Head And Neck Squamous Cell Carcinoma Patients Research Articles

Construction of lysosome-related prognostic signature to predict the survival outcomes and selecting suitable drugs for patients with HNSCC.

Lysosomes are digestive organelles responsible for endocytosis and autophagy. Recently, the malignancy and invasiveness head and neck squamous cell carcinoma (HNSCC) has been increasingly studied with the role of lysosomes. A list of lysosome-related genes were obtained from MSigDB. A Spearman correlation and univariate Cox regression analyses combined with differential expression analysis were conducted to detect differentially expressed lysosome-related genes related to prognosis. The prediction of prognostic signature was evaluated by plotting survival curve, ROC, and by developing a nomogram. Immune subtypes, infiltration of immune cells, GSVA, TIDE, IC50 of common chemotherapy and targeted therapy, GO, and KEGG function enrichment analyses were carried out to explore the immune microenvironment of the signature. We constructed a lysosome-related prognostic signature that could function as an independent prognostic indicator for patients with HNSCC. High-risk patients were better suited to receive Doxorubicin, Mitomycin C, Pyrimethamine, anti-PD-L1 and anti-CTLA-4 immunotherapy, whereas low-risk patients had sensitivity to Lapatinib. GO functional enrichment analysis showed that prognostic features were strongly associated with epidermis-related functions (e.g., epidermal cell differentiation, epidermal development, and keratinization). In addition, a KEGG function enrichment analysis revealed a potential relationship between the risk assessment model and cardiomyopathy. We constructed a prognostic signature based on lysosome-related genes and successfully predicted the survival outcome of HNSCC patients, which not only provides potential guidance for personalized treatment but also provides a new idea for precision treatment of HNSCC.

XCT as a Predictor for Survival in a Population-Based Cohort of Head and Neck Squamous Cell Carcinoma.

xCT, also known as SLC7A11 (solute carrier Family 7 Member 11), is a cystine/glutamate antiporter protein that mediates regulated cell death and antioxidant defense. The aim of this study was to investigate the effect of xCT on the outcome of patients diagnosed with new head and neck squamous cell carcinoma (HNSCC). This retrospective cohort study utilized a population-based dataset, comprising all patients (n = 1033) diagnosed with new HNSCC during 2005-2015 in a population of 697,000 people. All patients (n = 585) with a tumor tissue sample available for immunohistochemical (IHC) staining were included. The follow-up rates were 97% and 81% at 3 and 5 years, respectively. Also, the specificity of the anti-xCT antibody was validated. The expression level and prognostic significance of xCT were strongly dependent on tumor location. In oropharyngeal squamous cell carcinoma (OPSCC) patients, xCT expression was a significant prognostic factor for 5-year overall survival (OAS) (HR: 2.71; 95% CI 1.67-4.39; p < 0.001), disease-specific survival (DSS) (HR: 2.58; 95% CI 1.47-4.54; p = 0.001), and disease-free survival (DFS) (HR: 2.69; 95% CI 1.55-4.64; p < 0.001). Five-year survival rates for OPSCC patients with high and low levels of xCT were OAS 34% versus 62%; DSS 51% versus 73%; DFS 43% versus 73%, respectively. According to a multivariate model adjusted for age, T-class, nodal positivity, and tobacco consumption, xCT was an independent prognostic factor for 3-year survival, in which it outperformed p16 IHC. Similar associations were not observed in squamous cell carcinomas of oral cavity or larynx. Regarding treatment modalities, xCT was most predictive in HNSCC patients who received radiotherapy. High xCT expression was associated with poor prognosis in OPSCC. Our findings suggest that joint analysis of xCT and p16 may add significant value in OPSCC treatment stratification.

Assessing the oral microbiome of head and neck cancer patients before and during radiotherapy.

