Prognosis Of Head And Neck Squamous Cell Carcinoma Research Articles

Exploring the evolving roles and clinical significance of circRNAs in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) represents the predominant malignancies in the head and neck region, and has limited therapeutic alternatives. Circular RNAs (circRNAs), a substantial category of non-coding RNA molecules, exert influential roles in human disease development and progression, employing various mechanisms such as microRNA sponging, interaction with RNA-binding proteins, and translational capabilities. Accumulating evidence highlights the differential expression of numerous circRNAs in HNSCC, and numerous dysregulated circRNAs underscore their crucial involvement in malignant advancement and resistance to treatment. This review aims to comprehensively outline the characteristics, biogenesis, and mechanisms of circRNAs, elucidating their functional significance in HNSCC. In addition, we delve into the clinical implications of circRNAs, considering their potential as biomarkers or targets for diagnosis, prognosis, and therapeutic applications in HNSCC. The discussion extends to exploring future challenges in the clinical translation of circRNAs, emphasizing the need for further research.

Biomarker Potential of LINC00313 in Head and Neck Squamous Cell Carcinoma: Correlation with Epithelial-Mesenchymal Transition and Immune Cell Infiltration.

Although LINC00313 is dysregulated in several tumors, its role in head and neck squamous cell carcinoma (HNSC) is not fully understood. The aim of this study was to analyze the role of LINC00313 in HNSC. The clinical information and LINC00313 expression data of HNSC were mined from the TCGA/GEO/cbioportal database. The correlation between LINC00313 expression and immune cell infiltration in HNSC tumors was analyzed by bioinformatics and gene enrichment analysis was performed. LINC00313 was silenced in HNSC cell lines, and changes at the genetic and molecular levels were verified through qRT-PCR and Western blotting. The researchers also validated its functional phenotype through a series of cell function experiments. The results showed that overexpression and copy number variation of LINC00313 in HNSC were associated with poorer prognosis. In addition, LINC00313 expression was significantly negatively correlated with immune cell infiltration. Silencing of LINC00313 in HNSC cells significantly reduced the rate of cell migration. LINC00313 may affect the progression of HNSC by regulating epithelial-mesenchymal transition. In conclusion, LINC00313 is a potential biomarker of HNSC prognosis and a potential target for immunotherapy.

Panoramic analysis of cell death patterns reveals prognostic and immune profiles of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has been characterized by a low therapeutic response and poor prognosis. Currently, there are no reliable predictive models for HNSCC progression and therapeutic efficacy. This study explores the role of diverse patterns of cell death in tumor development, positing them as predictive factors of HNSCC prognosis. We utilized bulk transcriptome and single-cell transcriptome, align with clinical information from TCGA and GEO database, to analyze genes associated with 15 types of cell death and construct a cell death index (CDI) signature. The associations of CDI with tumor-infiltrating immune cells and immunotherapy-related biomarkers were also evaluated using various algorithms. The CDI signature emerged as a robust prognosis biomarker that could identify patients who can benefit potentially from immunotherapy, thus improving diagnostic accuracy and optimizing clinical decisions in HNSCC management. Notably, we discovered that CAAP1 deficiency not only induced apoptosis but also enhanced anti-tumor immunity, suggesting its potential as a target for clinical drug development.

CXC ligand 13 orchestrates an immunoactive microenvironment and enhances immunotherapy response in head and neck squamous cell carcinoma.

