1Beijing Neurosurgical Institute, Capital Medical University; and.
2Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
J Neurosurg. 2018 Dec 1;129(6):1429-1437. doi: 10.3171/2017.6.JNS17562. Epub 2018 Jan 5.
OBJECTIVEIn this study, the authors' aim was to research clinical features and prognostic factors in patients harboring clival chordomas and explore the relationship between platelet-derived growth factor receptor-β (PDGFR-β) expression and tumor invasion and prognosis of clival chordoma.METHODSA total of 242 patients were retrospectively analyzed. Clinical information, including extent of resection, Al-Mefty classification, postoperative complications, and postoperative radiotherapy, was reviewed. Kaplan-Meier analysis was used to estimate survival time. Immunohistochemical analysis, quantitative reverse transcription polymerase chain reaction, and Western blotting were used to measure the expression level of proteins or mRNA. Transwell assaying was performed to measure the invasive ability of the tumor cells.RESULTSAccording to the Al-Mefty classification, there were 37, 112, and 93 type I, II, and III tumors, respectively. Gross-total resection (GTR) was achieved in 86 cases (35.5%), subtotal resection (STR) in 63 cases (26.0%), and partial resection (PR) in 93 cases (38.4%). The 5-year progression-free survival (PFS) and overall survival (OS) rates in the GTR group were significantly higher than those in the non-total resection (NTR; i.e., STR and PR) group (p < 0.001). The 5-year PFS and OS rates for patients with type I tumors were significantly higher than those for patients harboring types II and III tumors (p < 0.001). In the NTR group, the median PFS and OS of patients with lower PDGFR-β expression were significantly longer than those of patients with higher PDGFR-β expression. Reduction of PDGFR-β suppressed the invasion ability of cells in vitro. In addition, reduction of PDGFR-β can obviously downregulate the expression levels of mammalian target of rapamycin (mTOR) or phospho-mTOR.CONCLUSIONSExtent of resection, Al-Mefty classification, primary tumor, postoperative radiotherapy, and PDGFR-β expression level are valuable prognostic factors in patients with clival chordomas. PDGFR-β could regulate invasion through the mTOR pathway in clival chordoma cells.
本研究旨在探讨颅底脊索瘤患者的临床特征和预后因素，并探讨血小板衍生生长因子受体-β（PDGFR-β）表达与颅底脊索瘤侵袭和预后的关系。
回顾性分析 242 例患者的临床资料，包括切除程度、Al-Mefty 分级、术后并发症和术后放疗等。采用 Kaplan-Meier 分析估计生存时间。免疫组织化学分析、定量逆转录聚合酶链反应和 Western blot 用于测量蛋白或 mRNA 的表达水平。Transwell 测定用于测量肿瘤细胞的侵袭能力。
根据 Al-Mefty 分级，Ⅰ型、Ⅱ型和Ⅲ型肿瘤分别为 37、112 和 93 例。86 例（35.5%）达到全切除（GTR），63 例（26.0%）次全切除（STR），93 例（38.4%）部分切除（PR）。GTR 组的 5 年无进展生存率（PFS）和总生存率（OS）明显高于非全切除组（STR 和 PR 组，p<0.001）。Ⅰ型肿瘤患者的 5 年 PFS 和 OS 明显高于Ⅱ型和Ⅲ型肿瘤患者（p<0.001）。在非全切除组中，PDGFR-β 表达较低的患者的中位 PFS 和 OS 明显长于 PDGFR-β 表达较高的患者。PDGFR-β 减少可抑制细胞的体外侵袭能力。此外，PDGFR-β 减少可明显下调哺乳动物雷帕霉素靶蛋白（mTOR）或磷酸化 mTOR 的表达水平。
切除程度、Al-Mefty 分级、原发肿瘤、术后放疗和 PDGFR-β 表达水平是颅底脊索瘤患者有价值的预后因素。PDGFR-β 可通过 mTOR 通路调节颅底脊索瘤细胞的侵袭。
