Head And Neck Squamous Cell Carcinoma Research Articles

The Use of Fluorescent Markers to Detect and Delineate Head and Neck Cancer: A Scoping Review.

The aim of surgery for head and neck squamous cell carcinoma (HNSCC) is to achieve clear resection margins, whilst preserving function and cosmesis. Fluorescent markers have demonstrated potential in the intraoperative visualisation and delineation of tumours, such as glioma, with consequent improvements in resection. The purpose of this scoping review was to identify and compare the fluorescent markers that have been used to detect and delineate HNSCC to date. A literature search was performed using the Ovid MEDLINE, Ovid Embase, Cochrane CENTRAL, ClinicalTrials.gov and ICTRP databases. Primary human studies published through September 2023 demonstrating the use of fluorescent markers to visualise HNSCC were selected and reviewed independently by two authors. The search strategy identified 5776 records. Two hundred and forty-four full texts were reviewed, and sixty-five eligible reports were included. The most used fluorescent markers in the included studies were indocyanine green (ICG) (n = 14), toluidine blue (n = 11), antibodies labelled with IRDye800CW (n = 10) and 5-aminolevulinic acid (5-ALA) (n = 8). Toluidine blue and ICG both have limited specificity, although novel targeted options derived from ICG may be more effective. 5-ALA has been demonstrated as a topical marker and, recently, via enteral administration but it is associated with photosensitivity reactions. The fluorescently labelled antibodies cetuximab-IRDye800CW and panitumumab-IRDye800CW are promising options being investigated by ongoing trials. Multiple safe fluorescent markers have emerged which may aid the surgical resection of HNSCC. Further research in larger cohorts is required to identify which marker should be considered gold standard.

Prognostic and diagnostic value of SPINK mRNAs expression in head and neck squamous cell carcinoma based on genome-wide analysis

Aim: Head and neck squamous cell carcinoma (HNSC) is a major contributor to the global cancer burden. The serine protease inhibitor Kazal-type (SPINK) gene family has been linked to various cancers. This study explores the prognostic value of SPINK genes in predicting overall survival (OS) in HNSC patients. Methods: We analyzed RNA sequencing and clinical data from 504 cancer and 44 non-cancer samples from the TCGA database. Differential expression and functional enrichment analyses gene ontology and Kyoto encyclopedia of genes and genomes (GO and KEGG) were performed using clusterProfiler. Protein-protein interaction (PPI) networks were built with STRING and visualized. Immune infiltration was evaluated using single-sample Gene Set Enrichment Analysis (ssGSEA). Survival analysis utilized Kaplan-Meier curves and Cox regression models. Results: Our results showed that SPINK5, SPINK7, SPINK8, SPINK9, and SPINK14 were significantly overexpressed in normal tissues compared to carcinoma tissues, whereas SPINK1, SPINK4, and SPINK6 showed higher expression in carcinoma tissues. Correlation analysis revealed significant relationships among SPINK family members. GO and KEGG analyses highlighted their involvement in processes such as negative regulation of peptidase activity and serine-type endopeptidase inhibitor activity. PPI network analysis indicated close interactions between several SPINK proteins and other relevant proteins. Immune infiltration analysis showed that NK cells and Th2 cells were negatively correlated with SPINK genes, while mast cells and neutrophils were positively correlated. Survival analysis revealed that high mRNA expression levels of SPINK1, SPINK5, and SPINK6 were significantly associated with OS in HNSC patients. Receiver operating characteristic (ROC) curve analysis indicated that these genes have diagnostic value. We developed a nomogram model that combines tumor stage and SPINK gene expression providing a predictive tool for patient prognosis. Conclusions: This study elucidates the multifaceted roles of the SPINK gene family in HNSC. These findings offer valuable insights into their potential as diagnostic biomarkers and therapeutic targets.

Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression

Interrogating regulatory epigenetic alterations during tumor progression at the resolution of single cells has remained an understudied area of research. Here we developed a highly sensitive single-nucleus CUT&RUN (snCUT&RUN) assay to profile histone modifications in isogenic primary, metastatic, and cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) patient-derived tumor cell lines. We find that the epigenome can be involved in diverse modes to contribute towards HNSCC progression. First, we demonstrate that gene expression changes during HNSCC progression can be comodulated by alterations in both copy number and chromatin activity, driving epigenetic rewiring of cell states. Furthermore, intratumour epigenetic heterogeneity (ITeH) may predispose subclonal populations within the primary tumour to adapt to selective pressures and foster the acquisition of malignant characteristics. In conclusion, snCUT&RUN serves as a valuable addition to the existing toolkit of single-cell epigenomic assays and can be used to dissect the functionality of the epigenome during cancer progression.

