Fibroblast activation protein (FAP) as a prognostic biomarker in multiple tumors and its therapeutic potential in head and neck squamous cell carcinoma

Background:Fibroblast activation protein(FAP),a cell surface serine protease,plays roles in tumor invasion and immune regulation.However,there is currently no pan-cancer analysis of FAP.Objective:We aimed to assess the pan-cancer expression profile of FAP,its molecular function,and its potential role in head and neck squamous cell carcinoma(HNSC).Methods:We analyzed gene expression,survival status,immune infiltration,and molecular functional pathways of FAP in The Cancer Genome Atlas(TCGA)and Genotype Tissue Expression(GTEx)tumors.Furthermore,to elucidate the role of FAP in HNSC,we performed proliferation,migration,and invasion assays post-FAP overexpression or knock-down.Results:FAP expression was elevated in nine tumor types and was associated with poor survival in eight of them.In the context of immune infiltration,FAP expression negatively correlated with CD8+T-cell infiltration infive tumor types and positively with regulatory T-cell infiltration in four tumor types.Our enrichment analysis highlighted FAP’s involvement in the PI3K-Akt signaling pathway.In HNSC cells,FAP overexpression activated the PI3K-Akt pathway,promoting tumor proliferation,migration,and invasion.Conversely,FAP knockdown showed inhibitory effects.Conclusion:Our study unveils the association of FAP with poor tumor prognosis across multiple cancers and highlights its potential as a therapeutic target in HNSC.

New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers worldwide.The main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma virus.Approved therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second primaries.The availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented pace.Initially,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk tumors.More recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within tumors.This review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

PPP1R14A is Associated with Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma Identified by Single-Cell and Bulk RNA-Sequencing

Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.

Bipolar hip arthroplasty using conjoined tendon preserving posterior lateral approach in treatment of displaced femoral neck fractures

BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective management option for these patients.Various approaches can be used for the BHA procedure.However,there is a high risk of postoperative dislocation.The conjoined tendon-preserving posterior(CPP)lateral approach was introduced to reduce postoperative dislocation rates.AIM To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients.METHODS We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA.The patients were followed up for at least 1 year.Among the 80 patients,57(71.3%)were female.The time to operation averaged 2.3 d(range:1-5 d).The mean age was 80.5 years(range:67-90 years),and the mean body mass index was 24.9 kg/m^(2)(range:17-36 kg/m^(2)).According to the Garden classification,42.5%of patients were typeⅢand 57.5%of patients were typeⅣ.Uncemented bipolar hip prostheses were used for all patients.Torn conjoined tendons,dislocations,and adverse complications during and after surgery were recorded.RESULTS The mean postoperative follow-up time was 15.3 months(range:12-18 months).The average surgery time was 52 min(range:40-70 min)with an average blood loss of 120 mL(range:80-320 mL).The transfusion rate was 10%(8 of 80 patients).The gemellus inferior was torn in 4 patients(5%),while it was difficult to identify in 2 patients(2.5%)during surgery.The posterior capsule was punctured by the fractured femoral neck in 3 patients,but the conjoined tendon and the piriformis tendon remained intact.No patients had stem varus greater than 3 degrees or femoral fracture.There were no patients with stem subsidence more than 5 mm at the last follow-up.No postoperative dislocations were observed throughout the follow-up period.No significance was found between preoperative and postoperative mean Health Service System scores(87.30±2.98 vs 86.10±6.10,t=1.89,P=0.063).CONCLUSION The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications.For surgeons familiar with the posterior lateral approach,there is no need for additional surgical instruments,and it does not increase surgical difficulty.