To characterize the oral microbiome of patients with head and neck squamous cell carcinoma (HNSCC) before and during radiotherapy (RT), compared to healthy individuals. Evaluating the impact of oral microbiome in the clinical outcomes one year following the end of RT. Oral samples were collected from HNSCC patients who underwent RT using the following regimens: no dose received (T0), dose 12-16Gy (T1), dose 30-36Gy (T2) and dose ≥ 60Gy (T3). Samples from healthy individuals were also collected only once as a control group. Regions V1-V2 of the 16S rRNA were sequenced by Illumina and analyzed using Mothur. 49 patients with HNSCC and 25 healthy individuals were included. At T0, HNSCC patients showed a lower abundance of Firmicutes and Streptococcus (p = 0.011, p = 0.002) and a higher abundance of Bacteroidetes (p = 0.005) compared to healthy individuals. During RT, Fusobacterium (p = 0.017) and Porphyromonas (p = 0.0008) decreased, while Streptococcus increased at T1 (p = 0.001). By T3, the differences in Firmicutes, Bacteroidetes, and Streptococcus between the control and HNSCC groups were no longer significant (p > 0.3). Patients with higher initial abundances of Porphyromonas (p = 0.012) and Fusobacterium (p = 0.017) had poorer outcomes, including recurrence, metastasis, and death. In contrast, disease-free patients had a higher abundance of Streptococcus (p = 0.004). Oral microbiome dysbiosis was found in HNSCC patients. By the end of RT, the main initial differences in phylum and genus abundance observed at T0 between the control and HNSCC groups were no longer present. Higher abundances of Fusobacterium and Porphyromonas were associated with poor outcomes.

Glutamine and serum starvation alters the ATP production, oxidative stress, and abundance of mitochondrial RNAs in extracellular vesicles produced by cancer cells

Induction of autophagy represents an effective survival strategy for nutrient-deprived or stressed cancer cells. Autophagy contributes to the modulation of communication within the tumor microenvironment. Here, we conducted a study of the metabolic and signaling implications associated with autophagy induced by glutamine (Gln) and serum starvation and PI3K/mTOR inhibitor and autophagy inducer NVP-BEZ235 (BEZ) in the head and neck squamous cell carcinoma (HNSCC) cell line FaDu. We compared the effect of these different types of autophagy induction on ATP production, lipid peroxidation, mitophagy, RNA cargo of extracellular vesicles (EVs), and EVs-associated cytokine secretome of cancer cells. Both BEZ and starvation resulted in a decline in ATP production. Simultaneously, Gln starvation enhanced oxidative damage of cancer cells by lipid peroxidation. In starved cells, there was a discernible fragmentation of the mitochondrial network coupled with an increase in the presence of tumor susceptibility gene 101 (TSG101) on the mitochondrial membrane, indicative of the sorting of mitochondrial cargo into EVs. Consequently, the abundance of mitochondrial RNAs (mtRNAs) in EVs released by FaDu cells was enhanced. Notably, mtRNAs were also detectable in EVs isolated from the serum of both HNSCC patients and healthy controls. Starvation and BEZ reduced the production of EVs by cancer cells, yet the characteristic molecular profile of these EVs remained unchanged. We also found that alterations in the release of inflammatory cytokines constitute a principal response to autophagy induction. Importantly, the specific mechanism driving autophagy induction significantly influenced the composition of the EVs-associated cytokine secretome.

Feasibility analysis of using patient-derived tumour organoids for treatment decision guidance in locally advanced head and neck squamous cell carcinoma

