：
文献类型：
--
作者：
Mohamed, Ghada;Talima, Soha;Murray, Paul G.
SLIT 2由于其在不同癌症类型中频繁失活而被分类为主要肿瘤抑制基因。然而，SLIT 2表达的改变及其与弥漫性大B细胞淋巴瘤（DLBCL）患者预后的关系仍不明确。本研究旨在探讨SLIT 2基因在DLBCL中的表达、甲基化状态及其与患者预后的关系。采用免疫组化（IHC）法检测SLIT 2在108例DLBCL中的表达。对先前发表的测量接受CHOP或R-CHOP治疗的DLBCL患者的基因表达的数据集（GSE 10846）进行再分析，以确定SLIT 2与患者生存之间的关联。进行激光捕获显微切割以分离GC B细胞和DLBCL原代肿瘤细胞。进行亚硫酸氢盐处理和甲基化特异性PCR（MSP）分析以评估SLIT 2启动子甲基化状态。我们报告SLIT 2蛋白表达在DLBCL病例的一个子集中降低，这与晚期临床分期显著相关（p=0.041），并且是总生存期（OS）较差的独立预测因子（p=0.012）。对已发表的基因表达数据的再分析显示，SLIT 2 mRNA表达降低与R-CHOP治疗的ABC DLBCL患者的OS恶化显著相关（p= 0.001）。
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=