Complication rates after direct anterior vs posterior approach for hip hemiarthroplasty in elderly individuals with femoral neck fractures

BACKGROUND Dislocation rates after hemiarthroplasty reportedly vary from 1%to 17%.This serious complication is associated with increased morbidity and mortality rates.Approaches to this surgery are still debated,with no consensus regarding the superiority of any single approach.AIM To compare early postoperative complications after implementing the direct anterior and posterior approaches(PL)for hip hemiarthroplasty after femoral neck fractures.METHODS This is a comparative,retrospective,single-center cohort study conducted at a university hospital.Between March 2008 and December 2018,273 patients(a total of 280 hips)underwent bipolar hemiarthroplasties(n=280)for displaced femoral neck fractures using either the PL(n=171)or the minimally invasive direct anterior approach(DAA)(n=109).The choice of approach was related to the surgeons’practices;the implant types were similar and unrelated to the approach.Dislocation rates and other complications were reviewed after a minimum followup of 6 mo.RESULTS Both treatment groups had similarly aged patients(mean age:82 years),sex ratios,patient body mass indexes,and patient comorbidities.Surgical data(surgery delay time,operative time,and blood loss volume)did not differ significantly between the groups.The 30 d mortality rate was higher in the PL group(9.9%)than in the DAA group(3.7%),but the difference was not statistically significant(P=0.052).Among the one-month survivors,a significantly higher rate of dislocation was observed in the PL group(14/154;9.1%)than in the DAA group(0/105;0%)(P=0.002).Of the 14 patients with dislocation,8 underwent revision surgery for recurrent instability(posterior group),and one of them had 2 additional procedures due to a deep infection.The rate of other complications(e.g.,perioperative and early postoperative periprosthetic fractures and infection-related complications)did not differ significantly between the groups.CONCLUSION These findings suggest that the DAA to bipolar hemiarthroplasty for patients with femoral neck fractures is associated with a lower dislocation rate(<1%)than the PL.

Direct anterior compared to posterior approach for hip hemiarthroplasty following femoral neck fractures

The differences in complication rates between the direct anterior and posterior approaches for hemiarthroplasty in elderly patients with femoral neck fractures are not yet fully understood.Dislocation,a severe complication associated with increased mortality and often requiring additional surgery,may occur less frequently with the direct anterior approach compared to the posterior approach.Careful consideration of patient demographics is essential when planning the surgical approach.Future research in this area should focus on robust randomized controlled trials involving elderly patients recovering from femoral neck fractures.

Relationship between preoperative psychological stress and shortterm prognosis in elderly patients with femoral neck fracture

BACKGROUND Older adults are at high risk of femoral neck fractures(FNFs).Elderly patients face and adapt to significant psychological burdens,resulting in different degrees of psychological stress response.Total hip replacement is the preferred treatment for FNF in elderly patients;however,some patients have poor postoperative prognoses,and the underlying mechanism is unknown.We speculated that the postoperative prognosis of elderly patients with FNF may be related to preoperative psychological stress.AIM To explore the relationship between preoperative psychological stress and the short-term prognosis of elderly patients with FNF.METHODS In this retrospective analysis,the baseline data,preoperative 90-item Symptom Checklist score,and Harris score within 6 months of surgery of 120 elderly patients with FNF who underwent total hip arthroplasty were collected.We analyzed the indicators of poor short-term postoperative prognosis and the ability of the indicators to predict poor prognosis and compared the correlation between the indicators and the Harris score.RESULTS Anxiety,depression,garden classification of FNF,cause of fracture,FNF reduction quality,and length of hospital stay were independent influencing factors for poor short-term postoperative prognoses in elderly patients with FNF(P<0.05).The areas under the curve for anxiety,depression,and length of hospital stay were 0.742,0.854,and 0.749,respectively.The sensitivities of anxiety,depression,garden classification of FNF,and prediction of the cause of fracture were 0.857,0.786,0.821,and 0.821,respectively.The specificities of depression,FNF quality reduction,and length of hospital stay were the highest at 0.880,0.783,and 0.761,respectively.Anxiety,depression,and somatization scores correlated moderately with Harris scores(r=-0.523,-0.625,and-0.554;all P<0.001).CONCLUSION Preoperative anxiety,depression,and somatization are correlated with poor short-term prognosis in elderly patients with FNF and warrant consideration.