BackgroundCurrent treatment for head and neck squamous cell carcinoma (HNSCC) involves surgery, radiotherapy, and chemotherapy. Despite aggressive multimodal approaches, tumour recurrence occurs in 40–60 % of cases, leading to poor survival outcomes. HNSCC lacks common genetic drivers for tailored therapies, and reliable biomarkers for treatment selection are scarce. We investigated the procedural requirements for incorporating drug- and radiosensitivity screens in patient-derived organoids (PDOs) within a clinical trial framework. Patients and methodsFresh tumour samples (N = 198) from 186 HNSCC patients were included. Success rates of organoid establishment were correlated with clinical and procedural parameters. Timelines for establishment of PDO cultures were determined, and their long-term growth potential assessed by serial passaging. Additionally, we conducted whole exome sequencing on matched tumour-organoid pairs. Three PDO models were employed to establish radiosensitivity assays. ResultsIn total, PDO models displaying histomorphological features and genomic alterations of parental tumours were successfully established for 35 % of patient tumours. Success rates rose to 77 % for samples with a tumour cell content of 30 % or higher. Advanced patient age, prior radiotherapy, and delays in tissue processing were identified as negative predictors for engraftment. The estimated time interval needed for screens was compatible with PDO-guided selection of curative-intent radiotherapy regimens. ConclusionsOur findings suggest that with high-quality samples and efficient tissue processing, PDO screens can be successfully performed in 77 % of HNSCC patients. Given the procedural challenges involved, future clinical trials aiming to the utility of PDOs for guiding treatment decisions should consider implementing centralised PDO screening.

Application of NRS2002 and PG-SGA in nutritional assessment for perioperative patients with head and neck squamous cell carcinoma: An observational study.

This study aimed to compare the effectiveness of 2 nutritional assessment tools, the Nutritional Risk Screening Scale 2002 (NRS2002) and the Patient-Generated Subjective Global Assessment (PG-SGA), for evaluating the nutritional status of perioperative head and neck squamous cell carcinoma (HNSCC) patients, to facilitate early nutritional interventions and improve clinical outcomes. An observational, comparative study was conducted at the Zhejiang Cancer Hospital, recruiting patients diagnosed with HNSCC scheduled for surgical treatment. The NRS2002 and PG-SGA were applied to assess patients' nutritional risk at multiple time points: upon admission, the day before surgery, 2 days after surgery, a week after surgery, and at discharge. Statistical analyses were performed using McNemar and Kappa tests to assess differences and consistency between NRS2002 and PG-SGA. A total of 209 patients were included in this study, predominantly male, with an average age of 60 years. Nutritional risk assessments identified an inverted "V" trend in nutritional risk, with the peak occurring 2 days post-surgery. PG-SGA consistently showed a higher screening positivity rate compared to NRS2002. The receiver operating characteristic curve analysis highlighted the discriminative power of both tools, with PG-SGA and NRS2002 showing high area under the curve values. Both NRS2002 and PG-SGA are effective for nutritional screening in HNSCC patients, with PG-SGA demonstrating a slightly higher sensitivity before surgery. PG-SGA may be more suitable for preoperative application, whereas NRS2002 is more appropriate for postoperative use.

Identification and validation of M2 macrophage-related gene signature as a novel prognostic model for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous tumor. Commonly used tumor staging don’t sufficiently and accurately assess the prognosis of HNSCC patients, resulting in a lack of guidance for clinical treatment decisions. M2 macrophage infiltration has been shown to be strongly associated with the tumor prognosis. In this study, we used the Cancer Genome Atlas (TCGA) data to screen for genes co-expressed with M2 macrophages in HNSCC. We used univariate Cox regression to screen out the genes associated with HNSCC prognosis, and constructed a HNSCC prognosis model by Lasso regression analysis. The results confirmed that the model had good predictive value and accuracy for the prognosis of HNSCC patients by survival analysis, ROC curve and nomogram. We divided the HNSCC samples into high-risk and low-risk groups according to the risk score, and the results showed that patients in the high-risk group were more prone to genetic mutations and had a higher tumor mutational burden. In addition, there were significant differences between risk groups in terms of immune cell infiltration and drug sensitivity. The HNSCC prognostic model established in this study may provide guidance for clinical therapeutic decision-making and provide a theoretical foundation for the development of new immunotherapy methods.

Prognosis prediction of head and neck squamous cell carcinoma through the basement membrane-related lncRNA risk model.