Objectives: This study aims to systematically explore the role of chemokine CXC ligand 13 (CXCL13) in head and neck squamous cell carcinoma (HNSCC). Methods: The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases provided the RNA-seq data for cancer and normal tissues, respectively. Gene set enrichment analysis was applied to search the cancer hallmarks associated with CXCL13 expression. TIMER2.0 was the main platform used to investigate the immune cell infiltration related to CXCL13. Immunohistochemistry was applied to explore the relationship between CXCL13 and patients' prognosis and the relationship between CXCL13 and tertiary lymphoid structures (TLSs). Results: The expression of CXCL13 was upregulated in most tumors, including HNSCC. The higher expression of CXCL13 was closely related to the positive prognosis of HNSCC. CXCL13 was mainly expressed in B cells and CD8 + T cells, revealing the relationship between its expression and immune activation in the tumor microenvironment. Furthermore, immunohistochemistry and multiple fluorescence staining analysis of HNSCC samples showed a powerful correlation between CXCL13 expression, TLSs formation, and positive prognosis. Finally, CXCL13 significantly increased the response to cancer immunotherapy. Conclusions: CXCL13 may function as a potential biomarker for predicting prognosis and immunotherapy response and associate with TLSs in HNSCC.

Clinicopathologic characteristics of HPV-associated head and neck squamous cell carcinoma in Southern China: long-term retrospective study of 400 cases.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an evolving and growing disease, especially in developing countries. However, the clinical characteristics of HPV-associated HNSCC in regard to HPV infection rates, patient features, and prognosis are under-reported in the Asian population. In this study, we retrospectively enrolled a 400-case cohort of HNSCC with p16 immunochemistry and analyzed with long-term follow-up. We investigate the current HPV prevalence of HNSCC, unique HPV-associated patient clinical characteristics, and patient prognosis in the southern China population. HPV infection exhibited a 15% prevalence in all HNSCC cases, notably higher in oropharyngeal cases (30.7%), followed by oral cavity (11.8%), laryngeal (10.1%), and hypopharyngeal (2.5%). HPV status, gender, old age, and location of tumor were significantly associated with the patient's survival. Tonsil invasion was found more frequent in HPV-positive oropharyngeal HNSCC than in HPV-negative cases. HPV-associated HNSCC patients tend to possess stronger tobacco and alcohol habits, which were correlated to poor survival. HPV status's correlation with gender, age, and anatomical location is associated intricately with patient survival. The secondary primary tumor rate was found higher within the HPV-negative group, compared to the HPV-positive group (9.12% versus 1.67%). Our study provided a current picture of HPV-associated HNSCC in the southern China population and elaborated the understanding of key factors that correlate to HNSCC prognosis. Our findings indicated a strong susceptibility of HPV-associated oropharyngeal HNSCC in the tonsil and the difference in secondary primary tumor rates associated with HPV status.

A novel oxidative stress-related gene signature as an indicator of prognosis and immunotherapy responses in HNSCC.

To identify molecular subtypes of oxidative stress-related genes in head and neck squamous cell carcinoma (HNSCC) and to construct a scoring model of oxidative stress-related genes. R language based scRNA-seq and bulk RNA-seq analyses were used to identify molecular isoforms of oxidative stress-related genes in HNSCC. An oxidative stress-related gene scoring (OSRS) model was constructed, which were verified through online data and immunohistochemical staining of clinical samples. Using TCGA-HNSCC datasets, nine predictive genes for overall patient survival, rarely reported in previous similar studies, were screened. AREG and CES1 were identified as prognostic risk factors. CSTA, FDCSP, JCHAIN, IFFO2, PGLYRP4, SPOCK2 and SPINK6 were identified as prognostic factors. Collectively, all genes formed a prognostic risk signature model for oxidative stress in HNSCC, which were validated in GSE41613, GSE103322 and PRJEB23709 datasets. Immunohistochemical staining of SPINK6 in nasopharyngeal cancer samples validated the gene panel. Subsequent analysis indicated that subgroups of the oxidative stress prognostic signature played important roles during cellular communication, the immune microenvironment, the differential activation of transcription factors, oxidative stress and immunotherapeutic responses. The risk model might predict HNSCC prognosis and immunotherapeutic responses.

Prognostic significance of senescence-related tumor microenvironment genes in head and neck squamous cell carcinoma.