The role of super-enhancers in head and neck cancer and its potential therapeutic targets

Head and neck squamous cell carcinoma (HNSCC) poses a significant global health challenge, with over 660,000 new cases diagnosed and more than 325,000 deaths each year. Despite advances in treatment, long-term survival rates for HNSCC patients remain disappointingly low, underscoring the critical need for innovative therapeutic strategies. This review delves into the role of super-enhancers in HNSCC, highlighting their pivotal function in regulating key oncogenes such as KLF4, FOSL1, and ΔNp63, which are crucial for tumor progression and metastasis. Moreover, it explores how super-enhancers contribute to the maintenance of cancer stem cell characteristics by controlling genes like SOX2, BRD4. thereby promoting self-renewal and pluripotency.The study also underscores the potential of BET bromodomain inhibitors, exemplified by JQ1, and CDK7 inhibitors like THZ1, which demonstrate substantial therapeutic promise by effectively disrupting the function of super-enhancers in HNSCC. Overall, this research provides a comprehensive overview of the importance of super-enhancers in HNSCC .

Pembrolizumab (MK-3475) plus platinum and gemcitabine as first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (PIPER): a phase 2, multicentre, single-arm protocol study in Malaysia

IntroductionTreatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and...

Efficacy of 18FDG-PET/CT in Detecting Synchronous Malignancies in Patients With Head and Neck Cancer: A Systematic Review and Meta-analysis.

To assess the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (18FDG-PET/CT) in detecting second primary malignancies (SPMs) in patients with treatment naïve head and neck squamous cell carcinoma (HNSCC). Medline, Embase, Cochrane Library, and Scopus searched from 1946 to December 2022. Studies reporting the performance of 18FDG-PET/CT in patients with treatment-naïve, index HNSCC for detection of SPMs were included. The reference standard was histopathology, clinical follow-up over the duration of study, and other imaging modalities. Multiple investigators completed depth full-text analysis. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed. Methodologic and diagnostic accuracy data were abstracted independently by multiple investigators. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies tool independently. Bivariate random-effects model meta-analysis and multivariable meta-regression modeling were used. Seventeen studies examining 4624 patients with a total of 475 SPMs were included in the final analysis. Eleven studies were found to be at low risk for bias, while the rest were in the high-risk category. 18FDG-PET/CT demonstrated pooled sensitivity and specificity of 0.73 (95% confidence interval [CI]: 0.49-0.88) and 0.99 (95% CI: 0.98-1.00) in detecting SPMs. Further subsite analysis revealed varied diagnostic performance across different anatomical regions, with sensitivity and specificity of esophageal SPMs being 0.47 (0.30-0.64) and 0.99 (0.98-1.00), and sensitivity and specificity of 0.86 (0.73-0.94) and 0.99 (0.98-1.00) for head and neck SPMs. Finally, this imaging modality showed sensitivity and specificity of 0.92 (0.84-0.96) and 0.99 (0.98-1.00) for lung SPMs. The findings of this study suggest varied accuracy of 18FDG-PET/CT in detecting SPMs during initial workup for HNSCC, highlighting the importance of screening modalities such as esophagoscopy in high-risk patients.

RGIE: A Gene Selection Method Related to Radiotherapy Resistance in Head and Neck Squamous Cell Carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignant tumor with a high degree of malignancy, invasiveness, and metastasis rate. Radiotherapy, as an important adjuvant therapy for HNSCC, can reduce the postoperative recurrence rate and improve the survival rate. Identifying the genes related to HNSCC radiotherapy resistance (HNSCC-RR) is helpful in the search for potential therapeutic targets. However, identifying radiotherapy resistance-related genes from tens of thousands of genes is a challenging task. While interactions between genes are important for elucidating complex biological processes, the large number of genes makes the computation of gene interactions infeasible. We propose a gene selection algorithm, RGIE, which is based on ReliefF, Gene Network Inference with Ensemble of Trees (GENIE3) and Feature Elimination. ReliefF was used to select a feature subset that is discriminative for HNSCC-RR, GENIE3 constructed a gene regulatory network based on this subset to analyze the regulatory relationship among genes, and feature elimination was used to remove redundant and noisy features. Nine genes (SPAG1, FIGN, NUBPL, CHMP5, TCF7L2, COQ10B, BSDC1, ZFPM1, GRPEL1) were identified and used to identify HNSCC-RR, which achieved performances of 0.9730, 0.9679, 0.9767, and 0.9885 in terms of accuracy, precision, recall, and AUC, respectively. Finally, qRT-PCR validated the differential expression of the nine signature genes in cell lines (SCC9, SCC9-RR). RGIE is effective in screening genes related to HNSCC-RR. This approach may help guide clinical treatment modalities for patients and develop potential treatments.

