Identification of pyroptosis-related gene prognostic signature in head and neck squamous cell carcinoma.

Head 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. The 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. We 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. We 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.

Li Z ，Shen L ，Li Y ，Shen L ，Li N ... -  《Cancer Medicine》

Identification and validation of a prognostic signature of autophagy, apoptosis and pyroptosis-related genes for head and neck squamous cell carcinoma: to imply therapeutic choices of HPV negative patients.

An effective tool is needed to predict the prognosis of head and neck squamous cell carcinoma (HNSCC). Human papillomavirus (HPV) positive HNSCC patients generally have a favorable survival and a promising responsiveness to radiotherapy, chemoradiotherapy and checkpoint blockades. However, HPV negative patients, the majority of HNSCC patients, have been largely overlooked. Cell death has been involved in the therapeutic resistance of cancers. To this end, we aimed to identify the association of autophagy, apoptosis and pyroptosis-related genes with the prognosis of HNSCC, and construct a prognostic signature to predict the prognosis for HNSCC, especially for HPV negative HNSCC. Autophagy and apoptosis-related genes were obtained from Gene Set Enrichment Analysis (GSEA) website, and pyroptosis-related genes were obtained from GSEA and Gene Ontology (GO) database. We established the cell death index (CDI) based on RNA sequencing (RNA-seq) data and clinicopathological information from The Cancer Genome Atlas (TCGA) dataset. The prognostic value of CDI was verified by Kaplan-Meier, receiver operating characteristic (ROC) and univariate and multivariate Cox regression analyses in TCGA dataset, and validated with the datasets from Gene Expression Omnibus (GEO) and Qilu Hospital of Shandong University. We further assessed the immune microenvironment of patients with high and low CDI scores. Moreover, the expression of the signature genes in HNSCC cell lines were explored. We found that CDI was an independent prognostic indicator for overall survival (hazard ratio 3.80, 95% confidential interval: 2.70-5.40, P < 0.001). Furthermore, HNSCC patients with high CDI scores obtained increased overall survival post radiation indicating benefits from radiotherapy of this subgroup. On the other hand, HPV negative HNSCC patients with low CDI exhibited increased checkpoint gene expressions, an inflamed tumor microenvironment and an enriched immune response-related functions, suggesting the potential benefits from checkpoint immunotherapies of this subgroup. Moreover, we validated the baseline and induced expressions of above 16 genes in two HPV negative HNSCC cell lines, CAL27 and SCC-15. We established a prognostic signature and emphasized its implements in the therapeutic choices of HPV negative HNSCC patients, the majority and the poor outcome population of HNSCC.

Nan Z ，Dou Y ，Chen A ，Wang K ，Sun J ，Meng Z ，Neckenig M ，Ai D ，Liu S ，Dong Z ，Ma C ，Cheng Y ，Qu X ... -  《Frontiers in Immunology》

A pyroptosis-related gene expression signature predicts immune microenvironment and prognosis in head and neck squamous cell carcinoma.

Zhou W ，Feng M ，Qi F ，Qiao J ，Fan L ，Zhang L ，Hu X ，Huang C ... -  《-》

A pyroptosis-related lncRNA signature predicts prognosis and immune microenvironment in head and neck squamous cell carcinoma.

Pyroptosis, a type of regulated cell death controlled by the gasdermin family of proteins to form plasma membrane pores is known. Nonetheless, the function of pyroptosis-related long non-coding RNAs (lncRNAs) in this process still lacks exhaustive elucidation in head and neck squamous cell carcinoma (HNSCC). Other attributes encompassing the function of such lncRNAs in the immune microenvironment and potential prognosis for HNSCC are yet to see the light of the day. This work was designed to probe the possible prognostic worth of pyroptosis-related lncRNAs along with their impact on the immune microenvironment in the case of HNSCC. The Cancer Genome Atlas (TCGA) database was the source of RNA-sequencing data of HNSCC patients. Pearson correlation analysis was employed to scour for lncRNAs linked to pyroptosis based on 40 genes related to the process. Following the construction of a pyroptosis-related lncRNA signature employing univariate, Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses, survival and nomogram analyses ensued to scrutinize the predictive value of the prognostic signature. The segregation of patients into two risk groups was done by the constructed pyroptosis-related-lncRNA signature (encompassing 14 lncRNAs). The prognosis was poorer for individuals of the high-risk group versus (vs.) the low-risk group with the risk score emerging as an independent prognostic factor by regression analyses. The accuracy of this signature was corroborated by Receiver operating characteristic curve (ROC) analysis with the three-years area under time-dependent ROC curve (AUC) reaching 0.767. Further analyses unveiled a conspicuous enrichment of immune-related pathways in the low-risk group. The high-risk group demonstrated an immunologically "cold" profile based on the immune cell infiltration landscape. The lncRNA signature encompassing 14 pyroptosis-related lncRNAs could be a prognostic marker for HNSCC, suggesting pyroptosis might be a promising therapeutic target in HNSCC.

Zhu W ，Ye Z ，Chen L ，Liang H ，Cai Q ... -  《-》

A novel Pyroptosis-related long non-coding RNA signature for predicting the prognosis and immune landscape of head and neck squamous cell carcinoma.

Pyroptosis plays an essential function in carcinogenesis and the antitumor immune response. Herein, we constructed a pyroptosis-related long noncoding RNA (prLncRNA) signature to predict therapeutic effects and outcomes for head and neck squamous cell carcinoma (HNSCC) patients. Patients obtained from the TCGA-HNSC project were divided randomly into the training as well as the validation sets at a ratio of 7:3. A novel prognostic prLncRNA signature was constructed from the results of the training set using the least absolute shrinkage and selection operation. The medium value was used as the basis for categorizing all HNSCC patients into a low- or high-risk cohort. Cox regression and Kaplan-Meier (KM) survival analyses were executed to estimate the prognostic value. We also evaluated the functional enrichment, tumor microenvironment, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between the high- and low-risk cohorts. Nineteen prognostic prlncRNAs were identified to establish the prognostic signature. Multivariate Cox regression and KM survival analyses confirmed that this prlncRNA signature might serve as an independent prognostic indicator of patient survival, which was subsequently confirmed using a validating dataset. Multiple ROC curves indicated the prlncRNA signature presented a more predictive power than clinicopathological factors (age, sex, tumor grade, and tumor stage). GO, KEGG, and GSEA enrichment analysis disclosed several immune-related pathways which appeared to be enhanced in the low-risk cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithms indicated considerable differences in the tumor microenvironment and immune cell infiltration in the low- and high-risk cohorts. Furthermore, the low-risk cohort was predicted to achieve a better response to immunotherapeutic drugs, while in contrast, the high-risk cohort would be more sensitive to chemotherapy drugs. Our findings robustly demonstrate that our constructed prlncRNA signature could serve as an efficient indicator of prognosis, immunotherapy response, and chemosensitivity for HNSCC patients.

Zhou C ，Shen Y ，Jin Y ，Shen Z ，Ye D ，Shen Y ，Deng H ... -  《Cancer Medicine》