Differential Proteomic Profiling of Chordomas and Analysis of Prognostic Factors

Background: The recurrence rate of chordoma is high, and the prognosis is poor.

Methods: Differential proteomic analysis was performed on chordomas and adjacent normal tissues, with verification by Western blot. Protein expression was evaluated by immunohistochemistry of 37 chordomas. Association of candidate protein expression with clinical parameters, disease-free survival, and overall survival were analyzed.

Results: We identified 14 up-regulated and 5 down-regulated proteins in chordomas. Expression of alpha enolase (ENO1), pyruvate kinase M2 (PKM2), and gp96 was higher in recurrences than in primary tumors. Univariate analysis showed that significantly adverse factors for disease-free survival were overexpression of ENO1 and PKM2, involvement of contiguous vertebral levels, and inadequate surgical margin at initial surgery. Inadequate surgical margin without radiotherapy, involvement of contiguous vertebral levels, and cervical spine location were adverse factors for overall survival. By multivariate analysis, independent adverse prognostic factors were inadequate surgical margin and involvement of multiple contiguous vertebral levels for recurrence; upper cervical spine location and involvement of contiguous vertebral levels for tumor-related death. Multivariate analysis failed to show the significance of the proteins.

Conclusions: Involvements of multiple contiguous vertebral levels and upper cervical spine, rather than overexpression of ENO1, PKM2, or gp96, are independent prognostic indicators for chordomas.