Classificatory updates in verrucous and cuniculatum carcinomas:Insights from the 5^(th) edition of WHO-IARC head and neck tumor classification

The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical insights.The 5th edition of the WHO/IARC classification of head and neck tumors refines the'Oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain histogenesis.Notably,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic factors.Noteworthy is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic characteristics.This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck.Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical relevance.By categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

Effect of Mouth Opening Training Stick Combined with Oral Massage on Mouth Opening Difficulty in Head and Neck Cancer Patients after Treatment

Objective: To study the application effect of mouth-opening training sticks combined with oral massage on patients with mouth-opening difficulty after treatment for head and neck cancer. Methods: Using convenient sampling, 60 patients with mouth-opening difficulty after treatment for head and neck cancer admitted to the Oncology Department from February 2022 to October 2023 were selected for a 2-week exercise and nursing program. The patients were divided into a control group (February 1, 2022 to November 30, 2022) and an observation group (December 1, 2022 to October 31, 2023), with 30 patients in each group. The control group underwent routine mouth-opening functional exercises combined with cork for oral support training, while the observation group underwent routine mouth-opening functional exercises combined with oral massage and mouth-opening training sticks for oral support training. The mouth-opening degree, mouth-opening difficulty level, comfort level, compliance, and quality of life were observed in both groups. Results: Before the intervention, there were no statistically significant differences in mouth-opening degree and mouth-opening difficulty level between the two groups (P > 0.05). After the intervention, the mouth-opening degree, mouth-opening difficulty level, oral comfort level, compliance, and QLICP-HN scores in the observation group were all better than those in the control group, with statistically significant differences (P < 0.05). Conclusion: The combination of mouth-opening training sticks and oral massage with mouth-opening functional exercises can effectively improve the degree of mouth-opening difficulty, enhance oral comfort, increase compliance with mouth-opening exercises, and improve quality of life.

Study on Electromyographic Characteristics of Neck Muscles in College Students with Chronic Neck Pain

Objective:To provide new insights for the evaluation and diagnosis of chronic neck pain(CNP).Methods:22 patients with CNP and 22 healthy individuals were recruited from South China Normal University,who were all college students.The subjects'neck extensor muscle strength in the head neutral position,the natural anteversion position,and the maximum forward flexion position were measured by an isometric muscle strength tester respectively.The neck extensor strength of CNP patients and healthy subjects were compared.Results:In the neutral position,the maximum isometric muscle strength of neck extensor muscles was 12.31 kg for CNP patients and 15.16 kg for healthy individuals,resulting in a ratio of 81%strength in patients compared to healthy subjects.This difference was highly significant(P<0.000).In the natural anteversion position,the respective values were 12.6 kg for CNP patients and 15.05 kg for healthy individuals,with a ratio of 83%,and a significant difference between groups(P<0.001).In the maximum forward flexion position of the head,the values were 13.36 kg for CNP patients and 16.15 kg for healthy individuals,with a ratio of 82%,and a highly significant difference(P<0.000).Conclusion:The neck extensor muscle strength levels in college students with CNP were significantly lower compared to healthy college students across all measured positions.

Application of single-cell RNA sequencing in head and neck squamous cell carcinoma

Single-cell RNA sequencing has been broadly applied to head and neck squamous cell carcinoma(HNSCC) for characterizing the heterogeneity and genomic mutations of HNSCC benefiting from the advantage of single-cell resolution. We summarized most of the current studies and aimed to explore their research methods and ideas, as well as how to transform them into clinical applications. Through single-cell RNA sequencing, we found the differences in tumor cells’ expression programs and differentiation tracks. The studies of immune microenvironment allowed us to distinguish immune cell subpopulations, the extensive expression of immune checkpoints, and the complex crosstalk network between immune cells and non-immune cells. For cancerassociated fibroblasts(CAFs), single-cell RNA sequencing had made an irreplaceable contribution to the exploration of their differentiation status, specific CAFs markers, and the interaction with tumor cells and immune cells. In addition, we demonstrated in detail how single-cell RNA sequencing explored the HNSCC epithelial-tomesenchymal transition(EMT) model and the mechanism of drug resistance, as well as its clinical value.