Head and neck squamous cell carcinoma (HNSCC) ranks among the most widespread and significantly heterogeneous malignant tumors globally. Increasing evidence suggests that the basement membrane (BM) and associated long non-coding RNAs (lncRNA) are correlated with the onset of HNSCC and its prognosis. Our study aims to construct a basement membrane-associated lncRNAs (BMlncRNAs) marker to accurately predict the prognosis of HNSCC patients and find novel immunotherapy targets. The Cancer Genome Atlas (TCGA) database was accessed to acquire the transcriptome expression matrices, somatic mutation data, and clinical follow-up data of HNSCC patients. Utilizing co-expression analysis, the BMlncRNAs were identified and the differentially expressed lncRNAs (DEBMlncRNA) were then filtered, The filtering thresholds are FDR<0.05 and |log2FC|≥1. Furthermore, univariate analysis, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression were utilized to develop the risk model. The model then underwent thorough evaluation across diverse perspectives, encompassing tumor immune infiltration, tumor mutation burden (TMB), functional enrichment, and chemotherapy sensitivity. The risk assessment model consists of 14 BMlncRNA pairs. The acquired data is indicative of the reliability of the risk score in its capacity as a prognostic factor. Individuals at high risk exhibited a poorer prognosis, and a statistically significant variance was noted in TMB and tumor immune infiltration compared to the low-risk group. Additionally, heightened sensitivity to paclitaxel and docetaxel was evident in the patients at high risk. We have established a BMLncRNA-based prognostic model that can provide clinical guidance for future laboratory and clinical studies of HNSCC.

Evaluating psychological distress in Chinese patients with head and neck squamous cell carcinoma planned for radiotherapy: a cross-sectional study using the distress thermometer.

We aim to estimate the prevalence of baseline clinically significant distress in Chinese patients with head and neck squamous cell carcinoma (HNSCC) before receiving the first radiotherapy and assess factors predictive of distress. One hundred and sixty-eight patients were enrolled to complete a set of questionnaires including Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS). Of these, 131 questionnaires were available for the final analysis. The accuracy of DT was validated using HADS as the gold standard, and receiver operating characteristic (ROC) curves were employed to identify the optimal cutoff score of DT. Distress was reported in sixty-two patients (47%). Patients who were visited in the last week (p = 0.022) and those with medical-related occupations (p = 0.017) were less likely to suffer from psychological distress. Additionally, religious belief was negatively associated with both the DT and HADS-T scores, indicating that patients with religious beliefs were less likely to report high levels of distress (odds ratio (OR) for DT ≥ 4 = 0.291, p = 0.039; OR for HADS-T ≥ 15 = 0.316, p = 0.047). Factors such as age, gender, marital status, education and residency did not contribute to distress levels. DT was significantly correlated with HADS-T (Correlation coefficient (r) = 0.624, p < 0.001) and the best cutoff score of DT was 4 in screening distress. DT was a brief and effective tool to screen distress among HNSCC patients.

KLF15 Transcription Activated Tachykinin Precursor 1 to Induce Perineural Invasion in Head and Neck Squamous Cell Carcinoma.

In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC). The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRTPCR. A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC. This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells.

Impact of immune-related adverse events on survival among patients with head-and-neck squamous cell carcinoma.

Aim: Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of metastatic head and neck squamous cell carcinomas (HNSCCs). Our goal was to assess for an association between immune-related adverse events (irAEs) and clinical outcomes for patients on ICIs.Methods: We analyzed a cohort of 110 HNSCC patients who received ICI therapy at the University of Virginia.Results: On review, 48% of our patients experienced an irAE with the most common events being hypothyroidism (30%), dermatitis (14%) and hepatitis (11%). Women were more likely to experience irAEs. Treatment interruption/discontinuation occurred in 43% patients with irAEs. Development of irAEs was associated with superior objective response rate (68 vs. 39%, p=0.009), with a greater rate of CR (17 vs. 5%) and PR (32vs. 16%). Twelve patients underwent ICI re-treatment following irAE, with 17% attaining a complete disease response, 25% attaining a partial response, 33% achieving stable disease and 25% experiencing disease progression with ICI resumption.Conclusion: Development of irAE was associated with superior objective response rate, with a greater rate of CR and PR. ICI re-treatment following irAE was feasible in a significant proportion of patients and can be attempted in carefully selected patients, given the dearth of second-line therapies for these patients.

