Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma

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Background Cuproptosis is considered a novel copper‐dependent cell death model. In this study, we established a novel scoring system based on 10 cuproptosis‐related genes (CRGs) to predict the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC). Methods The RNA‐seq data of HNSCC patients were downloaded from the GEO and TCGA databases and were merged into a novel HNSCC cohort. Multiomics landscape analyses were conducted, including tumor mutation burden (TMB), copy number variations and the interaction network of CRGs. Patients were then divided into different cuproptosis subtypes based on the expression of 10 CRGs and subsequently regrouped into novel gene clusters referring to differentially expressed genes. A cuproptosis score (CS) system was established using principal component analysis. The CIBERSORT, ssGSEA and ESTIMATE algorithms were used to assess the tumor immune microenvironment. Moreover, the immunotherapeutic and chemotherapeutic responses were assessed. Results Patients were divided into three cuproptosis subtypes and subsequently regrouped into three gene clusters, reflecting different immune infiltration. Assessed by the CS system, those with higher CSs exhibited worse prognosis and higher TMB frequency. Nevertheless, the immune‐related analysis revealed patients in the low‐CS group appeared immunosuppressive and easily suffered from immune escape. High CSs possibly show high expression of immune checkpoint genes and enhance chemotherapy sensitivity to cisplatin, docetaxel, and gemcitabine. Conclusion We established a novel scoring system to predict the prognosis and immune landscape of HNSCC patients. This signature exhibits satisfactory predictive effects and the potential to guide comprehensive treatment for patients.

“… 10 According to compelling evidence, the programmed cell death process is associated with the immunotherapy response and plays a core role in tumor progression. 2 , 11 …”

Section: Introductionmentioning

confidence: 99%

“…10 According to compelling evidence, the programmed cell death process is associated with the immunotherapy response and plays a core role in tumor progression. 2,11 Copper plays an important role in organisms. The concentrations influence the biological process and induce cell death.…”

Section: Introductionmentioning

confidence: 99%

Identification of cuproptosis‐related subtypes and characterization of the tumor microenvironment landscape in head and neck squamous cell carcinoma

Huang

Yuan

et al. 2022

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“… 4 , 5 , 23 Multiple studies have investigated the correlations between programmed cell death (e.g., pyroptosis)‐related genes and lncRNAs and HNSCC prognosis, assisting in determining clinical outcomes. 24 Necroptosis is reportedly involved in tumor progression and suppression and can be considered a novel therapeutic target for HNSCC patients. 15 , 25 Accordingly, there is a lack of prognostic necroptosis‐related signatures for tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Referring to previous studies, there is a lack of reliable prognostic biomarkers to predict the prognosis of patients with HNSCC, which is increasing worldwide with poor 5‐year survival rates 4,5,23 . Multiple studies have investigated the correlations between programmed cell death (e.g., pyroptosis)‐related genes and lncRNAs and HNSCC prognosis, assisting in determining clinical outcomes 24 15,25 .…”

Section: Discussionmentioning

confidence: 99%

“…4,5,23 Multiple studies have investigated the correlations between programmed cell death (e.g., pyroptosis)-related genes and lncRNAs and HNSCC prognosis, assisting in determining clinical outcomes. 24 Necroptosis is reportedly involved in tumor progression and suppression and can be considered a novel therapeutic target for HNSCC patients. The results of our study showed that there were 29 nrlncRNAs that influenced the survival of HNSCC, and 6 of them (MIR4435-2HG, AC099850.3, AC243829.2, LNCOG, CDKN2A-DT, and SAP30L-AS1) were selected to establish the prognostic signature.…”

Section: Discussionmentioning

confidence: 99%

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Construction of a necroptosis‐related lncRNA signature to predict the prognosis and immune microenvironment of head and neck squamous cell carcinoma

Huang

Teh

et al. 2022

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Background Previous studies have determined that necroptosis‐related genes are potential biomarkers in head and neck squamous cell carcinoma (HNSCC). Herein, we established a novel risk model based on necroptosis‐related lncRNAs (nrlncRNAs) to predict the prognosis of HNSCC patients. Methods Transcriptome and related information were obtained from TCGA database, and an nrlncRNA signature was established based on univariate Cox analysis and least absolute shrinkage and selection operator Cox regression. Kaplan–Meier analysis and time‐dependent receiver operating characteristic (ROC) analysis were used to evaluate the model, and a nomogram for survival prediction was established. Gene set enrichment analysis, immune analysis, drug sensitivity analysis, correlation with N6‐methylandenosin (m6A), and tumor stemness analysis were performed. Furthermore, the entire set was divided into two clusters for further discussion. Results A novel signature was established with six nrlncRNAs. The areas under the ROC curves (AUCs) for 1‐, 3‐, and 5‐year overall survival (OS) were 0.699, 0.686, and 0.645, respectively. Patients in low‐risk group and cluster 2 had a better prognosis, more immune cell infiltration, higher immune function activity, and higher immune scores; however, patients in high‐risk group and cluster 1 were more sensitive to chemotherapy. Moreover, the risk score had negative correlation with m6A‐related gene expression and tumor stemness. Conclusion According to this study, we constructed a novel signature with nrlncRNA pairs to predict the survival of HNSCC patients and guide immunotherapy and chemotherapy. This may possibly promote the development of individualized and precise treatment for HNSCC patients.

Pyroptosis patterns and immune infiltrates characterization in head and neck squamous cell carcinoma

Deng

Wei

Qiu

et al. 2022

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Background: Pyroptosis plays an essential role in tumor immune responses and inflammation related to chemotherapy. Herein, we studied the characteristic patterns of pyroptosis in head and neck squamous cell carcinoma (HNSCC) to determine their prognostic and therapeutic effects. Methods: Consensus clustering analysis was performed to classify patients into pyroptosis or gene clusters. A novel pyroptosis score was constructed by principal component analysis. Kaplan-Meier survival curves were used to show the prognostic value. We also assessed the functional enrichment, tumor mutation burden, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between high and low pyroptosis score group. Results: Two distinct pyroptosis clusters were defined based on the mRNA expression profiles of PRGs, which were related to immune activation in HNSCC. Notably, a pyroptosis score was constructed according to different expression gene signatures, and then, each HNSCC patient was classified into a low or high pyroptosis score group. Patients with low pyroptosis scores had better immunotherapeutic responses and higher sensitivities to chemotherapeutic agents (paclitaxel, docetaxel, and gemcitabine). Kaplan-Meier survival curves showed that the pyroptosis patterns were independent prognostic indicators regardless of the level of tumor mutation burden. Conclusions: Pyroptosis plays an essential role in immune infiltration in HNSCC. Quantifying the pyroptosis score of individual patients might suggest prognostic, immunotherapeutic, and chemotherapeutic strategies for HNSCC.