Role of prophylactic central neck lymph node dissection for papillary thyroid carcinoma in the era of de-escalation

Thyroid cancer is the most common endocrine malignancy.While there has been no appreciable increase in the observed mortality of well-differentiated thyroid cancer,there has been an overall rise in its incidence worldwide over the last few decades.Patients with papillary thyroid carcinoma(PTC)and clinical evidence of central(cN1)and/or lateral lymph node metastases require total thyroidectomy plus central and/or lateral neck dissection as the initial surgical treatment.Nodal status in PTC patients plays a crucial role in the prognostic evaluation of the recurrence risk.The 2015 guidelines of the American Thyroid Association(ATA)have more accurately determined the indications for therapeutic central and lateral lymph node dissection.However,prophylactic central neck lymph node dissection(pCND)in negative lymph node(cN0)PTC patients is controversial,as the 2009 ATA guidelines recommended that CND“should be considered”routinely in patients who underwent total thyroidectomy for PTC.Although the current guidelines show clear indications for therapeutic CND,the role of pCND in cN0 patients with PTC is still debated.In small solitary papillary carcinoma(T1,T2),pCND is not recommended unless there are high-risk prediction factors for recurrence and diffuse nodal spread(extrathyroid extension,mutation in the BRAF gene).pCND can be considered in cN0 disease with advanced primary tumors(T3 or T4)or clinical lateral neck disease(cN1b)or for staging and treatment planning purposes.The role of the preoperative evaluation is fundamental to minimizing the possible detrimental effect of overtreatment of the types of patients who are associated with low disease-related morbidity and mortality.On the other hand,it determines the choice of appropriate treatment and determines if close monitoring of patients at a higher risk is needed.Thus,pCND is currently recommended for T3 and T4 tumors but not for T1 and T2 tumors without high-risk prediction factors of recurrence.

Resolving Specific Psychological Stressors Can Instantly Reduce or Relieve Chronic Neck Pain and Upper Back Pain: Case Reports

Introduction: The goal of this study was to use a novel approach to pain relief which includes a participant using their mind to reduce or relieve their neck pain in a matter of minutes and taking continuous thermal medical imaging scans during the process to capture any concurrent temperature changes at the location of the self-reported pain. Previous studies using multidisciplinary approaches have shown that it is possible for a person to achieve a moderate reduction in pain over a period of time (typically two or more months). However, in this innovative study, the goal was to demonstrate rapid pain relief (in a matter of minutes) using only the mind. Case report: For this study, six subjects were selected, all of whom were experiencing long-term chronic neck pain. The subjects consisted of five adult females and one adult male. Several of the subjects also had pain that radiated into their upper back region. Each subject participated in one talk therapy session during which the subject’s neck was actively scanned by a thermal imaging (TI) camera that was programmed to take a new thermal image every thirty (30) seconds. The goal of the talk therapy session was to create a strong emotional shift by encouraging the subject to let go of negative emotions and replace buried painful feelings with feelings of positive expectation and optimism. Then, as the subject created this emotional shift, the goal was to observe if this change affected the subject’s self-reported physical pain, as well as noting any visible effects in thermal images. Results: All six subjects reported that they were able to relieve some or all of their pain by the end of the talk therapy session. As they did, there was simultaneously a significant decrease in temperature recorded on the TI images in the corresponding location in their neck and upper back region. This suggested that the pain relief the subjects reported was not merely “mind over matter”, since there were marked physiological changes taking place. Discussion and Conclusion: It’s worth noting that three of the subjects had moments during their talk therapy session where they thought about a specific painful memory that increased their negative emotions. At that moment, their self-reported pain also increased, and simultaneously, the infrared camera detected an increase in temperature in the corresponding location where the subjects reported increased pain. Subsequently, when the subjects were able to change the painful memory and once again move towards feelings of optimism, they reported pain relief, and simultaneously, the TI camera reported a decrease in temperature. Neither this potential outcome nor any other potential outcome was discussed with the subjects before or during the session. This research shows that talk therapy may be used as a new therapeutic option for people not only with neck pain, but possibly other types of pain, and that under certain circumstances, the results can be rapid.