Correlation of the treatment sensitivity of patient-derived organoids with treatment outcomes in patients with head and neck cancer (SOTO): protocol for a prospective observational study

IntroductionOrganoids have been successfully used in several areas of cancer research and large living biobanks of patient-derived organoids (PDOs) have been developed from various malignancies. The characteristics of the original...

From Bench to Bedside: A Team's Approach to Multidisciplinary Strategies to Combat Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is diagnosed in more than 71,000 patients each year in the United States, with nearly 16,000 associated deaths. One significant hurdle in the treatment of HNSCC is acquired and intrinsic resistance to existing therapeutic agents. Over the past several decades, the University of Wisconsin has formed a multidisciplinary team to move basic scientific discovery along the translational spectrum to impact the lives of HNSCC patients. In this review, we outline key discoveries made throughout the years at the University of Wisconsin to deepen our understanding of therapeutic resistance in HNSCC and how a strong, interdisciplinary team can make significant advances toward improving the lives of these patients by combatting resistance to established therapeutic modalities. We are profoundly grateful to the many scientific teams worldwide whose groundbreaking discoveries, alongside evolving clinical paradigms in head and neck oncology, have been instrumental in making our work possible.

Nuclear TOP1MT Confers Cisplatin Resistance via Pseudogene in HNSCC.

Cisplatin resistance is one of the major causes of treatment failure in head and neck squamous cell carcinoma (HNSCC). There is an urgent need to uncover the underlying mechanism for developing effective treatment strategies. A quantitative proteomics assay was used to identify differential proteins in cisplatin-resistant cells. Mitochondrial topoisomerase I (TOP1MT) localization was determined using laser confocal microscopy and nucleocytoplasmic separation assay. Chromatin immunoprecipitation sequencing, dual-luciferase reporter assay, and RNA immunoprecipitation were used to identify the interaction between pseudogenes, miRNAs, and real genes. In vivo experiments verified the interaction between TOP1MT and pseudogenes on cisplatin resistance. TOP1MT was identified as a driving factor of cisplatin resistance in vitro, in vivo, and in HNSCC patients. Moreover, TOP1MT exceptionally translocated to the nucleus in cisplatin-resistant HNSCC cells in a signal peptide-dependent manner. Nuclear TOP1MT (nTOP1MT) transcriptionally regulated the mitochondrial functional pseudogene MTATP6P1, which bound to miR-137 and miR-491-5p as a competing endogenous RNA (ceRNA) and promoted the expression of MTATP6. An increase in MTATP6 enhanced mitochondrial oxidative phosphorylation (OXPHOS), which conferred cisplatin resistance in HNSCC. Our findings revealed that nTOP1MT transcriptionally activated MTAPT6P1 and increased MTATP6 expression via ceRNA, which facilitated OXPHOS and cisplatin resistance. These results provide novel insight for overcoming cisplatin resistance in HNSCC.

Single cell analysis revealed SFRP2 cancer associated fibroblasts drive tumorigenesis in head and neck squamous cell carcinoma

Understanding the mechanisms of invasion and metastasis in head and neck squamous cell carcinoma (HNSCC) is crucial for effective treatment, particularly in metastatic cases. In this study, we analyzed multicenter bulk sequencing and comprehensive single-cell data from 702,446 cells, leading to the identification of a novel subtype of cancer-associated fibroblasts (CAFs), termed Secreted Frizzled-Related Protein2 CAFs (SFRP2_CAFs). These cells, originating from smooth muscle cells, display unique characteristics resembling both myofibroblastic CAFs and inflammatory CAFs, and are linked to poorer survival outcomes in HNSCC patients. Our findings reveal significant interactions between SFRP2_CAFs and SPP1 tumor-associated macrophages, which facilitate tumor invasion and metastasis. Moreover, our research identifies Nuclear factor I/X (NFIX) as a key transcription factor regulating SFRP2_CAFs behavior, confirmed through gene regulatory network analysis and simulation perturbation.

