Identification of a cuproptosis-related lncRNA signature to predict the prognosis and immune landscape of head and neck squamous cell carcinoma

BackgroundCuproptosis is considered a novel copper-induced cell death model regulated by targeting lipoylated TCA cycle proteins. In this study, we established a novel signature based on cuproptosis-related lncRNAs (crlncRNAs) to predict the prognosis and immune landscape of head and neck squamous cell carcinoma.MethodsRNA-seq matrix, somatic mutation files, and clinical data were obtained from The Cancer Genome Atlas database. After dividing patients into two sets, a crlncRNA signature was established based on survival related crlncRNAs, which were selected by the univariate Cox analysis and least absolute shrinkage and selection operator Cox regression. To evaluate the model, Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) were utilized, and a nomogram was established for survival prediction. Immune landscape analysis, drug sensitivity, cluster analysis, tumor mutation burden (TMB) and ceRNA network analysis were conducted subsequently.ResultsA crlncRNA related prognosis signature was finally constructed with 12 crlncRNAs. The areas under the ROC curves (AUCs) were 0.719, 0.705 and 0.693 respectively for 1, 3, and 5-year’s overall survival (OS). Patients in the low-risk group behaved a better prognosis, lower TMB, higher immune function activity and scores. In addition, patients from cluster 2 were more sensitive to chemotherapy and immunotherapy.ConclusionIn this study, we constructed a novel crlncRNA risk model to predict the survival of HNSCC patients. This reliable and acceptable prognostic signature may guide and promote the progress of novel treatment strategies for HNSCC patients

The Association and Clinical Significance of CDKN2A Promoter Methylation in Head and Neck Squamous Cell Carcinoma: a Meta-Analysis

Background/Aims: The association between cyclin-dependent kinase inhibitor 2A (CDKN2A) hypermethylation and head and neck squamous cell carcinoma (HNSCC) risk has been investigated by a number of studies. However, these studies have not demonstrated consistent results. Moreover, the role of CDKN2A methylation in HNSCC carcinogenesis and its clinical significance remain unclear. Methods: We performed a systematic meta-analysis based on 72 articles (including 3399 HNSCCs, 668 premalignant lesions, and 2393 normal controls) from the PubMed, Google Scholar, Web of Science, Embase, China National Knowledge Infrastructure and Wanfang databases. Results: Our study showed a significant increase in the frequency of CDKN2A methylation during HNSCC carcinogenesis (HNSCC vs. normal controls, odds ratio (OR) = 6.72, P < 0.01; HNSCC vs. precancerous lesions, OR = 1.89, P < 0.05; precancerous lesions vs. normal controls, OR = 14.70, P < 0.01). Moreover, CDKN2A methylation was significantly associated with gender (OR = 1.34; P < 0.05) and lymph node metastasis (OR = 2.32; P < 0.01). The area under summary receiver operating characteristic curve (AUC) for diagnosis of HNSCC based on all samples and saliva sample subgroup were 0.77 and 0.96, respectively. Additionally, CDKN2A hypermethylation was significantly associated with shorter overall survival (OS) (hazard ratio (HR) = 1.01, P < 0.05) and recurrence-free survival (RFS) (HR = 1.77, P < 0.05). Conclusion: Our findings indicate CDKN2A methylation is involved in the carcinogenesis, progression, and metastasis of HNSCC. Furthermore, methylated CDKN2A could be a potential diagnostic and prognostic biomarker for HNSCC

Predicting the prognosis, immune response, and immunotherapy in head and neck squamous cell carcinoma using a novel risk model based on anoikis-related lncRNAs

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is an extremely heterogeneous and metastatic disease. Anoikis, which is a specific type of programmed apoptosis, is involved in tumor metastasis, tissue homeostasis, and development. Herein, we constructed an anoikis-related long non-coding RNA (lncRNA) signature to predict the prognosis, immune responses, and therapeutic effects in HNSCC patients. Methods A total of 501 HNSCC samples were acquired from the TCGA database and randomly classified into the training and validation groups (1:1 ratio). Thereafter, the results derived from the training set were analyzed with the LASSO regression analysis, and a novel anoikis-related lncRNA risk model was constructed. Time-dependent ROC curves and Kaplan–Meier analysis were carried out to assess the diagnostic value and survival outcomes. A nomogram was utilized to predict the prognostic accuracy. Furthermore, we studied the tumor microenvironment, tumor mutation burden, enrichment pathways, and the response to chemotherapy and immunotherapy. Results Seven anoikis-related lncRNAs (AC015878.1, CYTOR, EMSLR, LINC01503, LINC02084, RAB11B-AS1, Z97200.1) were screened to design a novel risk model, which was recognized as the independent prognostic factor for HNSCC patients. The findings implied that low-risk patients showed significantly longer OS, PFS, and DSS compared to those high-risk patients. The two groups that were classified using the risk model showed significant differences in their immune landscape. The risk model also predicted that low-risk HNSCC patients could attain a better response to immunotherapy, while high-risk patients would be more sensitive to gemcitabine, docetaxel, and cisplatin. Conclusions We constructed a novel risk model that could be employed for effectively predicting patient prognosis with a good independent prognostic value for HNSCC patients. Furthermore, this model could be used for designing new immunotherapeutic and chemotherapeutic strategies, and it helps clinicians establish personalized and detailed strategies for HNSCC patients