Advances in the diagnosis and prognosis of extranodal extension in head and neck squamous cell carcinoma

Objective:The extranodal extension（ENE） is widely found in head and neck squamous cell carcinoma（HNSCC）, which displays the aggressiveness of the tumor and increasing the risk of local recurrence and distant metastasis, so the ENE often has been used as an important indicator of prognosis and treatment. Although the pathologic and radiologic tests are currently the main diagnostic techniques for ENE, there is still a lack of uniform standards. The article reviews the prognostic value, pathologic and radiologic diagnosis of ENE in HNSCC over the recent years.

Research progress on the role and mechanism of IGF2BPs family in head and neck squamous carcinoma

Objective:Head and neck squamous cell carcinoma（HNSCC） is one of the common malignant tumours, and most of them are in locally advanced stages at the time of diagnosis due to the lack of early symptoms, and the prognosis of such patients is still poor. M6A modification is the most common form of RNA modification in eukaryotic organisms, with a wide range of biological functions, and the family of IGF2BPs modulates growth, metastasis, chemotherapy resistance, and other processes of cancer by binding to and stabilizing a wide range of target RNAs through recognition of the m6A locus. The aim of this paper is to review the role and related mechanisms of IGF2BPs in head and neck squamous carcinoma, and to provide new ideas for early diagnosis and precision treatment of HNSCC.

Hypoxia regulates small extracellular vesicle biogenesis and cargo sorting through HIF-1α/HRS signaling pathway in head and neck squamous cell carcinoma

Small extracellular vesicles (sEVs) act as crucial messengers that transmit biological signals in hypoxic tumor microenvironments, significantly impacting cancer progression. However, the precise mechanism by which hypoxia influences sEV biogenesis remains poorly understood. In this study, we observed increased sEV secretion and alterations in cargo composition in head and neck squamous cell carcinoma (HNSCC) cells under hypoxic conditions. We found that hepatocyte growth factor–regulated tyrosine kinase substrate (HRS), a key component of the endosomal sorting complexes required for transport (ESCRT), was upregulated during hypoxia. This upregulation activated the endosomal system and reduced degradation of multivesicular bodies (MVBs). HRS depletion altered the packaging of protein cargoes such as mitochondria-related proteins into sEVs under hypoxia, and these cargoes promoted a pro-tumorigenic phenotype of macrophages. Importantly, we demonstrated that HRS is transcriptionally activated by hypoxia inducible factor-1α (HIF-1α). Spatial transcriptomics and immunohistochemistry revealed a positive correlation between HRS and HIF-1α. These findings establish a link between the hypoxic response, sEV biogenesis, and cargo packaging, enhancing our understanding of how the hypoxic tumor microenvironment influences sEV biogenesis in HNSCC cells.

LncRNA PVT1 promotes malignant progression by regulating the miR-7-5p/CDKL1 axis in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC), one of the most common types of head and neck squamous cell carcinoma (HNSCC), is characterized by high incidence and mortality. PVT1 is a long non-coding RNA (lncRNA) that plays an oncogenic role in various cancer types. This study aims to reveal the role and underlying molecular mechanism of PVT1 in OSCC progression. The expression levels of PVT1, miR-7-5p, and CDKL1 mRNA were evaluated using qRT-PCR. Western blot and IHC analysis were conducted to determine the protein expression of CDKL1. The biological functions of PVT1, miR-7-5p, and CDKL1 in OSCC were investigated through CCK-8, transwell migration and invasion assays. In vivo experiments utilized a xenograft model to examine the impact of PVT1 on OSCC. Furthermore, the interaction among PVT1, miR-7-5p, and CDKL1 was explored using RNA pull down assay and luciferase reporter assays. We found that PVT1 enhanced cell proliferation, migration, and invasion by targeting CDKL1. In addition, PVT1 functions as a sponge to modulate miR-7-5p, thereby influencing the expression of CDKL1 and the progression of OSCC. In conclusion, this study illustrates that the "PVT1/miR-7-5p/CDKL1" pathway is capable of promoting the progression of OSCC and may serve as a promising target for developing treatment strategies for OSCC.