The impact of the senescence related microenvironment on cancer prognosis and therapeutic response remains poorly understood. In this study, we investigated the prognostic significance of senescence related tumor microenvironment genes (PSTGs) and their potential implications for immunotherapy response. Using the Cancer Genome Atlas- head and neck squamous cell carcinoma (HNSC) data, we identified two subtypes based on the expression of PSTGs, acquired from tumor-associated senescence genes, tumor microenvironment (TME)-related genes, and immune-related genes, using consensus clustering. Using the LASSO, we constructed a risk model consisting of senescence related TME core genes (STCGs). The two subtypes exhibited significant differences in prognosis, genetic alterations, methylation patterns, and enriched pathways, and immune infiltration. Our risk model stratified patients into high-risk and low-risk groups and validated in independent cohorts. The high-risk group showed poorer prognosis and immune inactivation, suggesting reduced responsiveness to immunotherapy. Additionally, we observed a significant enrichment of STCGs in stromal cells using single-cell RNA transcriptome data. Our findings highlight the importance of the senescence related TME in HNSC prognosis and response to immunotherapy. This study contributes to a deeper understanding of the complex interplay between senescence and the TME, with potential implications for precision medicine and personalized treatment approaches in HNSC.

Sixteen Cellular Senescence-associated DNA Methylation Signature Predicts Overall Survival in Patients with Head and Neck Squamous Cell Carcinoma.

To construct a cellular senescence-related DNA methylation model to act as an independent prognosis predictor for patients with head and neck squamous cell carcinoma (HNSCC). Methylome, transcriptome and clinical information for 499 HNSCC patients were received from The Cancer Genome Atlas (TCGA) as a training set. An extra independent methylation dataset of 54 patients with oral squamous cell carcinoma (OSCC) was downloaded from the NCBI Gene Expression Omnibus (GEO) database as the validation set. To assess the cellular senescence level of each sample, the senescence score (SS) of each patient was calculated using the transcriptome data via single-sample gene set enrichment analysis (ssGSEA). Least absolute shrinkage and selection operator (LASSO) Cox regression analyses were conducted to confirm Cytosine, phosphoric acid and Guanine (CpG) sites for the development of a cellular senescence-related DNA methylation signature. Based on the SS of each HNSCC patient in the TCGA cohort, the patients were divided into high- and low-SS subgroups. The high-SS group showed a better prognosis than the low-SS group. Moreover, 3,261 differentially methylated CpG sites (DMCs) were confirmed between the two groups. Among them, 16 DMCs were included to develop a 16-DNA methylation signature for evaluation of HNSCC prognosis using LASSO and multivariate Cox regression analysis. A novel cellular senescence-related 16-DNA methylation signature was determined, which can be used as an independent index to evaluate the prognosis of HNSCC patients and select appropriate treatment strategies.

TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma.

Treatment resistance and relapse are common problems in head and neck squamous cell carcinoma (HNSCC). Except for p16, no clinically accepted prognostic biomarkers are available for HNSCC. New biomarkers predictive of recurrence and survival are crucial for optimal treatment planning and patient outcome. High translocator protein (TSPO) levels have been associated with poor survival in cancer, but the role of TSPO has not been extensively evaluated in HNSCC. TSPO expression was determined in a large population-based tissue microarray cohort including 611 patients with HNSCC and evaluated for survival in several clinicopathological subgroups. A TCGA HNSCC cohort was used to further analyze the role of TSPO in HNSCC. TSPO expression was downregulated in more aggressive tumors. Low TSPO expression associated with worse 5-year survival and was an independent prognostic factor for disease-specific survival. Subgroup analyses showed that low TSPO expression associated with worse survival particularly in p16-positive oropharyngeal cancer. In silico analyses supported the prognostic role of TSPO. Cellular respiration had the highest significance in pathway analyses for genes expressed positively with TSPO. Decreased TSPO expression associates with poor prognosis in HNSCC. TSPO is a prognostic biomarker in HNSCC to potentially guide treatment stratification especially in p16-positive oropharyngeal cancer.

Tumor-derived extracellular vesicles in the immune microenvironment of head and neck squamous cell carcinoma: Foe or future?

