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

Shen, Ya Ching; Li, Xinyu; Wang, De Ming; Zhang, Liming; Li, Xiao; Xia, Tong; Shang, Xunjie; Yang, Xitao; Su, Lixin; Fan, Xindong

doi:10.1016/j.tranon.2021.101233

Cited by 25 publications

(34 citation statements)

References 36 publications

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“…In line with these reports, the results of our PPI network and survival analyses suggested that NLRP3 may be a valuable predictor of prognosis among HNSCC patients. Relative to another similar study [ 26 ], we developed a distinct PRG-based prognostic model and highlighted the potential role of NLRP3 as a predictor of HNSCC patient outcomes, while finding that lower levels of NLRP3 expression detected via IHC staining were associated with a worse prognosis. In vitro studies of invasion and migration activity also underscored the protective role of NLRP3 in the inhibition of HNSCC development.…”

Section: Discussionmentioning

confidence: 96%

“…Treatment with TPL can activate GSDME-mediated pyroptosis by inhibiting the expression of HK-II in the mitochondria in HNSCC [ 25 ]. Although PRGs have been shown to have the prognostic value when predicting HNSCC patient outcomes [ 26 ], PRG-mediated immune infiltration and the aberrant changes in the biological behavior of cancer cells remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…In the present study, we established an improved PR gene set which composed of four major segments. First, several researchers used the same PR gene set containing 33 members to probe into the roles of PRGs in cancers ( Shen et al, 2021 ; Lin et al, 2021 ; Ye et al, 2021 ). These PRGs were also adopted in our study.…”

Section: Methodsmentioning

confidence: 99%

Pyroptosis-Related Risk Signature Exhibits Distinct Prognostic, Immune, and Therapeutic Landscapes in Hepatocellular Carcinoma

Zhao

Song²,

et al. 2022

Front. Genet.

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Background: Hepatocellular carcinoma (HCC) is a common abdominal cancer. The existing therapeutic approaches often fail to achieve satisfactory results. Pyroptosis, an inflammatory form of programmed cell death, provides new ideas for anticancer treatment. However, the roles of pyroptosis-related (PR) genes (PRGs) in HCC remain elusive.Methods: Differentially expressed genes (DEGs) (n = 22) were screened out using TCGA and GTEx databases. A novel PR risk signature was constructed through Lasso regression analysis. Its prognostic value was evaluated through a series of survival analyses and was tested in ICGC and GSE14520 cohorts. CIBERSORT, ssGSEA, and ESTIMATE methods were employed to determine the effects of the PR risk score on the tumor immune microenvironment (TIM). The TIDE scoring system, IMvigor210 cohort, GSE109211 dataset, and GSDC database were applied to explore the associations of the PR risk score with therapeutic effects. The biofunctions of WNK1 in hepatocellular cancer (HC) cells were confirmed through qPCR, colony formation, and Transwell assays.Results: Overall, 22 of 45 PRGs (48.9%) were abnormally expressed in HCC samples. Then, a PR risk signature consisting of eight PRGs was constructed. A high PR risk score led to an unfavorable prognosis. The PR risk score was identified as an independent prognostic factor of HCC and could increase the decision-making benefit of the traditional TNM model. In addition, we established a nomogram containing the clinical stage and PR risk score to predict the survival rates of HCC patients. The prognostic value of the PR model was successfully validated in ICGC and GSE14520 cohorts. Moreover, high PR risk conferred the decreased infiltration level of CD8+ T cells and weakened the activities of “cytolytic activity” pathways. As for therapeutic correlation, a high PR risk score seemed to imply a poor efficacy of PD-1/L1 inhibitors and sorafenib. Finally, the overexpression of WNK1 could promote the proliferation, migration, and invasion of HC cells.Conclusions: The PR risk score was closely related to the prognosis, antitumor immune process, therapeutic outcomes, and malignant progression of HCC. WNK1, the core regulator of pyroptosis, possesses pro-oncogenic abilities, showing promise as a novel treatment target.

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“…Head and neck squamous carcinoma is one of the more common malignancies worldwide, with 550,000 new cases and about 380,000 deaths per year [16,17] . It is not only aggressive and lethal, but also causes serious facial deformities, speech, chewing and swallowing dysfunctions as well as psychosocial problems to patients.…”

Section: Discussionmentioning

confidence: 99%

“…Further, the analysis of immune cell in ltration in both groups of patients revealed a positive correlation between the macrophages and risk scores. This phenomenon was associated with the fact that macrophages are essential in the HNSCCC microenvironment for the regulation of the in ammatory reactions [17] . It was hence suggested that the model may serve as a predictor of increased immune cell in ltration.…”

Section: Discussionmentioning

confidence: 99%

Nonnegative Matrix Factorization Model-Based Construction For Molecular Clustering and Prognostic Assessment of Squamous Carcinoma of Head and Neck

Li¹,

Yang²

2021

Preprint

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Purpose: Exploring nonnegative matrix factorization (NMF) model-based clustering and prognostic modeling of head and neck squamous carcinoma (HNSCC). Methods: The transcriptome microarray data of HNSCC samples were downloaded from The Cancer Genome Atlas (TCGA) and Shanghai Ninth People’s Hospital, and NMF clustering was constructed using the R software package. Relevant prognostic models were developed based on clustering. Results: Based on NMF, all samples were divided into 2 subgroups. Predictive models were constructed by analysing the differential gene between the two subgroups. Results of survival analysis in the current study revealed that the high-risk group had a poor prognosis. Further, results of multi-factor Cox regression analysis revealed that the predictive model was an independent predictor of prognosis. Conclusion: It was evident that the NMF-based prognostic model is a useful guide to the prognostic assessment of HNSCC.

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

Abstract: Highlights Pyroptosis genes were differentially expressed between HNSCC and normal tissue. Developed a model for prognostic prediction of HNSCC based on pyroptosis genes. The risk-score model was proved to be promising and reliable in practical patients.

Cited by 25 publications

References 36 publications

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

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

Pyroptosis-Related Risk Signature Exhibits Distinct Prognostic, Immune, and Therapeutic Landscapes in Hepatocellular Carcinoma

Nonnegative Matrix Factorization Model-Based Construction For Molecular Clustering and Prognostic Assessment of Squamous Carcinoma of Head and Neck

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