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血浆GBP2启动子甲基化与乳腺癌的晚期阶段相关。

Plasma GBP2 promoter methylation is associated with advanced stages in breast cancer.

作者信息

Rahvar Farzaneh, Salimi Mahdieh, Mozdarani Hossein

机构信息

National Institute of Genetic Engineering and Biotechnology (NIGEB), Institute of Medical Biotechnology, Department of Medical Genetics, Tehran, Iran.

Tarbiat Modares University, Faculty of Medical Sciences, Department of Medical Genetics, Tehran, Iran.

出版信息

Genet Mol Biol. 2020 Nov 17;43(4):e20190230. doi: 10.1590/1678-4685-GMB-2019-0230. eCollection 2020.

Abstract

Blood methylated cell-free DNA (cfDNA) as a minimally invasive cancer biomarker has great importance in cancer management. Guanylate binding protein 2 (GBP2) has been considered as a possible controlling factor in tumor development. GBP2 gene expression and its promoter methylation status in both plasma cfDNA and tumor tissues of ductal carcinoma breast cancer patients were analyzed using SYBR green comparative Real-Time RT-PCR and, Methyl-specific PCR techniques, respectively in order to find a possible cancer-related marker. The results revealed that GBP2 gene expression and promoter methylation were inversely associated. GBP2 was down-regulated in tumors with emphasis on triple negative status, nodal involvement and higher cancer stages (p<0.0001). GBP2 promoter methylation on both cfDNA and tumor tissues were positively correlated and was detected in about 88% of breast cancer patients mostly in (Lymph node positive) LN+ and higher stages. Data provided shreds of evidence that GBP2 promoter methylation in circulating DNA may be considered as a possible effective non-invasive molecular marker in poor prognostic breast cancer patients with the evidence of its relation to disease stage and lymph node metastasis. However further studies need to evaluate the involvement of GBP2 promoter methylation in progression-free survival or overall survival of the patients.

摘要

血液甲基化游离DNA(cfDNA)作为一种微创癌症生物标志物在癌症管理中具有重要意义。鸟苷酸结合蛋白2(GBP2)被认为是肿瘤发展的一个可能控制因素。分别使用SYBR Green比较实时RT-PCR和甲基化特异性PCR技术分析导管癌乳腺癌患者血浆cfDNA和肿瘤组织中GBP2基因表达及其启动子甲基化状态,以寻找可能的癌症相关标志物。结果显示,GBP2基因表达与启动子甲基化呈负相关。GBP2在肿瘤中表达下调,尤其在三阴性状态、淋巴结受累和癌症分期较高的肿瘤中(p<0.0001)。cfDNA和肿瘤组织中GBP2启动子甲基化呈正相关,约88%的乳腺癌患者检测到GBP2启动子甲基化,主要见于淋巴结阳性(LN+)和较高分期患者。数据提供证据表明,循环DNA中GBP2启动子甲基化可能被视为预后不良乳腺癌患者一种可能有效的非侵入性分子标志物,因为其与疾病分期和淋巴结转移有关。然而,需要进一步研究评估GBP2启动子甲基化在患者无进展生存期或总生存期的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49c3/7783727/0db67fed5159/1415-4757-GMB-43-4-e20190230-gf01.jpg

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