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溴结构域和 PHD 手指转录因子促进神经胶质瘤的进展并预示不良预后。

Bromodomain PHD‑finger transcription factor promotes glioma progression and indicates poor prognosis.

机构信息

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Department of Radiation Oncology, Haikou People's Hospital, Haikou, Hainan 570208, P.R. China.

出版信息

Oncol Rep. 2019 Jan;41(1):246-256. doi: 10.3892/or.2018.6832. Epub 2018 Oct 30.

Abstract

Glioma is one of the most deadly central nervous system tumors around the world. Uncontrollable cell proliferation and invasion are key factors of cancer progression as well as glioma. Available evidence suggests that bromodomain PHD‑finger transcription factor (BPTF) plays an important role in stem cell proliferation and differentiation, as well as in progression of some tumors, but there is little data on glioma. Therefore, the present study aimed to explore the functional role and potential clinical value of BPTF in glioma. Public database, real‑time PCR and western blotting were used to detect the expression of BPTF in glioma tissue and cells. The relationship between BPTF with clinicopathological features and the prognosis of glioma patients was analyzed by immunohistochemical staining in 113 cases of paraffin‑embedded primary glioma specimens. Furthermore, cytological experiments were conducted to elucidate the functional role of BPTF in glioma U251 cells, as well as the potential molecular mechanism. The expression of BPTF in glioma tissues was significantly higher than that in normal brain tissues. The association analysis results revealed that high BPTF expression was significantly associated with WHO grade and tumor size. Survival analysis revealed that the BPTF high‑expression group had poorer overall survival (OS) and progression‑free survival (PFS) compared with the low‑expression group. Univariate and multivariate Cox regression analyses revealed that BPTF expression was an independent prognostic factor for the OS and PFS of glioma patients. Cytological experiments revealed that BPTF overexpression could significantly promote the proliferation, migration and invasion of human glioma U251 cells. A study of the underlying mechanism indicated that BPTF promoted glioma progression via MYC signaling. Our results preliminarily indicated that BPTF promoted glioma progression via MYC signaling and may be a potential prognostic biomarker and therapeutic target for glioma patients.

摘要

神经胶质瘤是全世界最致命的中枢神经系统肿瘤之一。不受控制的细胞增殖和侵袭是癌症进展以及神经胶质瘤的关键因素。现有证据表明,溴结构域和 PHD 手指转录因子(BPTF)在干细胞增殖和分化以及某些肿瘤的进展中发挥着重要作用,但关于神经胶质瘤的研究数据较少。因此,本研究旨在探讨 BPTF 在神经胶质瘤中的功能作用及潜在的临床价值。通过公共数据库、实时 PCR 和 Western blot 检测神经胶质瘤组织和细胞中 BPTF 的表达。通过对 113 例石蜡包埋原发性神经胶质瘤标本进行免疫组织化学染色,分析 BPTF 与神经胶质瘤患者临床病理特征和预后的关系。此外,通过细胞学实验阐明 BPTF 在神经胶质瘤 U251 细胞中的功能作用及其潜在的分子机制。神经胶质瘤组织中 BPTF 的表达明显高于正常脑组织。关联分析结果表明,BPTF 高表达与 WHO 分级和肿瘤大小显著相关。生存分析显示,BPTF 高表达组的总生存期(OS)和无进展生存期(PFS)均较低表达组差。单因素和多因素 Cox 回归分析表明,BPTF 表达是神经胶质瘤患者 OS 和 PFS 的独立预后因素。细胞学实验表明,BPTF 过表达可显著促进人神经胶质瘤 U251 细胞的增殖、迁移和侵袭。对潜在机制的研究表明,BPTF 通过 MYC 信号促进神经胶质瘤的进展。我们的研究结果初步表明,BPTF 通过 MYC 信号促进神经胶质瘤的进展,可能是神经胶质瘤患者潜在的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b7d/6278589/d18031b66625/OR-41-01-0246-g00.jpg

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