Abstract
BackgroundThe prognostic factors of skull base chordoma associated with outcomes of patients after surgery remain inadequately identified. This study was designed to identify a novel prognostic factor for patients with skull base chordoma.MethodUsing a proteomic technique, the tumor biomarkers that were upregulated in the rapid-recurrence group of chordoma were screened and then narrowed down by bioinformatic analysis. Finally one potential biomarker was chosen for validation by immunohistochemistry using tissue microarray (TMA). A total of 187 patients included in TMA were randomly divided into two cohorts, the training cohort included 93 patients and the validation cohort included 94 patients. Kaplan-Meier survival analysis was used to assess the patients’ survival. Univariable and multivariable Cox regression analysis were used to identify prognostic factors predicting recurrence-free survival (RFS). CCK-8 assay, clonal formation assay and transwell assay were used to test the effect of asparagine synthetase (ASNS) on the proliferation, migration and invasion in chordoma cell lines.ResultsAmong 146 upregulated proteins, ASNS was chosen as a potential prognostic biomarker after bioinformatics analysis. The H-scores of ASNS ranged from 106.27 to 239.58 in TMA. High expression of ASNS was correlated with shorter RFS in both the training cohort (p = 0.0093) and validation cohort (p < 0.001). Knockdown of ASNS by small interfering RNA (siRNA) inhibited the growth, colony formation, migration and invasion of chordoma cells in vitro.ConclusionThis study indicates that high expression of ASNS is correlated with poor prognosis of patients with skull base chordoma. ASNS may be a useful prognostic factor for patients with skull base chordoma.
Highlights
Chordoma, a rare low-grade malignant tumor that comprises 14% of primary bone tumors, arises in the axial bones, and as much as 35% of chordoma locates in the clivus region [1]
To identify proteins that were differentially expressed in the rapid-recurrence group and slow-recurrence group of skull base chordoma, a tandem mass tag (TMT) mass-spectrometric technique was used. 3667 and 3737 proteins were quantified by each technical replicate, respectively, 4286 proteins were quantified from the two technical replicates and subsequently filtered with manually selected filter exclusion parameters
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that alanine, aspartate and glutamate metabolism was mainly involved in the rapid-recurrence group (Figure 1C and Supplementary Table 2)
Summary
A rare low-grade malignant tumor that comprises 14% of primary bone tumors, arises in the axial bones, and as much as 35% of chordoma locates in the clivus region [1]. Chordoma is generally recognized that originates from notochordal remnants [2]. Chordoma is a slowgrowing and low-grade malignant tumor, effective treatments for curing chordoma are still lacking. Chordoma usually locates close to crucial neurovascular structures, and the tumor can infringe surrounding tissues and vessels, making total resection difficult to accomplish and causing a high recurrence rate. The prognostic factors of skull base chordoma associated with outcomes of patients after surgery remain inadequately identified. This study was designed to identify a novel prognostic factor for patients with skull base chordoma
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