Magnetic resonance imaging evaluation of head and neck involvement in IgG4-related disease

Objective:To evaluate the radiological features of IgG4-related disease(IgG4-RD)in the head and neck region.Methods:In this radiology-based study,radiological features,clinical,laboratory,pathological findings,and prognosis of nine patients with head and neck involvement diagnosed with IgG4-RD were investigated retrospectively.Results:The median age of the patients was 38 years(range:2.5-79 years),and there were six males and three females.The most common symptoms and clinical findings of the patients were eyelid and lacrimal gland swelling,painless exophthalmos,and ophthalmoplegia.The most common site of involvement on MRI was the orbit.Orbital involvement was followed by branches of the trigeminal nerve,sinonasal cavity,cervical lymph nodes,and dural involvement.The most common and remarkable imaging features were T2 hypointensity and diffuse homogeneous contrast enhancement.Conclusions:Head and neck involvement of the IgG4-RD,has specific imaging features that can help with diagnosis.Thus,early diagnosis and better outcomes can be achieved with increasing awareness of these features of this relatively new pathology.

Safety and Efficacy of Endovascular Aortic Repair for Abdominal Aortic Aneurysms with a Hostile Neck Anatomy

Objective This study aimed to investigate the safety and efficacy of endovascular aortic repair(EVAR)for the treatment of an abdominal aortic aneurysm(AAA)with a hostile neck anatomy(HNA).Methods From January 1,2015 to December 31,2019,a total of 259 patients diagnosed with an AAA who underwent EVAR were recruited into this study.Based on the morphological characteristics of the proximal neck anatomy,the patients were divided into the HNA group and the friendly neck anatomy(FNA)group.The patients were followed up for up to 4 years.Results The average follow-up time was 1056.1±535.5 days.Type I endoleak occurred in 4 patients in the HNA group,and 2 patients in the FNA group.Neither death nor intraoperative switch to open repair occurred in either group.The time of the operation was significantly longer in the HNA group(FNA vs.HNA,99.2±51.1 min vs.117.5±63.8 min,P=0.011).There were no significant differences in short-term clinical success rate(P=0.228)or midterm clinical success rate(P=0.889)between the two groups.The overall mortality rate was 10.4%,and Kaplan-Meier survival analysis indicated that the two groups had similar cumulative survival rates at the end of the follow-up period(P=0.889).Conclusion EVAR was feasible and safe in patients with an AAA with a proximal HNA.The early and midterm results were promising;however,further studies are needed to verify the long-term effectiveness of EVAR.

Glucocorticoid reduces the efficacy of afatinib on the head and neck squamous cell carcinoma

Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal growth factor receptor(EGFR)-targeted therapy of head and neck squamous cell carcinoma(HNSCC)remaining to be elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC cell lines(HSC-3,SCC-25,SCC-9,and H-400)and the human oral keratinocyte(HOK)cell lines were assessed for GC receptor(GR)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.

Comprehensive bioinformatics analysis and experimental validation:An anoikis-related gene prognostic model for targeted drug development in head and neck squamous cell carcinoma

We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of anoikis-related genes(ARGs)in HNSCC and develop new targeted drugs.Differentially expressed ARGs were screened using bioinformatics methods;subsequently,a prognostic model including three ARGs(CDKN2A,BIRC5,and PLAU)was constructed.Our results showed that the model-based risk score was a good prognostic indicator,and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database,the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus database.Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database.Finally,in vitro experiments were used to verify the database findings.The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results.BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells.Molecular docking,real-time PCR,cell counting kit-8(CCK-8),plate clone,and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model,inhibit HNSCC cells survival rate,and promote anoikis in vitro.Therefore,we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC,paving the way for clinically targeting anoikis in HNSCC.

Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model,cellular platform,and clinical human data

Head and neck squamous cell cancer(HNSCC)is a leading global malignancy.Every year,More than 830000 people are diagnosed with HNSCC globally,with more than 430000 fatalities.HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics.It originates from the squamous epithelium of the oral cavity,oropharynx,nasopharynx,larynx,and hypopharynx.The most frequently impacted regions are the tongue and larynx.Previous investigations have demonstrated the critical role of host genetic susceptibility in the progression of HNSCC.Despite the advances in our knowledge,the improved survival rate of HNSCC patients over the last 40 years has been limited.Failure to identify the molecular origins of development of HNSCC and the genetic basis of the disease and its biological heterogeneity impedes the development of new therapeutic methods.These results indicate a need to identify more genetic factors underlying this complex disease,which can be better used in early detection and prevention strategies.The lack of reliable animal models to investigate the underlying molecular processes is one of the most significant barriers to understanding HNSCC tumors.In this report,we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes(e.g.Smad 4 and P53 genes)to identify genetic factors affecting the development of this complex disease using genome-wide association studies,epigenetics,micro RNA,long noncoding RNA,lnc RNA,histone modifications,methylation,phosphorylation,and proteomics.

Reconstruction surgery in head and neck cancer patients amidst the COVID-19 pandemic:Current practice and lessons for the future

The coronavirus disease 2019(COVID-19)pandemic has imposed a radical change in daily life and work routine.In this context,health systems have suffered important and serious repercussions in all fields.Among the changes brought about by the state of global health emergency,adjustments to guidelines,priorities,structures,professional teams,and epidemiological data stand out.In light of this,the oncological field has witnessed several changes in the approach to cancer,whether due to delay in diagnosis,screening deficit,personnel shortage or the psychological impact that the pandemic has had on cancer patients.This article focuses on the management of oral carcinoma and the surgical approaches that oral and maxillofacial specialists have had at their disposal during the health emergency.In this period,the oral and maxillofacial surgeons have faced many obstacles.The proximity of maxillofacial structures to the airways,the need of elective and punctual procedures in cancerous lesions,the aggressiveness of head and neck tumors,and the need for important healthcare costs to support such delicate surgeries are examples of some of the challenges imposed for this field.One of the possible surgical'solutions'to the difficulties in managing surgical cases of oral carcinoma during the pandemic is locoregional flaps,which in the pre-COVID-19 era were less used than free flaps.However,during the health emergency,its use has been widely reassessed.This setback may represent a precedent for opening up new reflections.In the course of a long-term pandemic,a reassessment of the validity of different medical and surgical therapeutic approaches should be considered.Finally,given that the pandemic has highlighted vulnerabilities and shortcomings in a number of ways,including the issues of essential resource shortages,underinvestment in public health services,lack of coordination and versatility among politicians,policymakers and health leaders,resulting in overloaded health systems,rapid case development,and high mortality,a more careful analysis of the changes needed in different health systems to satisfactorily face future emergencies is essential to be carried out.This should be directed especially towards improving the management of health systems,their coordination as well as reviewing related practices,even in the surgical field.

A pilot study of the relative number of circulating tumor cells and leukocytes containing actin-binding proteins in head and neck cancer patients

Circulating tumor cells(CTCs)play an important role in tumor metastases,which is positively correlated with an increased risk of death.Actin-binding proteins,including cofilin(CFL1),profilin 1(PFN1),and adenylate cyclase-associated protein 1(CAP1),are thought to be involved in tumor cell motility and metastasis,specifically in head and neck squamous cell carcinoma(HNSCC).However,currently,there are no published studies on CFL1,PFN1,and CAP1 in CTCs and leukocytes in HNSCC patients.We assessed serum levels of CFL1,PFN1,and CAP1 and the number of CTCs and leukocytes containing these proteins in blood from 31 HNSCC patients(T1-4N0-2M0).The analysis used flow cytometry and an enzyme-linked immunosorbent assay kit.We found that CAP1+CTCs and CAP1+leukocyte subpopulations were prevalent in these HNSCC patient samples,while the prevalence rates of CFL1+and PFN1+CTCs were relatively low.Patients with stage T2-4N1-2M0 had CFL1+and PFN1+CTCs with an elevated PFN1 serum level,compared with the T1-3N0M0 group.In summary,the PFN1 serum level and the relative number of PFN1+CD326+CTCs could be valuable prognostic markers for HNSCC metastases.The current study is the first to obtain data regarding the contents of actin-binding proteins(ABPs)in CTCs,and leukocytes in blood from HNSCC patients.This is also the first to assess the relationship between the number of CTCs subgroups and disease characteristics.