Dynamic change of gut microbiota in head and neck concurrent chemoradiotherapy patients and its potential value in the prediction of acute oral mucositis grade as well as quality of life.

Radiotherapy is the major therapy for head and neck squamous cell carcinoma (HNSCC). However, whether gut microbiota changes in HNSCC patients who received concurrent chemoradiotherapy remains unclear. This study aimed to investigate the dynamic change of gut microbiota composition, construct the first radiotherapy-related gut microbiota database in these patients and identify the potential value of the gut microbiota changing in the prediction of acute oral mucositis grade as well as patients' life quality. We enrolled 47 HNSCC patients who scheduled with concurrent chemoradiotherapy. The field was irradiated with a total dose of 66-70Gy in 33-35 fractions. All the patients received 2-3 cycles of platinum-based chemotherapy. After feces specimens collected, bacterial genomic DNA was isolated using magnetic beads and then analyzed by the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene. 194 genera which belonged to 27 phyla were found in 141 samples. Increased abundance of microbiota in diversity and richness was observed in mid-radiotherapy group. Bacteroides, Blautia, Phascolarctobacterium were three main genera in all three groups and the mid-radiotherapy group had the highest relative abundance of Phascolarctobacterium. What is more, most significantly altered bacteria shared the same variation pattern which was increased in mid-radiotherapy while decreased to the almost same level of as pre-radiotherapy in post-radiotherapy group. Further analysis indicated that Bacteroidetes showing an upward trend while Proteobacteria declining in higher grade of acute mucositis. Moreover, relatively low abundant Proteobacteria was significantly correlated with high-grade acute oral mucositis. As for the quality of life, Lactobacillales and Actinomycetales were specifically found in better life quality group. However, Clostridia_UCG_014, Eubacteriaceae, UCG_010 and Moraxellaceae were unique abundantly present in worse life quality group. Chemoradiotherapy can affect the composition of the gut microbiota in HNSCC patients during the mid-term of treatment. Yet self-stabilized ability maintained the gut microbiota homeostasis. Dynamic change of specific species could help predict acute oral mucositis grade and characterize different quality of life group in these patients.

Massive parallel sequencing of head and neck conventional squamous cell carcinomas: A comprehensive review.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is a cause of significant mortality and morbidity. The epidemiology of this cancer varies worldwide due to either genetic differences in populations or differences in carcinogen exposure. The application of massive parallel sequencing-based techniques in HNSCC should provide a helpful understanding of the genetic alterations that eventually lead to HNSCC development and progression, and ideally, could be used for personalized therapy. In this review, the reader will find an overview of the mutational profile of conventional HNSCC according to published results on massive parallel sequencing data that confirm the pivotal role of TP53 and the frequent involvement of CDKN2A and PIK3CA. The reader will also find a more detailed description of the genes, such as NOTCH1 and FBXW7, that were not identified in HNSCCs before the development of these techniques, the differences that can be site-specific, such as the different mutational signatures that indicate specific carcinogens for various subsites of the head and neck, and finally, the actionability of these findings that should allow more personalized therapy for patients.

Lymph node density as prognostic factor in regional recurrent or residual head and neck cancer

Background Prognostic factors from neck dissection for regional recurrent or residual head and neck cancer remain undetermined. Aims/objectives We studied whether continuous variables from pathologic lymph nodes of salvage neck dissection could estimate survival outcomes in patients with head and neck squamous cell carcinomas (HNSCC). Materials and methods Pathologic continuous variables from neck dissection without primary tumor resection in 184 patients with HNSCC were retrospectively evaluated. Cutoff values from both lymph node density (LND) and log odds of positive lymph nodes (LODDS) as the variables were applied to death estimation. Uni-/multivariate survival analyses adjusting for pathologic N classification and extranodal extension were evaluated by log-rank test or Cox’s proportional hazard model, respectively. Results LND ≥ 0.14 and LODDS ≥ −1.72 were significantly related to univariate shorter survival outcomes. Multivariate analysis indicated a significant association between LND ≥ 0.14 and shorter overall (hazard ratio [HR] = 2.16, 95% confidence interval [CI] = 1.30–3.58), local recurrence-free (HR = 2.34, 95% CI = 1.06–5.16), regional recurrence-free (HR = 2.32, 95% CI = 1.27–4.25), and distant metastasis-free survival (HR = 2.17, 95% CI = 1.31–3.61). Conclusions and significance Based on the obtained results, increased LND was a poor prognostic factor following salvage neck dissection.

