Platelet-derived growth factor receptor α/glial fibrillary acidic protein expressing peritumoral astrocytes associate with shorter median overall survival in glioblastoma patients.,Glia

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Platelet-derived growth factor receptor α/glial fibrillary acidic protein expressing peritumoral astrocytes associate with shorter median overall survival in glioblastoma patients.
Glia ( IF 5.4 ) Pub Date : 2019-11-26 , DOI: 10.1002/glia.23756
Lina Leiss ₁ , Alessandro Mega ₁ , Thomas Olsson Bontell _{2,

3} , Monica Nistér ₁ , Anja Smits _{4,

5} , Sara Corvigno _{1,

6} , Mohummad Aminur Rahman ₇ , Per Øyvind Enger _{7,

8} , Hrvoje Miletic _{7,

9} , Arne Östman ₁

Affiliation

The microenvironment and architecture of peritumoral tissue have been suggested to affect permissiveness for infiltration of malignant cells. Astrocytes constitute a heterogeneous population of cells and have been linked to proliferation, migration, and drug sensitivity of glioblastoma (GBM) cells. Through double-immunohistochemical staining for platelet-derived growth factor receptor α (PDGFRα) and glial fibrillary acidic protein (GFAP), this study explored the intercase variability among 45 human GBM samples regarding density of GFAP+ peritumoral astrocytes and a subset of GFAP+ peritumoral astrocyte-like cells also expressing PDGFRα. Large intercase variability regarding the total peritumoral astrocyte density and the density of PDGFRα+/GFAP+ peritumoral astrocyte-like cells was detected. DNA fluorescence in situ hybridization analyses for commonly altered genetic tumor markers supported the interpretation that these cells represented a genetically unaffected host cell subset referred to as PDGFRα+/GFAP+ peritumoral astrocytes. The presence of PDGFRα+/GFAP+ peritumoral astrocytes was significantly positively correlated to older patient age and peritumoral astrocyte density, but not to other established prognostic factors. Notably, presence of PDGFRα+/GFAP+ peritumoral astrocytes, but not peritumoral astrocyte density, was associated with significantly shorter patient overall survival. The prognostic association of PDGFRα+/GFAP+ peritumoral astrocytes was confirmed in multivariable analyses. This exploratory study thus demonstrates previously unrecognized intercase variability and prognostic significance of peritumoral abundance of a novel PDGFRα+ subset of GFAP+ astrocytes. Findings suggest clinically relevant roles of the microenvironment of peritumoral GBM tissue and encourage further characterization of the novel astrocyte subset with regard to origin, function, and potential as biomarker and drug target.

中文翻译：

胶质母细胞瘤患者中表达血小板衍生的生长因子受体α/神经胶质纤维酸性蛋白与肿瘤周围星形胶质细胞的中位总生存期较短有关。

肿瘤周围组织的微环境和结构被认为会影响恶性细胞浸润的容忍度。星形胶质细胞构成异质性细胞群，并与胶质母细胞瘤（GBM）细胞的增殖，迁移和药物敏感性有关。通过对血小板源性生长因子受体α（PDGFRα）和神经胶质原纤维酸性蛋白（GFAP）的双重免疫组织化学染色，本研究探讨了45例人GBM样品中GFAP +肿瘤周围星形胶质细胞和部分GFAP +肿瘤周围星形胶质细胞-密度的病例间变异性。像也表达PDGFRα的细胞。关于总的肿瘤周围星形胶质细胞密度和PDGFRα+ / GFAP +肿瘤周围星形胶质样细胞的密度，发现大的病例间差异。对常见改变的遗传肿瘤标志物的DNA荧光原位杂交分析支持以下解释：这些细胞代表了遗传上未受影响的宿主细胞亚群，称为PDGFRα+ / GFAP +肿瘤周围星形胶质细胞。PDGFRα+ / GFAP +肿瘤周围星形胶质细胞的存在与年龄较大的患者年龄和肿瘤周围星形胶质细胞密度显着正相关，但与其他已确定的预后因素无显着正相关。值得注意的是，PDGFRα+ / GFAP +肿瘤周围星形胶质细胞的存在，而不是肿瘤周围星形胶质细胞的密度，与患者总体生存期明显缩短有关。在多变量分析中证实了PDGFRα+ / GFAP +肿瘤周围星形胶质细胞的预后关联。因此，该探索性研究证明了先前无法识别的跨细胞变异性和GFAP +星状细胞的新型PDGFRα+子集的肿瘤周围丰度的预后意义。研究结果表明，肿瘤周围GBM组织微环境在临床上具有重要的作用，并在起源，功能以及作为生物标志物和药物靶标的潜力方面，鼓励进一步表征新的星形胶质细胞亚群。

更新日期：2019-11-27

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