4.6 Article

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

Journal

JOURNAL OF NEUROSURGERY
Volume 129, Issue 6, Pages 1429-1437

Publisher

AMER ASSOC NEUROLOGICAL SURGEONS
DOI: 10.3171/2017.6.JNS17562

Keywords

clival chordomas; degree of resection; classification; radiotherapy; PDGFR-beta; invasion; prognosis; oncology

Funding

  1. Research Special Fund for Public Welfare Industry of Health [201402008]
  2. National High Technology Research and Development Program of China (863 Program) [2014AA020610]
  3. National Natural Science Foundation of China [81271522]
  4. Innovation Foundation of Beijing Neurosurgical Institute [Youth-2014008]

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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-beta (PDGFR-beta) 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-beta expression were significantly longer than those of patients with higher PDGFR-beta expression. Reduction of PDGFR-beta suppressed the invasion ability of cells in vitro. In addition, reduction of PDGFR-beta 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-beta expression level are valuable prognostic factors in patients with clival chordomas. PDGFR-beta could regulate invasion through the mTOR pathway in clival chordoma cells.

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