Background: Head and neck squamous cell carcinoma (HNSC) is an aggressive type of cancer that lacks early detection, and therefore, has a low 5-year survival rate. The spermine synthase (SMS) gene has been shown to be associated with Snyder-Robinson syndrome and poor prognosis of multiple cancers; however, its regulatory role in HNSC has never been investigated. Therefore, we explored the potential predictive value of SMS in HNSC.
Methods: We explored the association between SMS expression and clinicopathological parameters of HNSC patients by using data from The Cancer Genome Atlas datasets (TCGA). The prognostic value of SMS was evaluated using the Kaplan-Meier plotter, Gene Expression Profiling Interactive Analysis (GEPIA) 2 and univariate and multivariate Cox regression analyses. We further used gene set enrichment analysis (GESA) to investigate the potential roles of SMS in HNSC prognosis and Tumor Immunity Estimation Resource 2.0 (TIMER2.0) to analyze the correlation between immune cell infiltration and SMS expression. Finally, starBase was used to screen out prognosis-associated non-coding RNA genes to constructed the competing endogenous RNA (ceRNA) network. Co-expression and survival analyses were used to identify the ceRNA network's effect on HNSC prognosis.
Results: We found that SMS expression was increased in HNSC compared with normal tissues (P<0.05). In addition, SMS expression was associated with tumor grade (P=0.006), N stage (P=0.001), and prognosis. Survival analysis revealed that high expression of SMS showed worse overall survival (OS) (HR =1.4, P=0.01) and worse disease-free survival (DFS) (HR =1.5, P=0.014). Multivariate Cox analysis further supported the prognostic value of SMS in HNSC (HR =1.006636, P=0.0056). GESA showed that SMS was involved in metabolism- and immune-related pathways. The immune infiltration analyses results showed a decrease in the landscape of immune cell infiltration with high SMS expression and SMS deletion in HNSC. Finally, a ceRNA network (SMS/hsa-miR-23b-3p/KTN1-AS1 and VPS9D1-AS axis) was constructed based on the co-expression and survival analyses in HNSC.
Conclusions: Our findings first revealed that SMS functioned as a potential prognostic biomarker and provide insights into the molecular mechanisms of its function in HNSC. The use of SMS may be powerful for determining worse prognosis HNSC patients.
Keywords: Head and neck squamous cell carcinoma (HNSC); bioinformatics analysis; biomarker; prognosis; spermine synthase (SMS).
2022 Annals of Translational Medicine. All rights reserved.