Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma

SIMPLE SUMMARY: This study aimed to explore the relationship between necroptosis and oral squamous cell carcinoma (OSCC) preliminarily, and search for the novel prognostic factors for OSCC, in order to help guide the mechanism exploration, clinical diagnosis, targeted therapy, and prognosis of OSCC patients. The prognostic signature of necroptosis-related genes (NRGs) for OSCC has been constructed through relevant bioinformatics methods, which showed that HPRT1 can serve as a novel independent prognostic factor for OSCC. The experiments also validated that the knockdown of HPRT1 could suppress the proliferation and migration of OSCC cells. Furthermore, the relationship between necroptosis and OSCC has also been discussed, which suggests that necroptosis might promote the development and metastasis of OSCC by initiating inflammatory response and immunosuppression. ABSTRACT: The dual role of necroptosis in inhibiting and promoting tumor development has gradually received much attention because of its essential significance for targeted treatment. Accordingly, this study aims to explore the relationship between necroptosis and oral squamous cell carcinoma (OSCC), and search for novel prognostic factors for OSCC. RNA-seq data and clinical information were downloaded from TCGA and GTEx databases. The prognostic signature of necroptosis-related genes (NRGs) was constructed by univariate Cox regression analysis and the LASSO Cox regression model. Moreover, survival analyses, ROC curves, and nomograms were adopted to further analyze. GO and KEGG analyses and immune infiltration analyses were used for function enrichment and immune feature research in turn. The NRG prognostic signature expression was higher in OSCC tissues than in normal tissues, and the overall survival (OS) rate of the high-expression group was much lower. HPRT1 was proved to be an independent prognostic factor in OSCC. Furthermore, the function enrichment analyses revealed that NRGs were involved in necroptosis, apoptosis, inflammation, and immune reaction. The expression of NRGs was related to immunosuppression in OSCC. Furthermore, the knockdown of HPRT1 could suppress the proliferation and migration of OSCC. In conclusion, the high expression of NRG prognostic signature is associated with poor prognosis in OSCC, and HPRT1 can serve as a novel independent prognostic factor for OSCC.