A Ferroptosis-Related Gene Signature for Predicting the Prognosis and Drug Sensitivity of Head and Neck Squamous Cell Carcinoma

Lü, Wei; Wu, Yihua; Huang, Shengyun; Zhang, Dongsheng

doi:10.3389/fgene.2021.755486

Cited by 11 publications

(11 citation statements)

References 59 publications

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“…Ferroptosis is morphologically, biochemically, and genetically distinct from other cell deaths, suggesting its therapeutic potential for HNSCC. Recently, sequence-based studies have shown that ferroptosis-related gene signature plays an important role in the development and treatment of HNSCC [ 18 – 20 ]. CAV1, which could inhibit ferroptosis, leads to cancer progression in HSNCC [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Epithelial Membrane Protein 1 Promotes Sensitivity to RSL3-Induced Ferroptosis and Intensifies Gefitinib Resistance in Head and Neck Cancer

Wang

Zhang

Yao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Epithelial membrane protein (EMP1), a member of the peripheral myelin protein (PMP22) family, is involved in the development of various human malignancies. However, the expression level of EMP1 and its functional role in head and neck squamous cell carcinoma (HNSCC) remain unclear to date. Ferroptosis, a newly characterized form of regulated cell death, plays an essential role in tumorigenesis. In this study, we aimed to investigate the expression levels of EMP1 in HNSCC and normal tissues, as well as to identify the function of EMP1 in regulating ferroptosis during the progression of HNSCC. To further explore the biological function of EMP1 in vitro, transient transfection was used to overexpress EMP1 in the HNSCC cell lines Hep2 and Detroit562. Functionally, our results indicated that EMP1 overexpression could not affect the initiation of ferroptosis directly but reinforced RSL3-induced ferroptosis on HNSCC cells. Furthermore, mechanical study indicated that EMP1 mediated the ferroptosis via cell density-regulated Hippo-TAZ pathway and regulated the expression of Rac1 and NOX1. In addition, our study demonstrated that EMP1 overexpression could promote gefitinib resistance by targeting the MAPK pathway. In summary, our findings indicate that EMP1 may act as an oncogene and serve as a therapeutic target against malignant progression of HNSCC.

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Section: Introductionmentioning

confidence: 99%

Epithelial Membrane Protein 1 Promotes Sensitivity to RSL3-Induced Ferroptosis and Intensifies Gefitinib Resistance in Head and Neck Cancer

Wang

Zhang

Yao

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…BNIP3 is regarded as a proapoptotic protein, whose dysregulated expression is related to mitophagy, autophagy, and pyroptosis [67][68][69]. Tumor cells are sensitive to cisplatin and gemcitabine when BNIP3 upregulates [70]. Interestingly, the expression level of BNIP3 will elevate in early-stage adenocarcinoma but decrease in metastasis progression.…”

Section: Discussionmentioning

confidence: 99%

Pyroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Non-Small-Cell Lung Cancer

Luo

Yao

Xiang

2022

Oxidative Medicine and Cellular Longevity

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Non-small-cell lung cancer (NSCLC) has a high incidence and mortality worldwide. Moreover, it needs more accurate means for predicting prognosis and treatments. Pyroptosis is a novel form of cell death about inflammation which was highly related to the occurrence and development of tumors. Despite having some studies about pyroptosis-related genes (PRGs) and cancer, the correlation has not been explored enough between PRGs and immune in NSCLC. In this study, we constructed a PRG model by WGCNA to access the prognosis value PRGs have. The testing cohort ( n = 464 ) with four datasets from the GEO database conducted a survival analysis to confirm the stability of the prognostic model. The risk score and age are examined as independent prognostic factors. Based on the PRGs, we found multiple pathways enriched in immune in NSCLC. Separating samples into three subtypes by consensus cluster analysis, Cluster 3 was identified as immune-inflamed phenotype with an optimistic prognostic outcome. A three-gene PRG signature (BNIP3, CASP9, and CAPN1) was identified, and BNIP3 was identified as the core gene. Knockdown of BNIP3 significantly inhibited the growth of H358 cells and induced pyroptosis. In conclusion, the model construction based on PRGs provides novel insights into the prediction of NSCLC prognosis, and BNIP3 can serve as a diagnostic biomarker for NSCLC.

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“…The ROC curve and decision curve analysis (DCA) were also used to assess the precision of the model compared to the traditional clinical features. The comparison between the established models was utilized to assess the forecasting ability of the novel model [ 16 , 24 – 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…e comparison between the established models was utilized to assess the forecasting ability of the novel model [16,[24][25][26][27][28].…”

Section: Establishment Of the Risk Modelmentioning

confidence: 99%

Identification of Ferroptosis-Related lncRNA Pairs for Predicting the Prognosis of Head and Neck Squamous Cell Carcinoma

Wu¹,

Liu

Chen

et al. 2022

Journal of Oncology

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Background. Ferrogenesis was strongly associated with tumorigenesis and development, and activating the ferrogenic process was a novel regimen in treating cancer, especially conventional treatment-resistant cancers. The purpose of the article was to construct a ferroptosis-related long noncoding RNAs (FRlncRNAs) signature, regardless of expression levels to effectively predict prognosis and immunotherapeutic response for head and neck squamous cell carcinoma (HNSCC). Methods. The RNA-seq data for HNSCC and corresponding clinical information were obtained in the TCGA database, and ferroptosis-related genes (FRGs) were extracted in the ferroptosis database. On this basis, differentially expressed FRlncRNAs (DEFRlncRNAs) pairs were identified through coexpression analysis, differential expression analysis, and a fresh pairing algorithm. Then, a risk assessment model was established with univariate Cox, LASSO, and multivariate Cox regression analysis. Finally, we evaluated the model from various aspects, including survival status, clinicopathological characteristics, infiltration status of immune cells, immune functions, chemotherapeutic sensitivity, immune checkpoint inhibitors (ICIs)-related molecules, and N6-methyladenosine (m6A) mRNA status. Result. We established a signature of 11-DEFRlncRNA pairs related to the prognosis of HNSCC that had AUC values above 0.75 in the one-, three-, and five-year ROC curves, underscoring the high susceptibility and specifiability of predicting HNSCC prognosis. Survival rates were remarkably higher for the low-risk patients than for the high-risk patients, and the signature was significantly correlated with survival, clinical, T, and N stages. Finally, immune cell infiltration status, immune functions, chemotherapeutic sensitivity, and expression levels of ICIs-related and m6A-related molecules were statistically different among different groups. Conclusion. Our study established a novel lncRNA signature, which is independent of specific expression levels, could predict patient prognosis, and might have promising clinical applications in HNCSS.

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A Ferroptosis-Related Gene Signature for Predicting the Prognosis and Drug Sensitivity of Head and Neck Squamous Cell Carcinoma

Cited by 11 publications

References 59 publications

Epithelial Membrane Protein 1 Promotes Sensitivity to RSL3-Induced Ferroptosis and Intensifies Gefitinib Resistance in Head and Neck Cancer

Epithelial Membrane Protein 1 Promotes Sensitivity to RSL3-Induced Ferroptosis and Intensifies Gefitinib Resistance in Head and Neck Cancer

Pyroptosis-Related Gene Model Predicts Prognosis and Immune Microenvironment for Non-Small-Cell Lung Cancer

Identification of Ferroptosis-Related lncRNA Pairs for Predicting the Prognosis of Head and Neck Squamous Cell Carcinoma

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