Head and neck squamous cell carcinoma (HNSCC) is considered a “cold tumor” due to its suppressive immune microenvironment, and is associated with a poor prognosis. Tumor-derived extracellular vesicles (EVs) play an essential role in the tumor microenvironment and mediate intercellular communications. EVs have been proven to be key immune regulators involved in antitumor immune responses and escape from immune surveillance. Tumor-derived EVs favor the formation of an immunosuppressive tumor microenvironment by regulating the differentiation, proliferation and activation of innate and adaptive immune effector cells, as well as myeloid cells, acting as a “foe” in the microenvironment. However, EVs are also valuable for predicting and improving the prognosis of HNSCC, and represent hope for future treatments. In this review, we summarize the impact of HNSCC-derived EVs on the immune microenvironment, describe their roles as biomarkers and for drug delivery in disease monitoring and treatment. We provide insights into important areas for future research and identify potential therapeutic targets for HNSCC treatment.

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

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and aggressive malignancy with a poor prognosis. Pyroptosis triggered by gasdermins family proteins is reported vital for tumor microenvironment and cancer progression. However, pyroptosis-related gene expression and its relationship with immune infiltration and prognosis of HNSCC have not been fully defined. RNA-sequencing data of HNSCC patients were acquired from The Cancer Genome Atlas (TCGA) database. A pyroptosis-related gene expression signature and infiltrated immune cells were analyzed. Univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression and nomogram analyses were used to construct a clinical-molecular risk model for survival prognosis. HNSCC was classified into three different molecular subtypes based on the expression information of pyroptosis-related genes. Immune cell infiltration was demonstrated to be distinct between the three subtypes. The segregation of patients into the high-risk group and low-risk group, were carried out using the signature of differential expression genes (DEGs) signature among the three molecular subtypes. The precision of this signature was corroborated by Receiver operating characteristic curve (ROC) analysis with the 3-year area under time-dependent ROC curve (AUC) reaching 0.711. The risk model was validated in another dataset from the Gene Expression Omnibus (GEO) database. Subsequently we established a clinical-molecular nomogram which combined the risk score with age and stage. The calibration plots for predicting the overall survival rate of 1-, 3-, and 5-years indicated that the nomogram performs well. The expression signature that encompasses pyroptosis-related genes could be used as molecular classification for HNSCC and pyroptosis might be a promising therapeutic target in HNSCC.

Increased Expression of LIPC Is Associated With the Clinicopathological Features and Development of Head and Neck Squamous Cell Carcinoma.

Introduction Lipase C hepatic type (LIPC) is a member of the lipase family and plays a role in tumor development. However, its specific role in head and neck squamous cell carcinoma (HNSCC) is not well understood. Objective This study aims to investigate LIPC gene expression in HNSCC and elucidate its potential role in the context of the disease. Methods LIPC expression was analyzed using the Cancer Genome Atlas-HNSCC (TCGA-HNSCC) dataset. Real-time polymerase chain reaction (qPCR) was used to validate LIPC expression in oral squamous cell carcinoma (OSCC) tissue samples, which is the most common type of HNSCC. The LIPC was assessed to find out if there is a link with HNSCC clinicopathological features, prognosis, and tumor infiltration. Functional pathways associated with the LIPC network were also examined. Results LIPC expression was found to be elevated in both HNSCC and OSCC tissues. The heightened expression of LIPC correlated with various clinicopathological features and influenced the prognosis of HNSCC patients. The LIPC gene demonstrated connections with several oncogenic genes and proteins, participating in lipid catabolic processes and other pathways. These findings suggest that LIPC expression may play a role in the pathogenesis of HNSCC. Conclusion Our study affirms that LIPC expression is linked to the development of HNSCC, suggesting its potential utility as a biomarker or therapeutic target for the disease. However, further functional studies are imperative to validate and expand upon these findings.

Phosphoglycerate-kinase-1 Is a Potential Prognostic Biomarker in HNSCC and Correlates With Immune Cell Infiltration.

