Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival.

Association of Glioblastoma Multiforme Stem Cell Characteristics, Differentiation, and Microglia Marker Genes with Patient Survival.
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DOI:
10.1155/2018/9628289
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发表时间:
2018
影响因子:
4.3
通讯作者:
Schroeder HWS
Schroeder HWS
中科院分区:
医学3区
文献类型:
--
作者:
Bien-Möller S;Balz E;Herzog S;Plantera L;Vogelgesang S;Weitmann K;Seifert C;Fink MA;Marx S;Bialke A;Venugopal C;Singh SK;Hoffmann W;Rauch BH;Schroeder HWS

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多形性胶质母细胞瘤(GBM)患者尽管接受了多模式治疗,但仍有较高的复发风险。据推测,胶质瘤干细胞(GSC)负责GBM的治疗抗性。特异性GSC标志物的鉴定可能有助于开发靶向治疗。在这里,我们进行了干细胞(ABCG 2,CD 44,CD 95,CD 133,ELF 4,Nanog和Nestin)以及分化和小胶质细胞标记物(GFAP,Iba 1和Sparc)在GBM中的表达分析,并与非恶性脑进行比较。此外,分析了这些蛋白质对患者存活的作用及其在LN 18干细胞样神经球中的表达。在mRNA水平,ABCG 2和CD 95减少,GFAP不变;所有其他研究的标志物在GBM中增加。在蛋白水平,CD 44,ELF 4,Nanog,Nestin和Sparc在GBM中升高,但只有CD 133和Nestin与生存时间密切相关。此外,在LN 18神经球中ABCG 2和GFAP表达降低,而CD 44、CD 95、CD 133、ELF 4、Nanog、Nestin和Sparc上调。总的来说,只有CD 133和巢蛋白与生存率相关。这引起了关于其他靶结构作为预后标志物的适用性的担忧,但使得CD 133和巢蛋白都成为GBM治疗的候选者。然而,寻找更特异的标记蛋白是迫切需要的。
Patients with glioblastoma multiforme (GBM) are at high risk to develop a relapse despite multimodal therapy. Assumedly, glioma stem cells (GSCs) are responsible for treatment resistance of GBM. Identification of specific GSC markers may help to develop targeted therapies. Here, we performed expression analyses of stem cell (ABCG2, CD44, CD95, CD133, ELF4, Nanog, and Nestin) as well as differentiation and microglia markers (GFAP, Iba1, and Sparc) in GBM compared to nonmalignant brain. Furthermore, the role of these proteins for patient survival and their expression in LN18 stem-like neurospheres was analyzed. At mRNA level, ABCG2 and CD95 were reduced, GFAP was unchanged; all other investigated markers were increased in GBM. At protein level, CD44, ELF4, Nanog, Nestin, and Sparc were elevated in GBM, but only CD133 and Nestin were strongly associated with survival time. In addition, ABCG2 and GFAP expression was decreased in LN18 neurospheres whereas CD44, CD95, CD133, ELF4, Nanog, Nestin, and Sparc were upregulated. Altogether only CD133 and Nestin were associated with survival rates. This raises concerns regarding the suitability of the other target structures as prognostic markers, but makes both CD133 and Nestin candidates for GBM therapy. Nevertheless, a search for more specific marker proteins is urgently needed.
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