Identification of a disulfidptosis-related lncRNA signature for the prognostic and immune landscape prediction in head and neck squamous cell carcinoma

Abstract Purpose Disulfidptosis, a newly identified form of cell death, is triggered by disulfide stress. Herein, a unique signature was developed based on disulfidptosis-related lncRNAs (DRlncRNAs) for the prognostic and immune landscape prediction of head and neck squamous cell carcinoma (HNSCC). Methods Transcriptome, somatic mutation, and clinical data were acquired at The Cancer Genome Atlas database. Individuals were partitioned into training and test cohorts at a 1:1 ratio to facilitate the development of a DRlncRNA signature using the least absolute shrinkage and selection operation method. Based on the median risk score, all HNSCC individuals were stratified into the high-risk group (HRG) and low-risk group (LRG). Kaplan–Meier survival and time-dependent receiver operating characteristic (ROC) analyses were used to estimate the prognostic value, and a nomogram was generated for survival prediction. To provide a more comprehensive assessment, the tumor microenvironment, functional enrichment, immune cell infiltration, and immunotherapeutic sensitivity were explored between LRG and HRG. Results A DRlncRNA signature was established with 10 DRlncRNAs. The corresponding values of areas under the ROC curves for 1–, 3–, and 5–year overall survival were 0.710, 0.692, and 0.640. A more favorable prognosis was noted in the patients with lower risk, along with higher immune scores, increased immune-related functions, and immune cell infiltration, as well as improved response to the immunotherapeutic intervention in comparison with individuals at higher risk. Conclusion These findings demonstrate that the developed DRlncRNA signature holds promise as a reliable prognostic marker and predictor of immunotherapy response in HNSCC patients

Synthesis and Properties of Flexible Polyurethane Using Ferric Catalyst for Hypopharyngeal Tissue Engineering

Biodegradable polyurethane is an ideal candidate material to fabricate tissue engineered hypopharynx from its good mechanical properties and biodegradability. We thus synthesized a hydrophilic polyurethane via reactions among polyethylene glycol (PEG), e-caprolactone (e-CL) and hexamethylene diisocyanate (HDI), and thrihydroxymethyl propane (TMP). The product possessed a fast degradability due to its good wettability and good mechanical parameters with the elongations at break (137 ± 10%) and tensile strength (4.73 ± 0.46 MPa), which will make it a good matrix material for soft tissue like hypopharynx. Its biological properties were evaluated via in vitro and in vivo tests. The results showed that this hydrophilic polyurethane material can support hypopharyngeal fibroblast growth and owned good degradability and low inflammatory reaction in subcutaneous implantation. It will be proposed as the scaffold for hypopharyngeal tissue engineering research in our future study.Published versio

DNA methylation biomarkers for head and neck squamous cell carcinoma

DNA methylation plays an important role in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). The current study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) by a comprehensive bioinformatics analysis. In addition, we screened for DEGs affected by DNA methylation modification and further investigated their prognostic values for HNSCC. We included microarray data of DNA methylation (GSE25093 and GSE33202) and gene expression (GSE23036 and GSE58911) from Gene Expression Omnibus. Aberrantly methylated-DEGs were analyzed with R software. The Cancer Genome Atlas (TCGA) RNA sequencing and DNA methylation (Illumina HumanMethylation450) databases were utilized for validation. In total, 27 aberrantly methylated genes accompanied by altered expression were identified. After confirmation by The Cancer Genome Atlas (TCGA) database, 2 hypermethylated-low-expression genes (FAM135B and ZNF610) and 2 hypomethylated-high-expression genes (HOXA9 and DCC) were identified. A receiver operating characteristic (ROC) curve confirmed the diagnostic value of these four methylated genes for HNSCC. Multivariate Cox proportional hazards analysis showed that FAM135B methylation was a favorable independent prognostic biomarker for overall survival of HNSCC patients

SHISA3 Promoter Methylation Is a Potential Diagnostic and Prognostic Biomarker for Laryngeal Squamous Cell Carcinoma

The purpose of this study was to evaluate the contribution of SHISA3 promoter methylation to laryngeal squamous cell carcinoma (LSCC). SHISA3 promoter methylation status and expression were determined using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) in 93 paired LSCC and adjacent normal tissues, respectively. Furthermore, the regulatory function of the SHISA3 promoter fragment was analyzed using a luciferase reporter assay. The results reveal that there is a significant increase in SHISA3 methylation in LSCC tissues compared with corresponding nontumor tissues P=4.58E-12. The qRT-PCR results show a significant association between SHISA3 methylation and expression in LSCC P=1.67E-03. In addition, the area under the receiver operating characteristic curve was 0.91. Consequently, a log-rank test and multivariate Cox analysis suggest that SHISA3 promoter hypermethylation is a predictor of poor overall survival for LSCC (log-rank P = 0.024; HR = 2.71; 95% CI = 1.024–7.177; P = 0.047). The results indicate that SHISA3 promoter hypermethylation might increase the risk of LSCC through regulation of gene expression and is a potential diagnostic and prognostic biomarker for LSCC