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer worldwide, with a high recurrence rate and a low cure rate. Phosphoglycerate kinase 1 (PGK1), an essential enzyme in the aerobic glycolysis pathway, is a prognostic marker for a variety of cancers. However, it remains unclear whether a PGK1-based immune signature can be used as a prognostic biomarker in HNSCC patients. We explored the potential oncogenic mechanisms of PGK1 by multiple bioinformatics analyses combined with multiple databases, including the correlation between PGK1 and prognosis, and the infiltration of immune cells in HNSCC. Functional enrichment analyses were further performed to investigate the potential role of PGK1 in HNSCC. The expression of PGK1 was significantly higher in HNSCC tissues compared to normal tissues. High expression of PGK1 was associated with poor prognosis in HNSCC, and multivariate cox regression analysis showed that PGK1 could be an independent prognostic factor in HNSCC. Pathway analysis revealed that PGK1 may regulate the pathogenesis of HNSCC through the immune signaling pathway. Moreover, PGK1 expression significantly correlated with the infiltration level of 16 types of immune cells. The current study reports that PGK1 expression was increased in HNSCC and that high PGK1 expression was closely associated with poor prognosis and immune cell infiltration, which could serve as a promising independent prognostic biomarker and potential immunotherapeutic target for HNSCC.

A prognostic model based on Scissor+ cancer associated fibroblasts identified from bulk and single cell RNA sequencing data in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is one of the most lethal diseases in the world, which often recur after multimodality treatment approaches, leading to a poor prognosis. Fibroblasts, a heterogeneous component of the tumor microenvironment, can modulate numerous aspects of tumor biology and have been increasingly acknowledged in dictating the clinical outcome of patients with HNSCC. However, the subpopulation of fibroblasts that are related to the prognosis of HNSCC has not yet been fully explored. To do so, we combined a single-cell RNA sequencing (scRNA-seq) dataset and bulk RNA-sequencing dataset with clinical information, identifying the fibroblast population that are related to poor prognosis of HNSCC. We found these specific population of fibroblasts are less differentiated. In addition, to identify the prognostic signatures of HNSCC, bioinformatics analysis included least absolute shrinkage and selection operator (LASSO) analyses and univariate cox and were performed. We selected 12 prognosis-related genes for constructing a risk model using The Cancer Genome Atlas (TCGA). The AUC values and calibration plots of this model indicated good prognostic prediction efficacy. This model also was validated in two Gene Expression Omnibus (GEO) datasets. In conclusion, we constructed an optimal model that was derived from single cell RNA-seq and bulk RNA-seq to predict the survival probability of HNSCC patients. Among this model, AKR1C3 higher expression in cancer associated fibroblasts (CAFs) of HNSCC has been confirmed by preliminary experiments.

MTDH enhances radiosensitivity of head and neck squamous cell carcinoma by promoting ferroptosis based on a prognostic signature.

Ionizing radiation (IR) induces ferroptosis in head and neck squamous cell carcinoma (HNSCC). But, it remains unclear whether ferroptosis affects the prognosis of HNSCC patients after receiving radiotherapy. This study aims to develop a ferroptosis signature to predict the radiosensitivity and prognosis of HNSCC. Ferroptosis-related genes, clinical data and RNA expression profiles were obtained from the FerrDb database, The Cancer Genome Atlas and GEO database. Prognostic genes were identified by random survival forest, univariate Cox regression, Kaplan-Meier and ROC analyses. Principal component analysis, multivariate Cox regression, nomogram and DCA analyses were conducted to estimate its predictive ability. Functional enrichment and immune-related analyses were performed to explore potential biological mechanisms and tumor immune microenvironment. The effect of the hub gene on ferroptosis and radiosensitivity was verified using flow cytometry, quantitative real-time PCR and clonogenic survival assay. We constructed a ferroptosis-related signature, including IL6, NCF2, metadherin (MTDH) and CBS. We classified patients into high-risk (HRisk) and low-risk groups according to the risk scores. The risk score was confirmed to be an independent predictor for overall survival (OS). Combining the clinical stage with the risk score, we established a predictive nomogram for OS. Furthermore, pathways related to tumorigenesis and tumor immune suppression were mainly enriched in HRisk. MTDH was verified to have a potent effect on IR-induced ferroptosis and consequently promoted radiosensitivity. We constructed a ferroptosis-related signature to predict radiosensitivity and OS in HNSCC patients. MTDH was identified as a promising therapeutic target in radioresistant HNSCC patients.

