A novel pyroptosis-related signature predicts prognosis and indicates immunotherapy in oral squamous cell carcinoma.

Abstract

Oral squamous cell carcinoma (OSCC) has been recognized as a frequently occurring oral malignant tumor. Pyroptosis plays an extremely important role in the occurrence and development of cancer, but the role of pyroptosis in OSCC remains unclear. OSCC-related data were obtained from the TCGA and GEO databases. A PSscore risk model was constructed through LASSO regression analysis. The GEO database was utilized as the validation set of the model. The "ESTIMATE" and "CIBERSORT" algorithms were utilized to additionally evaluate the relationship between the immune cell score and PSscore. TIDE and IPS algorithms were used to assess patient response to immunotherapy. In addition, Western blot analysis and MTT assay was used to further validate key genes. Comprehensive bioinformatics analysis showed that a low-PSscore had a significant survival advantage, richer immune cell infiltration, more active immune-related pathways, higher TME scores, and lower tumor purity. The results of TIDE and IPS analysis indicated that the high-PSscore group had higher immune escape potential and was less sensitive to immunotherapy. In contrast, the low-PSscore group patients might be more sensitive to PD1 and CTLA4 + PD1 immunotherapy. Univariate and multivariate COX results indicated that PSscore was an independent prognostic factor in OSCC patients. Another important finding is that BAK1 is a potential target of OSCC and is related to the Nod-like receptor signaling pathway. Knockdown of BAK1 can significantly reduce the proliferation of OSCC cells. The PSscore model could be utilized as a powerful prognostic indicator and can help in the development of new immunotherapies.