Analysis of clinical factors and PDGFR-β in predicting prognosis of patients with clival chordoma

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OBJECTIVE

In 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.

METHODS

A 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.

RESULTS

According 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.

CONCLUSIONS

Extent 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.

ABBREVIATIONS GTR = gross-total resection; KPS = Karnofsky Performance Scale; mTOR = mammalian target of rapamycin; NTR = non–total resection; OS = overall survival; PDGFR-β = platelet-derived growth factor receptor–β; PFS = progression-free survival; PR = partial resection; siRNA = small interfering RNA; STR = subtotal resection; TMA = tissue microarray.

Article Information

Correspondence Yazhuo Zhang: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. zyz2004520@yeah.net.

INCLUDE WHEN CITING Published online January 5, 2018; DOI: 10.3171/2017.6.JNS17562.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Kaplan-Meier survival functions. A and B: GTR was associated with longer patient OS (A) and PFS (B). C and D: Type I tumors were associated with longer patient OS (C) and PFS (D).

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    Kaplan-Meier survival functions. A and B: The median OS (A) and PFS (B) for patients with primary tumors were significantly longer than those for patients with recurrence. C: The median OS of patients who underwent radiotherapy was significantly longer than that of patients who did not undergo radiotherapy. D: There was no difference in median PFS time between patients with radiotherapy and those without radiotherapy.

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    A: Group A, HScore = 1.25. B: Group B, HScore = 88.15. C: Group C, HScore = 205.57. D and E: In the GTR group, there was no significant difference between the 3 groups in terms of PFS (D) or OS (E). F and G: In the NTR group, the PFS (F) and OS (G) for HScore group A were significantly longer than those of HScore groups B and C. Figure is available in color online only.

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    A: Western blotting analysis showing that expression of PDGFR-β and phospho-PDGFR-β (pPDGFR-β) was significantly suppressed by Si-A and Si-C. B: Polymerase chain reaction analysis revealed that the PDGFR-β mRNA level was significantly suppressed by Si-A and Si-C. *p < 0.05.

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    Transwell assaying. The invasive cells in group Si-A and group Si-C were significantly decreased compared with those in the control group. A: Control. B: Nonsilence. C: Si-A. D: Si-C. The small round background circles are holes in the membranes of transwell chambers. The invasive cells stained dark; only the single stained cells were counted. E: The invasive cells in the Si-A and Si-C groups decreased significantly to 29% (p = 0.026) and 44% (p = 0.040) compared with those in the control group. *p < 0.05. Figure is available in color online only.

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    PDGFR-β silencing regulates the mTOR pathway. A: Western blot analysis of mTOR and phospho-mTOR (pmTOR) in U-CH2 cells. B: The Western blot analysis reveals a significant reduction of mTOR and phospho-mTOR in the Si-A and Si-C groups compared with those in the control group. *p < 0.05.

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