FTH1 indicates poor prognosis and promotes metastasis in head and neck squamous cell carcinoma.

Currently, ferritin heavy chain (FTH1) has been increasingly found to play a crucial role in cancer as a core regulator of ferroptosis, while its role of non-ferroptosis in head and neck squamous cell carcinoma (HNSCC) is still unclear. Herein, we analyzed the expression level of FTH1 in HNSCC using TCGA database, and FTH1 protein in HNSCC tissues and cell lines was determined by immunohistochemistry (IHC) and western blotting, respectively. Then, its prognostic value and relationship with clinical parameters were investigated in HNSCC patients. Additionally, the biological function of FTH1 in HNSCC was explored. The current study showed that FTH1 is significantly overexpressed in HNSCC tissues and related to poor prognosis and lymph node metastasis of HNSCC. FTH1 knockdown could suppress the metastasis and epithelial-mesenchymal transition (EMT) process of HNSCC. Our findings indicate that FTH1 plays a critical role in the progression and metastasis of HNSCC and can serve as a promising prognostic factor and therapeutic target in HNSCC.

A novel necroptosis-related model predicts the prognosis and immunocompetence of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a disease characterized by profound immunosuppression and the prognosis of HNSCC patients remains poor. Necroptosis is a programmed lytic cell-death mechanism that can promote tumor growth, angiogenesis, invasion and metastasis. The differentially expressed NRGs were screened by using the LIMMA package of R software (version 4.1.2) and the prognosis-related NRGs were obtained by COX regression analysis. We separated patients into high- and low-risk groups via the prognostic model consisting of those NRGs. The receiver operating characteristic (ROC) curve and Kaplan-Meier survival curves were used to validate the prognostic model. By bioinformatics analysis, the prognostic risk and immunocompetent models were constructed. We reevaluate the prognostic model based on the GES27020 data sets, clinicopathological variables and chemotherapeutic efficacy. Individuals in the high-risk group had much shorter overall survival (OS) times than their counterparts. Compared with clinicopathological variables, the risk model has a higher diagnostic efficiency, with the area under the ROC being 0.699. Decision Curve Analysis (DCA) showed the prognostic model-based risk score was the superior prognostic factor compared to additional indicators. Furthermore, the high- and low-risk groups had differences in immune cell infiltration and immune functions. And the CCK-8 showed that small molecular drugs could inhibit HNSCC cell proliferation in vitro. We have constructed a new necroptosis-related model, which can be used to predict the prognosis and immunocompetence of HNSCC patients and provide a theoretical basis for the study of necroptosis in the clinical prognosis of HNSCC.

Peroxisome proliferator-activated receptors signature reveal the head and neck squamous cell carcinoma energy metabolism phenotype and clinical outcome.

Peroxisome proliferator activating receptors (PPARs) are important regulators of nuclear hormone receptor function, and they play a key role in biological processes such as lipid metabolism, inflammation and cell proliferation. However, their role in head and neck squamous cell carcinoma (HNSC) is unclear. We used multiple datasets, including TCGA-HNSC, GSE41613, GSE139324, PRJEB23709 and IMVigor, to perform a comprehensive analysis of PPAR-related genes in HNSC. Single-cell sequencing data were preprocessed using Seurat packets, and intercellular communication was analyzed using CellChat packets. Functional enrichment analysis of PPAR-related genes was performed using ClusterProfile and GSEA. Prognostic models were constructed using LASSO and Cox regression models, and immunohistochemical analyses were performed using human protein mapping (The Human Protein Atlas). Our single-cell RNA sequencing analysis revealed distinct cell populations in HNSC, with T cells having the most significant transcriptome differences between tumors and normal tissues. The PPAR features were higher in most cell types in tumor tissues compared with normal tissues. We identified 17 PPAR-associated differentially expressed genes between tumors and normal tissues. A prognostic model based on seven PPAR-associated genes was constructed with high accuracy in predicting 1, 2 and 3 year survival in patients with HNSC. In addition, patients with a low risk score had a higher immune score and a higher proportion of T cells, CD8+ T cells and cytotoxic lymphocytes. They also showed higher immune checkpoint gene expression, suggesting that they might benefit from immunotherapy. PPAR-related genes were found to be closely related to energy metabolism. Our study provides a comprehensive understanding of the role of PPAR related genes in HNSC. The identified PPAR features and constructed prognostic models may serve as potential biomarkers for HNSC prognosis and treatment response. In addition, our study found that PPAR-related genes can differentiate energy metabolism and distinguish energy metabolic heterogeneity in HNSC, providing new insights into the molecular mechanisms of HNSC progression and therapeutic response.