Phase 1/2 Study of the Aurora Kinase A Inhibitor Alisertib and Pembrolizumab in Refractory, Rb-Deficient Head and Neck Squamous Cell Carcinomas.

Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers. Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase 1) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase 2). The recommended phase 2 alisertib dose was 40 mg which had only the expected toxicity including cytopenia that led to dose reductions in two phase 2 patients at cycles 13 and 16. We saw no objective responses, but the combination led to prolonged stable disease (SD) in several patients, including 2 of 10 phase 1 patients (8 and 27 months). Eight of the 15 HPV-positive patients had SD; four of them (heavily pretreated) for ≥6 months, with median overall and progression-free survival durations of 16.8 and 1.4 months, respectively. In circulating immune cells and plasma patients with SD had markedly higher levels of HLA-DR-expressing natural killer cells than did progressive disease patients who demonstrated a more immunosuppressive and inflammatory profile. Pharmacokinetics did not indicate any significant drug-drug interactions between pembrolizumab and alisertib. The combination of alisertib and pembrolizumab was well tolerated and led to prolonged SD in some immunotherapy-resistant patients, supporting our hypothesis that Aurora kinase A inhibition can reverse immunotherapy resistance of retinoblastoma protein-deficient HNSCC.

Baş-Boyun Kanserlerinde Tek Merkez Setüksimab Deneyimi

"Exploring the Impact of Cetuximab in Head and Neck Cancers: Insights from a Single-Center Experience" Head and neck squamous cell carcinomas (HNSCC) are cancers originating from epithelial cells of the oral cavity, pharynx and larynx. It is known to be the seventh most common cancer worldwide. Approximately 5% of patients are diagnosed in the metastatic stage. Within the first 2 years; approximately 50-60% of patients who complete primary treatment returning with relapse. In our study, we aimed to evaluate the efficacy of Cetuximab, an anti-epidermal growth factor (EGFR) which used for recurrent unrezektabl or metastatic HNSCC. The study included 38 patients. 33 (86,8%) of them were male and 5 (13,2%) were female. Median age was 55,5 years. Mean follow-up period was 14,95±18,17 months. The median progression-free survival (PFS) of the patients was 4,6 months and the median overall survival (OS) was 7,1 months. We found shorter survival times compared to current literature studies. However the rate of metastatic patients and the rate of patients who had previously received chemotherapy were high in our study.

Frailty and Overall Survival of Older Patients Undergoing Radiotherapy for Head and Neck Cancer: A Prospective Analysis

Background/Objectives: Over 60% of diagnoses of head and neck squamous cell carcinoma (HNSCC) occur in patients aged over 65. The benefits of radiotherapy (RT) combined with chemotherapy remain controversial in geriatric patients. Frailty stratification is underutilized in clinical practice despite evidence suggesting its predictive power. We aimed to assess the impact of pre-treatment frailty stratification on overall survival (OS) and acute radiation-related toxicity in a cohort of older patients with HNSCC. Methods: A prospective cohort of 117 patients aged ≥65 years with newly diagnosed HNSCC was enrolled between 2017 and 2022. Patients received RT with or without chemotherapy. Frailty was assessed using the 40-item Frailty Index (FI) as part of a comprehensive geriatric assessment. The primary outcomes were OS and acute RT toxicity, defined as a grade ≥ 3 based on CTCAE 5.0. Cox proportional hazard models and logistic regression models, adjusted for age, tumor stage, and chemotherapy, were used. Results: After a median follow-up of 819 days, FI (HR 1.478, 95% CI 1.182–1.848, p < 0.001) was an independent predictor of OS. Grade ≥ 3 toxicities were observed in 38% of patients, but frailty was not significantly associated with toxicity. A sub-analysis of oropharyngeal carcinoma patients demonstrated improved OS in HPV-positive patients (HR 0.231, 95% CI 0.078–0.686, p = 0.008). Conclusions: the standardized introduction of frailty assessment in the evaluation of older HNSCC patients holds great promise for predicting long-term survival. This approach could be crucial in tailoring treatment protocols that account for the biological heterogeneity of older adults.

