Polat Bülent, Wohlleben Gisela, Kosmala Rebekka, Lisowski Dominik, Mantel Frederick, Lewitzki Victor, Löhr Mario, Blum Robert, Herud Petra, Flentje Michael, Monoranu Camelia-Maria
Department of Radiation Oncology, University of Würzburg, Würzburg, Germany.
Department of Radiation Oncology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany.
Cancer Cell Int. 2022 Feb 19;22(1):87. doi: 10.1186/s12935-022-02510-4.
Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. However, there is no established marker to identify these stem cells.
Paired samples from glioma patients were analyzed by immunohistochemistry for expression of the following stem cell markers: CD133, Musashi, Nanog, Nestin, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (Sox2). In addition, the expression of osteopontin (OPN) was investigated. The relative number of positively stained cells was determined. By means of Kaplan-Meier analysis, a possible association with overall survival by marker expression was investigated.
Sixty tissue samples from 30 patients (17 male, 13 female) were available for analysis. For Nestin, Musashi and OPN a significant increase was seen. There was also an increase (not significant) for CD133 and Oct4. Patients with mutated Isocitrate Dehydrogenase-1/2 (IDH-1/2) status had a reduced expression for CD133 and Nestin in their recurrent tumors. Significant correlations were seen for CD133 and Nanog between OPN in the primary and recurrent tumor and between CD133 and Nestin in recurrent tumors. By confocal imaging we could demonstrate a co-expression of CD133 and Nestin within recurrent glioma cells. Patients with high CD133 expression had a worse prognosis (22.6 vs 41.1 months, p = 0.013). A similar trend was seen for elevated Nestin levels (24.9 vs 41.1 months, p = 0.08).
Most of the evaluated markers showed an increased expression in their recurrent tumor. CD133 and Nestin were associated with survival and are candidate markers for further clinical investigation.
尽管采用了多模式方法，但胶质母细胞瘤的复发仍难以预防。这可能部分归因于所谓的胶质瘤干细胞。然而，目前尚无用于识别这些干细胞的成熟标志物。
采用免疫组织化学方法分析胶质瘤患者的配对样本，以检测以下干细胞标志物的表达：CD133、Musashi、Nanog、巢蛋白（Nestin）、八聚体结合转录因子4（Oct4）和性别决定区Y盒2（Sox2）。此外，还研究了骨桥蛋白（OPN）的表达。测定阳性染色细胞的相对数量。通过Kaplan-Meier分析，研究标志物表达与总生存期之间的可能关联。
来自30例患者（17例男性，13例女性）的60份组织样本可供分析。巢蛋白、Musashi和OPN的表达显著增加。CD133和Oct4也有增加（不显著）。异柠檬酸脱氢酶-1/2（IDH-1/2）突变状态的患者在复发肿瘤中CD133和巢蛋白的表达降低。在原发性肿瘤和复发性肿瘤中，OPN与CD133和Nanog之间以及复发性肿瘤中CD133和巢蛋白之间存在显著相关性。通过共聚焦成像，我们可以证明复发性胶质瘤细胞中CD133和巢蛋白的共表达。CD133高表达的患者预后较差（22.6个月对41.1个月，p = 0.013）。巢蛋白水平升高也有类似趋势（24.9个月对41.1个月，p = 0.08）。
大多数评估的标志物在复发性肿瘤中表达增加。CD133和巢蛋白与生存期相关，是进一步临床研究的候选标志物。