A comprehensive analysis of LINC00958 as a prognostic biomarker for head and neck squamous cell carcinoma

This work focused on exploring whether the long intergenic non-protein coding RNA LINC00958 is associated with the prognosis of head and neck squamous cell carcinoma (HNSCC). Associations of the LINC00958 expression level with clinicopathological features of HNSCC were investigated by logistic regression and Wilcoxon signed-rank test. The Kaplan–Meier method was applied to evaluate patient survival. Clinical data and expression profiles were obtained from The Cancer Genome Atlas (TCGA). Associations of patient clinical characteristics with overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) were assessed by univariate and multivariate analysis using the Cox proportional hazard model. Immune cell infiltration analysis and gene set enrichment analysis (GSEA) were applied to determine any significant effects of LINC00958. High LINC00958 expression was related to early pT stage (P < 0.01), primary therapy outcome (P < 0.01), HPV status (P < 0.001), lymphovascular invasion (P < 0.001), and perineural invasion (P < 0.01). The receiver operating characteristic curve showed strong prognostic power for LINC00958 (area under curve = 0.886). High LINC00958 expression predicted poor OS (P = 0.007), DSS (P = 0.036), and PFI (P = 0.040). LINC00958 was related to signalling pathways and the infiltration of certain immune cells. miR-27b-5p was significantly associated with LINC00958, and downstream NT5E predicted poor survival in HNSCC cases. LINC00958 may affect the prognosis by regulating NT5E via miR-27b-5p, and could serve as a possible factor to predict the prognosis of HNSCC, especially oral squamous cell carcinoma.

Potential Role of the Intratumoral Microbiota in Prognosis of Head and Neck Cancer.

The tumor microbiome, a relatively new research field, affects tumor progression through several mechanisms. The Cancer Microbiome Atlas (TCMA) database was recently published. In the present study, we used TCMA and The Cancer Genome Atlas and examined microbiome profiling in head and neck squamous cell carcinoma (HNSCC), the role of the intratumoral microbiota in the prognosis of HNSCC patients, and differentially expressed genes in tumor cells in relation to specific bacterial infections. We investigated 18 microbes at the genus level that differed between solid normal tissue (n = 22) and primary tumors (n = 154). The tissue microbiome profiles of Actinomyces, Fusobacterium, and Rothia at the genus level differed between the solid normal tissue and primary tumors of HNSCC patients. When the prognosis of groups with rates over and under the median for each microbe at the genus level was examined, rates for Leptotrichia which were over the median correlated with significantly higher overall survival rates. We then extracted 35 differentially expressed genes between the over- and under-the-median-for-Leptotrichia groups based on the criteria of >1.5 fold and p < 0.05 in the Mann-Whitney U-test. A pathway analysis showed that these Leptotrichia-related genes were associated with the pathways of Alzheimer disease, neurodegeneration-multiple diseases, prion disease, MAPK signaling, and PI3K-Akt signaling, while protein-protein interaction analysis revealed that these genes formed a dense network. In conclusion, probiotics and specific antimicrobial therapy targeting Leptotrichia may have an impact on the prognosis of HNSCC.