Proteomics Analysis Identified ASNS as a Novel Biomarker for Predicting Recurrence of Skull Base Chordoma

Yutao Shen; Mingxuan Li; Yujia Xiong; Songbai Gui; Jiwei Bai; Yazhuo Zhang; Chuzhong Li

doi:10.3389/fonc.2021.698497

Proteomics Analysis Identified ASNS as a Novel Biomarker for Predicting Recurrence of Skull Base Chordoma

Front Oncol. 2021 Sep 1:11:698497. doi: 10.3389/fonc.2021.698497. eCollection 2021.

Authors

Yutao Shen^{1

2}, Mingxuan Li^{1

2}, Yujia Xiong^{1

2}, Songbai Gui¹, Jiwei Bai¹, Yazhuo Zhang^{1

2

3

4}, Chuzhong Li^{1

2}

Affiliations

¹ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
³ Center of Brain Tumor, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
⁴ China National Clinical Research Center for Neurological Diseases, Beijing, China.

Abstract

Background: 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.

Method: Using 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.

Results: Among 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.

Conclusion: This 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.

Keywords: asparagine synthetase; nomogram; proteomics; recurrence; skull base chordoma.