Effect of immortal time bias on the association between immune-related adverse events and oncological outcomes following immune checkpoint inhibitors therapy for head and neck squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) are pharmacological agents indicated for recurrent and metastatic head and neck squamous cell carcinoma (HNCSCC). Immune-related adverse events (irAEs) have been reported as predictors of therapeutic response to ICIs. However, previous studies have not adequately addressed the immortal time bias. Therefore, we aimed to investigate the association between the onset of irAEs and oncological outcomes, accounting for immortal time bias. We conducted a retrospective study involving 130 patients with HNSCC who were treated with ICIs. The objective response, progression-free survival (PFS), and overall survival (OS) were assessed using logistic regression analysis, the Kaplan-Meier method, and the Cox proportional hazard (PH) model. The immortal time bias was considered using a landmark analysis and an extended Cox (EC) model. The odds ratios for response and disease control were smaller in the landmark than in the naïve analyses. In the landmark analysis, the 1-year PFS rates were 47.6% and 27.2% for irAE+ and irAE- patients, respectively (p = 0.049), and the 1-year OS rates were 85.7% and 66.5%, respectively (p = 0.006). Regarding PFS, the adjusted HRs for irAEs were 0.49 (95% confidence interval (CI) 0.28-0.85) in the PH analysis and 0.75 (95% CI 0.40-1.40) in the EC analysis. As for OS, the adjusted HRs for irAEs were 0.36 (95% CI 0.19-0.66) in the PH analysis and 0.51 (95% CI 0.27-0.95) in the EC analysis. IrAEs were an independent prognostic factor for OS but not PFS. Without considering the immortal time bias, the association between irAEs and oncologic outcomes in patients with HNSCC treated with ICIs was overestimated. Therefore, the balance between the benefits and risks of ICI therapy must be carefully weighed in clinical settings.

TRIM47 promotes hypopharyngeal and laryngeal cancers progression through promoting K63-linked ubiquitination of vimentin.

Hypopharyngeal and laryngeal cancers which belong to head and neck squamous cell carcinoma (HNSCC) are the two most malignant types of head and neck cancer, characterized by a low 5-year survival rate, high recurrence and metastasis rate. It is vital to explore strategies to suppress metastasis and improve prognosis for patients with these cancers. In this research, we analyzed the clinical data and found that E3 ubiquitin ligase TRIM47 was upregulated in cancer tissues of hypopharyngeal cancer and was closely associated with poor survival outcomes. In terms of mechanism, we performed tandem affinity chromatography and denatured Ni-NTA Agarose pulldown. As a result, TRIM47 was found to interact with vimentin and control vimentin stabilization through ubiquitination, specifically in the form of K63 chains. Importantly, through experiments of cancer cell viability and migration, we found that TRIM47 could enhance the proliferation and metastasis abilities of cancer cells in a vimentin-dependent manner, thus promoting the advancement of hypopharyngeal and laryngeal cancers. TRIM47 was verified to regulate cancer cells metastasis invivo using metastasis models. All these results imply that TRIM47 emerges as a potential biomarker for early diagnosis and metastasis prediction of hypopharyngeal and laryngeal cancers and represents a promising therapeutic target.

N6-methyladenosine RNA modification in head and neck squamous cell carcinoma (HNSCC): current status and future insights.

N6-methyladenosine (m6A) plays a pivotal role in regulating epitranscriptomic mechanisms and is closely linked to the normal functioning of diverse classes of RNAs, both coding as well as noncoding. Recent research highlights the role of m6A RNA methylation in the onset and progression of several cancers, including head and neck squamous cell carcinoma (HNSCC). HNSCC ranks as the seventh most common cancer globally, with a five-year patient survival rate of just 50%. Elevated m6A RNA methylation levels and deregulated expression of various m6A modifiers, i.e. writers, readers, and erasers, have been reported across nearly all HNSCC subtypes. Numerous studies have demonstrated that m6A modifications significantly impact key hallmarks of HNSCC, such as proliferation, apoptosis, migration, and invasion. Furthermore, m6A impacts epithelial-mesenchymal transition (EMT), drug resistance, and aerobic glycolysis, and disrupts the tumor microenvironment. Additionally, transcripts regulated by m6A in HNSCC present themselves as potential diagnostic and prognostic biomarkers. This review attempts to comprehensively summarize the role of m6A RNA methylation and its modifiers in regulating various facets of HNSCC pathogenesis.