Phenotype remodelling of HNSCC cells in the muscle invasion environment

BackgroundTumour invading muscle in head and neck squamous cell carcinoma (HNSCC) is often associated with destructive growth and poor prognosis. However, the phenotypic functions and pathological mechanisms of muscle-invasive cancer cells in tumour progress remains unknown. In this study, we aimed to investigate the phenotypic functions of muscle-invasive cancer cells of HNSCC and their potential crosstalk with tumour microenvironment.MethodsWe obtained scRNA-seq data (SC) from GSE103322 (N = 18) and GSE181919 (N = 37), spatial RNA-seq data (ST) from GSE208253 and GSE181300 (N = 4), transcriptomics of human HNSCC samples from GSE42743 (N = 12) and GSE41613 (N = 97). Utilizing the TCGA-HNSC dataset, we conducted univariate and multivariate Cox analyses to investigate the prognostic impact of muscle-invasion in HNSCC, with validation in an additional cohort. Through Stutility and AUCell approaches, we identified and characterized muscle-invasive cancer cell clusters, including their functional phenotypes and gene-specific profiles. Integration of SC and ST data was achieved using Seurat analysis, multimodal intersection analysis, and spatial deconvolution. The results were further validated via in vitro and in vivo experiments.ResultsOur analyses of the TCGA-HNSC cohort revealed the presence of muscle-invasion was associated with a poor prognosis. By combining ST and SC, we identified muscle-invasive cancer cells exhibiting epithelial-to-mesenchymal transition (EMT) and myoepithelial-like transcriptional programs, which were correlated with a poor prognosis. Furthermore, we identified G0S2 as a novel marker of muscle-invasive malignant cells that potentially promotes EMT and the acquisition of myoepithelium-like phenotypes. These findings were validated through in vitro assays and chorioallantoic membranes experiments. Additionally, we demonstrated that G0S2-overexpressing cancer cells might attract human ECs via VEGF signalling. Subsequent in vitro and in vivo experiments revealed G0S2 plays key roles in promoting the proliferation and invasion of cancer cells.ConclusionsIn this study, we profiled the transcriptional programs of muscle-invasive HNSCC cell populations and characterized their EMT and myoepithelial-like phenotypes. Furthermore, our findings highlight the presence of muscle-invasion as a predictive marker for HNSCC patients. G0S2 as one of the markers of muscle-invasive cancer cells is involved in HNSCC intravasation, probably via VEGF signalling.

Novel Predictive Biomarkers in the Head and Neck Squamous Cell Carcinoma (HNSCC).

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, characterized by high aggressiveness and frequent metastasis to regional lymph nodes. Despite advances in therapy, including checkpoint inhibitor immunotherapy, surgery, radiotherapy, and chemotherapy, survival rates for patients with advanced HNSCC remain unsatisfactory. This article presents the latest research on predictive biomarkers such as PD-L1, PD-1, CTLA-4, p53, and HPV, which may enhance treatment efficacy and improve clinical outcomes for patients. The clinical value of these biomarkers, their limitations, and their potential application in HNSCC therapy are emphasized. Special attention is given to immunotherapy, which shows promising results in treating this type of cancer through the modulation of the immune response. The review's findings highlight the need for further research on new biomarkers to develop more personalized and effective therapeutic strategies for HNSCC patients.

