scholarly journals Development of a Prognostic Pyroptosis-Related Gene Signature for Head and Neck Squamous Cell Carcinoma Patient

Author(s):  
Weiwen Zhu ◽  
Jiayi Zhang ◽  
Mengyao Wang ◽  
Rundong Zhai ◽  
Yanbin Xu ◽  
...  

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). Potential predictors of patient outcomes associated with this 6-gene model were identified through topological degree analyses of a protein-protein interaction network. Lastly, the prognostic value of NLRP3 as a predictor of HNSCC patient prognosis was established through immunohistochemical (IHC) analyses of samples from 176 HNSCC patients.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. IHC analyses further supported the value of NLRP3 as a predictor of HNSCC patient outcomes. 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.

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Francisco Lorenzo-Martín ◽  
Natalia Fernández-Parejo ◽  
Mauricio Menacho-Márquez ◽  
Sonia Rodríguez-Fdez ◽  
Javier Robles-Valero ◽  
...  

Abstract Regenerative proliferation capacity and poor differentiation are histological features usually linked to poor prognosis in head and neck squamous cell carcinoma (hnSCC). However, the pathways that regulate them remain ill-characterized. Here, we show that those traits can be triggered by the RHO GTPase activator VAV2 in keratinocytes present in the skin and oral mucosa. VAV2 is also required to maintain those traits in hnSCC patient-derived cells. This function, which is both catalysis- and RHO GTPase-dependent, is mediated by c-Myc- and YAP/TAZ-dependent transcriptomal programs associated with regenerative proliferation and cell undifferentiation, respectively. High levels of VAV2 transcripts and VAV2-regulated gene signatures are both associated with poor hnSCC patient prognosis. These results unveil a druggable pathway linked to the malignancy of specific SCC subtypes.


2021 ◽  
Author(s):  
Haimei Qin ◽  
Junli Wang ◽  
Biyun Liao ◽  
Zhonglin Liu ◽  
Rong Wang

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is most diagnosed at an advanced stage with poor prognosis. Single gene biomarkers cannot have enough predictive ability in HNSCC. Glycolysis participating in cancers was verified. Thus, this study aimed to identify glycolysis-related gene signature predict the outcome of HNSCC. Methods: The mRNA expression data of HNSCC downloaded The Cancer Genome Atlas (TCGA) project was analyzed by Gene Set Enrichment Analysis (GSEA). We use the Cox proportional regression model to construct a prognostic model. Kaplan–Meier and receiver operating characteristic (ROC) curves were employed to estimate the signature. We also analyzed the relationship of the signature and cancer subtypes. Results: We identified nine glycolysis-related genes including G6PD, EGFR, ALDH2, GPR87, STC2, PDK3, ELF3, STC1 and GNPDA1 as prognosis-related genes signature in HNSCC. HNSCC patients were divided into high and low risk group according to the signature. High risk group showed more poor prognosis and the risk score can precisely predict the prognosis of HNSCC. Additionally, the signature also can be used in cancer subtypes. Conclusion: This study established the 9-mRNA glycolysis signature which may serve as a prospective biomarker for prognosis and novel treatment target in HNSCC.


2020 ◽  
Vol 2020 ◽  
pp. 1-23
Author(s):  
Cai Yang ◽  
Hongxiang Mei ◽  
Liang Peng ◽  
Fulin Jiang ◽  
Bingjie Xie ◽  
...  

Considerable evidence indicates that autophagy plays a vital role in the biological processes of various cancers. The aim of this study is to evaluate the prognostic value of autophagy-related genes in patients with head and neck squamous cell carcinoma (HNSCC). Transcriptome expression profiles and clinical data acquired from The Cancer Genome Atlas (TCGA) database were analyzed by Cox proportional hazards model and Kaplan–Meier survival analysis to screen autophagy-related prognostic genes that were significantly correlated with HNSCC patients’ overall survival. Functional enrichment analyses were performed to explore biological functions of differentially expressed autophagy-related genes (ARGs) identified in HNSCC patients. Six ARGs (EGFR, HSPB8, PRKN, CDKN2A, FADD, and ITGA3) identified with significantly prognostic values for HNSCC were used to construct a risk signature that could stratify patients into the high-risk and low-risk groups. This signature demonstrated great value in predicting prognosis for HNSCC patients and was indicated as an independent prognostic factor in terms of clinicopathological characteristics (sex, age, clinical stage, histological grade, anatomic subdivision, alcohol history, smoking status, HPV status, and mutational status of the samples). The prognostic signature was also validated by data from the Gene Expression Omnibus (GEO) database and International Cancer Genome Consortium (ICGC). In conclusion, this study provides a novel autophagy-related gene signature for predicting prognosis of HNSCC patients and gives molecular insights of autophagy in HNSCC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guichuan Huang ◽  
Jing Zhang ◽  
Ling Gong ◽  
Yi Huang ◽  
Daishun Liu

Abstract Background Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. Methods The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. Results Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. Conclusion A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.


2020 ◽  
Author(s):  
Mabel Catalán ◽  
Catalina Rodríguez ◽  
Ivonne Olmedo ◽  
Javiera Carrasco-Rojas ◽  
Diego Rojas ◽  
...  

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