Abstract
SOX2 copy number and mRNA expression were analysed to examine the clinical significance of SOX2 activation in HNSCC. Gene expression signatures reflecting SOX2 activation were identified in an HNSCC cohort. Patients with HNSCC were classified into two subgroups according to the gene expression signature: SOX2-high and SOX2-low. The clinical significance of SOX2 activation was further validated in two independent cohorts. Moreover, clinical significance of SOX2 activation in response to radiotherapy was assessed in patients with HNSCC. The relationship between SOX2 activation and radiotherapy was validated in an in vitro experiment. Patients in the SOX2-high subgroup had a better prognosis than patients in the SOX2-low subgroup in all three patient cohorts. Results of multivariate regression analysis showed that SOX2 signature was an independent predictor of the overall survival of patients with HNSCC (hazard ratio, 1.45; 95% confidence interval, 1.09–1.92; P = 0.01). Interestingly, SOX2 activation was a predictor of therapy outcomes in patients receiving radiotherapy. Moreover, SOX2 overexpression enhanced the effect of radiotherapy in HNSCC cell lines. SOX2 activation is associated with improved prognosis of patients with HNSCC and might be used to predict which patients might benefit from radiotherapy.
Highlights
Head and neck squamous cell carcinoma (HNSCC) most commonly arises from the mucosa of the oral cavity, pharynx, and larynx, and is the sixth most common cancer worldwide, with an incidence rate of approximately 600,000 patients per year[1]
We found that Sex determining region Y-box 2 gene (SOX2) signature is a predictor of HNSCC prognosis
We observed that SOX2 signature could predict patient outcomes with RT, suggesting that SOX2 signature provides novel information for developing new biomarkers to assist in clinical decision making
Summary
Head and neck squamous cell carcinoma (HNSCC) most commonly arises from the mucosa of the oral cavity, pharynx, and larynx, and is the sixth most common cancer worldwide, with an incidence rate of approximately 600,000 patients per year[1]. Several studies have indicated that SOX2 is associated with the development of various malignant tumours, including glioblastoma, small-cell lung cancer, and different types of squamous cell carcinomas (SCCs)[6,7,8,9]. Some studies indicate that SOX2 expression promotes the invasiveness of HNSCC cells and that high SOX2 protein levels are closely associated with poor prognosis of patients with HNSCC10–12. Züllig et al reported that low SOX2 expression is significantly associated with the poor survival of patients with HNSCC13. Additional studies are required to validate the role of SOX2 in HNSCC and to determine treatment approaches for HNSCC patients. We systematically characterised genomic data of patients with HNSCC to determine the molecular subtypes associated with SOX2 activation and prognosis of patients with HNSCC. We investigated the clinical relevance of SOX2 activation in response to radiotherapy (RT) in patients with HNSCC
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