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Novel prognostic model established for patients with head and neck squamous cell carcinoma based on pyroptosis-related genes.

ABSTRACT: We aimed at establishing a risk - score model using pyroptosis-related genes to predict the prognosis of patients with head and neck squamous cell carcinoma (HNSCC). A total of 33 pyroptosis-related genes were selected. We then evaluated the data of 502 HNSCC patients and 44 normal patients from TCGA database. Gene expression was then profiled to detect differentially expressed genes (DEGs). Using the univariate, the least absolute shrinkage and selection operator (LASSO) Cox regression analyses, we generated a risk - score model. Tissue samples from neoplastic and normal sites of 44 HNSCC patients were collected. qRT-PCR were employed to analyze the mRNA level of the samples. Kaplan-Meier method was used to evaluate the overall survival rate (OS). Enrichment analysis was performed to elucidate the underlying mechanism of HNSCC patient's differentially survival status from the perspective of tumor immunology. 17 genes were categorized as DEGs. GSDME, IL-6, CASP8, CASP6, NLRP1 and NLRP6 were used to establish the risk - score model. Each patient's risk score in the TCGA cohort was calculated using the risk - score formula. The risk score was able to independently predict the OS of the HNSCC patients (P = 0.02). The OS analysis showed that the risk score model (P < 0.0001) was more reliable than single gene, a phenomenon verified by practical patient cohort. Additionally, enrichment analysis indicated more active immune activities in low-risk group than high-risk group. In conclusion, our risk - score model has provided novel strategy for the prediction of HNSCC patients' prognosis.

SUBMITTER: Shen Y

PROVIDER: S-EPMC8487076 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is a life-threatening disease with poor prognosis. Pyroptosis has been recently disclosed as a programmed cell death triggered by invasive infection, involved in cancer development. However, the prognosis role of pyroptosis-related genes in HNSCC has not been discussed.MethodsThe RNA sequence data of pyroptosis-related genes were obtained from The Cancer Genome Atlas (TCGA) database. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were performed to screen the HNSCC survival-related signature genes. We established a HNSCC risk model with the identified prognostic genes, then divided the HNSCC patients into low- and high-risk subgroups according to median risk score. Moreover, we utilized Gene Expression Omnibus (GEO) dataset to validate the risk model. Go and KEGG analyses were conducted to reveal the potential function of differential expression of genes that identified between low- and high-risk subgroups. ESTIMATE algorithm was performed to investigate the immune infiltration of tumors. Correlation between signature gene expression and drug-sensitivity was disclosed by Spearman's analysis.ResultsWe constructed a HNSCC risk model with identified seven pyroptosis-related genes (CASP1, GSDME, IL6, NLRP1, NLRP2, NLRP6, and NOD2) as prognostic signature genes. High-risk subgroup of HNSCC patients in TCGA cohort correlated with lower survival probability than patients from low-risk subgroup (p < .001), and the result is verified with GEO dataset. In addition, 161 genes were identified differentially expressed between the low- and high-risk subgroups in the TCGA cohort, mainly related to immune response. Higher PD-L1 expression level was found in the high-risk subgroup that indicated the possible employment of immune checkpoint inhibitors. IL6 was positively correlated with WZ3105 and MPS-1-IN-1 in the cancer therapeutics response portal database.ConclusionWe built and verified a risk model for HNSCC prognosis using seven pyroptosis-related signature genes, which could predict the overall survival of HNSCC patients and facilitate treatment.

Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous malignant cancer with poor prognosis. Pyroptosis is defined as a novel inflammation-dependent programmed cell death. However, the pyroptosis-associated gene expression in HNSCC and their relationship with prognosis are still indistinct.Material and methodsWe acquired the mRNA expression information of HNSCC patients from publicly available TCGA and GEO databases. We compared the tumor issues and adjacent normal tissues in terms of the gene expression for the purpose of identifying differentially expressed genes (DEGs). Based on these genes, we established a risk signature by the LASSO Cox regression in the TCGA cohort and validated the results in a GEO cohort. We also verified the levels of relevant mRNA expression in the model by RT-qPCR analysis. Eventually, functional enrichment approach was carried out to explore the potential mechanisms.ResultsOur team found a total of 18 differentially expressed genes (DEGs) between the HNSCC and healthy samples, and 4 DEGs displayed a remarkable association with the overall survival (OS) (P < 0.05). A 4-gene signature was constructed, presenting beneficial forecast power in both TCGA and GEO cohorts. Our team categorized patients into a group with high risk and another group with low risk as per the average risk value of the 4-gene feature. The individuals in the low risk group displayed a notably greater OS compared with the high risk one (P < 0.01). The Cox regression study demonstrated the independent forecast capability of the risk score. The receiver operating characteristic approach facilitated the verification of the forecast function of the gene signature. Posterior to verification, 4 genes were aberrantly expressed in the HNSCC and healthy samples. Functional study displayed that these groups presented diverse immunity conditions.ConclusionPyroptosis-associated genes are pivotal for the prognosis of HNSCC and can serve as potential therapeutic targets.

Project description:ObjectiveHead 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.MethodsPRG 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.ResultsDifferentially 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.ConclusionsOverall, 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.

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Novel prognostic model established for patients with head and neck squamous cell carcinoma based on pyroptosis-related genes.

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