Development of a prognostic pyroptosis-related gene signature for head and neck squamous cell carcinoma patient

Abstract

Objective Head and neck squamous cell carcinoma (HNSCC) is a major threat to public health. Pyroptosis is a form of inflammatory programmed cell death that is still incompletely understood. The role of pyroptotic cell death in HNSCC remains to be fully defined. As such, the present study was developed to explore the potential prognostic utility of a pyroptosis-related gene (PRG) signature in HNSCC. Methods PRG expression patterns and the associated mutational landscape in HNSCC were analyzed, after which a 6-gene prognostic model was constructed through least absolute shrinkage and selection operator (LASSO) and Cox regression analyses using the TCGA dataset, followed by validation with two GEO datasets (GSE41643 and GSE65858). The relative expression of the genes in the prognostic model was assessed via RT-qPCR in tumor and paired adjacent normal tissue samples from a 32-patient cohort. Potential predictors of patient outcomes associated with this 6-gene model were identified through topological degree analyses of a protein–protein interaction network. Moreover, the prognostic value of NLRP3 as a predictor of HNSCC patient prognosis was established through immunohistochemical (IHC) analyses of samples from 176 HNSCC patients. Lastly, in vitro studies were performed to further demonstrate the relevance of NLRP3 in the context of HNSCC development. Results Differentially expressed PRGs were able to readily differentiate between HNSCC tumors and normal tissues. Risk scores derived from the 6-gene PRG model were independent predictors of HNSCC patient prognosis, and genes that were differentially expressed between low- and high-risk groups were associated with tumor immunity. RT-qPCR assays also showed the potential protective role of NLRP3 in HNSCC patients. IHC analyses further supported the value of NLRP3 as a predictor of HNSCC patient outcomes. Invasion and migration assays demonstrated the potential role of NLRP3 in the inhibition of HNSCC development. Conclusions Overall, these results highlight a novel prognostic gene signature that offers value in the context of HNSCC patient evaluation, although additional research will be essential to elucidate the mechanisms linking these PRGs to HNSCC outcomes.

Identification and validation of a prognostic signature of autophagy, apoptosis and pyroptosis-related genes for head and neck squamous cell carcinoma: to imply therapeutic choices of HPV negative patients

“…However, these models were based on certain cell death type and obtained limited predictive potentials. Consistent with our study, ATG5 and PRKN were identified as risk genes ( 27 , 29 , 30 ), whereas, CDKN2A and NLRP1 predicted favorable survivals of HNSCC ( 28 – 33 ). Together, the combined index, CDI, supplied a more promising efficacy for the prognosis of HNSCC.…”

“…Remarkably, the combined index, CDI, demonstrated a significantly improved prognostic value compared with the single type indices. There are several studies reported prognostic models based on cell death related genes ( 27 – 33 ). However, these models were based on certain cell death type and obtained limited predictive potentials.…”

Identification of new head and neck squamous cell carcinoma subtypes and development of a novel score system (PGSscore) based on variations in pathway activity between tumor and adjacent non-tumor samples

“…11 G–I). Finally, we compared the 1-year AUC value of the nomogram developed based on the PGSscore with that of other existing signatures [14] , [41] , [42] , [43] , [44] , [45] , [46] , indicating that our nomogram had higher predictive accuracy than individual signatures ( Fig. 11 J).…”

Developing a pyroptosis-related gene signature to better predict the prognosis and immune status of patients with head and neck squamous cell carcinoma

“…In particular, the large number of bacteria and viruses in the oral cavity, pharynx, and larynx can increase the chance of infection, along with the occurrence of pyroptosis. Although pyroptosis-related genes (PRGs) have prognostic value in predicting the outcomes of HNSCC patients ( Shen et al, 2021 ; Zhu et al, 2022 ), PRGs-mediated immune infiltration and drug sensitivity are unclear.…”