Ko Eun-A, Lee Haeyeong, Sanders Kenton M, Koh Sang Don, Zhou Tong
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA.
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA.
Transl Oncol. 2020 Feb;13(2):233-240. doi: 10.1016/j.tranon.2019.10.002. Epub 2019 Dec 21.
Alpha-type platelet-derived growth factor receptor (PDGFRα) is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. PDGFRα plays an important role in the regulation of several biological processes and contributes to the pathophysiology of a broad range of human cancers, including glioma. Here, we hypothesize that the genes directly or indirectly influenced by PDGFRα might be useful for prognosis in glioma.
By comparing the genome-wide gene expression pattern between PDGFRα and PDGFRα cells from human oligodendrocyte progenitor, we defined the genes potentially influenced by PDGFRα.
The PDGFRα-influenced genes are strongly associated with cancer-related pathways. We subsequently developed a prognostic gene signature derived from the PDGFRα-influenced genes. This gene signature is able to predict clinical outcome of glioma. This signature is also independent of traditional prognostic factors of glioma. Resampling tests indicate that the prognostic power of this gene signature outperforms random gene sets selected from human genome. More importantly, this signature is superior to the random gene signatures selected from glioma related genes.
Despite the absence of clear elucidation of molecular mechanisms, this study suggests the vital role of PDGFRα in carcinogenesis. Furthermore, the PDGFRα-based gene signature provides a promising prognostic tool for glioma and validates PDGFRα as a novel and effective therapeutic target in human cancers.
α型血小板衍生生长因子受体（PDGFRα）是血小板衍生生长因子家族成员的细胞表面酪氨酸激酶受体。PDGFRα在多种生物学过程的调节中发挥重要作用，并参与包括胶质瘤在内的多种人类癌症的病理生理过程。在此，我们假设受PDGFRα直接或间接影响的基因可能对胶质瘤的预后有用。
通过比较来自人少突胶质前体细胞的PDGFRα阳性和阴性细胞之间的全基因组基因表达模式，我们确定了可能受PDGFRα影响的基因。
受PDGFRα影响的基因与癌症相关通路密切相关。随后，我们从受PDGFRα影响的基因中开发了一种预后基因特征。这种基因特征能够预测胶质瘤的临床结局。该特征也独立于胶质瘤的传统预后因素。重采样测试表明，这种基因特征的预后能力优于从人类基因组中随机选择的基因集。更重要的是，该特征优于从胶质瘤相关基因中随机选择的基因特征。
尽管分子机制尚未明确阐明，但本研究表明PDGFRα在致癌过程中起着至关重要的作用。此外，基于PDGFRα的基因特征为胶质瘤提供了一种有前景的预后工具，并验证了PDGFRα作为人类癌症中一种新的有效治疗靶点的作用。