The m6A and immune regulatory gene signature predicts the prognosis and correlates with immune infiltration of head and neck squamous cell carcinoma

Recent investigations have underscored the epigenetic modulation of the immune response; however, the interplay between RNA N6-methyladenosine (m6A) modification and immunomodulation in head and neck squamous cell carcinoma (HNSC) remains relatively unexplored. To bridge this knowledge gap, we undertook an extensive examination of the potential contributions of m6A modification and immunomodulation in HNSC. We amalgamated and deduplicated 27 m6A -related genes (m6AGs) and 1342 immune regulation-related genes (IMRGs), resulting in a comprehensive dataset encompassing 1358 genes. This dataset was scrutinized for m6A modification and immunomodulatory patterns within HNSC specimens. Employing Cox regression analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) technique, we developed a prognostic risk model for m6A regulator-mediated methylation modification and immunomodulation-related differentially expressed genes (m6A&IMRDEGs). Our differential expression analysis delineated 29 m6A&IMRDEGs, and Weighted Gene Co-expression Network Analysis (WGCNA) elucidated two module genes (IL11 and MMP13) subjected to correlation analysis. The prognostic prediction models revealed that the clinical predictive efficacy peaked for 1-year forecasts, followed sequentially by 3-year and 5-year predictions. The risk scores derived from the model adeptly categorized HNSC patients into high- and low-risk cohorts, with the high-risk group exhibiting a more unfavorable prognosis. Protein-Protein Interaction (PPI) analysis identified 7 hub genes implicated in m6A and immune regulation, namely BPIFB1, BPIFB2, GP2, MUC5B, MUC7, PIP, and SCGB3A1. Furthermore, we noted marked disparities in the expression profiles of 18 immune cell types between the high- and low-risk groups. Our results substantiate that the clustering subpopulations and risk models associated with m6A and immune regulatory genes portend a poor prognosis in HNSC. The risk score emerges as a potent prognostic biomarker and predictive metric for HNSC patients. A thorough assessment of m6A and immune regulatory genes in HNSC will augment our comprehension of the tumor immune microenvironment and facilitate the advancement of HNSC therapeutics.

Clinical relationships between the intratumoral microbiome and risk factors for head and neck cancer

A bioinformatic analysis is a promising approach to understand the relationship between the vast tumor microbiome and cancer development. In the present study, we studied the relationships between the intratumoral microbiome and classical clinical risk factors using bioinformatics analysis of the Cancer Genome Atlas (TCGA) and the Cancer Microbiome Atlas (TCMA) datasets involving HNSCC patients. We used TCMA database and investigated the abundance of microbes at the genus level in solid normal tissue (n=22) and the primary tumors of patients with head and neck squamous cell carcinoma (HNSCC) (n=154) and identified three major tumor microbiomes, Fusobacterium, Prevotella, and Streptococcus. The tissue level of Fusobacterium was higher in primary tumors than in solid normal tissue. However, univariate and multivariate analyses of these 3 microbes showed no significant effects on patient survival. We then extracted 43, 55, or 59 genes that were differentially expressed between the over and under the median groups for Fusobacterium, Prevotella, or Streptococcus using the criteria of >2.5, >1.5, or >2.0 fold and p<0.05 in the Mann-Whitney U-test. The results of a pathway analysis revealed the association of Fusobacterium- and Streptococcus-related genes with the IL-17 signaling pathway and Staphylococcus aureus infection, while Prevotella-associated pathways were not extracted. A protein-protein interaction analysis revealed a dense network in the order of Fusobacterium, Streptococcus, and Prevotella. An investigation of the relationships between the intratumoral microbiome and classical clinical risk factors showed that high levels of Fusobacterium were associated with a good prognosis in the absence of alcohol consumption and smoking, while high levels of Streptococcus were associated with a poor prognosis in the absence of alcohol consumption. In conclusion, intratumoral Fusobacterium and Streptococcus may affect the prognosis of patients with HNSCC, and their effects on HNSCC are modulated by the impact of drinking and smoking.

Inhibition of PNCK inflames tumor microenvironment and sensitizes head and neck squamous cell carcinoma to immune checkpoint inhibitors

BackgroundThe landscape of the tumor microenvironment (TME) is intricately linked to the development of head and neck squamous cell carcinoma (HNSCC) and significantly influences immunotherapy efficacy. Recent research has underscored...