Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) acts as a pivotal molecular chaperone in oncogenesis, yet its precise role in head and neck squamous cell carcinoma (HNSC) remains unclear. This study integrated bioinformatics with experimental validation to elucidate the expression, prognostic value, and immunological implications of HSP90AA1 in HNSC. Transcriptional profiling using The Cancer Genome Atlas (TCGA) revealed pronounced HSP90AA1 upregulation, which was confirmed by immunohistochemistry (IHC). Kaplan-Meier and Cox regression analyses identified high HSP90AA1 expression as an independent adverse prognostic factor. Furthermore, computational immune infiltration analyses demonstrated that HSP90AA1 levels significantly correlate with altered tumor microenvironment (TME) immune architecture. These findings indicate that HSP90AA1 is a critical biomarker for HNSC, offering substantial potential for diagnosis, prognosis, and predicting immunotherapeutic efficacy.

Laryngeal cancer invasion and metastasis, the primary causes of mortality, have generated a vast scientific knowledge base. This study employs bibliometrics to decode this intellectual landscape, mapping its evolutionary structure and identifying pivotal collaborations. Based on 3866 publications retrieved from the Web of Science Core Collection (1996-2025), a comprehensive visual analysis was conducted using VOSviewer and COOC. The results reveal a robust upward trend in scholarly output, with China emerging as the dominant contributor. Fudan University, Harbin Medical University, and Sun Yat-sen University led in publication volume, while network analysis identified Harbin Medical University and the Chinese Academy of Medical Sciences as central collaborative hubs. Thematically, research has concentrated on "Prognosis," "Radiotherapy," and "Neck Dissection," forming distinct, specialized clusters. In conclusion, this bibliometric analysis reveals a China-led surge in research driven by key clinical themes. However, the field is characterized by specialized clusters rather than a fully integrated network. Future progress requires fostering synergistic global collaborations to bridge these thematic divides and accelerate clinical translation.

To establish consensus recommendations and standardized protocols for the clinical assessment and management of radiation-induced hearing loss (RIHL), a common yet potentially serious complication in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy, for which effective treatments remain limited. A two-round Delphi survey was conducted with 19 Chinese experts from diverse specialties, including radiation oncology, medical oncology, radiology, and otorhinolaryngology. Utilizing a detailed items questionnaire that addressed diagnosis, prevention, and treatment aspects of RIHL, the panel formulated consensus recommendations. Additionally, the final recommendations were formulated based on the findings of the Delphi survey, in conjunction with evidence appraised using the GRADE system. During radiotherapy planning, the implementation of dose constraints for key auditory structures—namely the tympanic cavity, internal auditory canal and cochlea—was emphasized to preserve auditory function. Diagnostic evaluations were advised to comprise comprehensive assessments such as pure tone and speech audiometry, tympanometry, otoacoustic emissions, auditory evoked potentials, otoscopic examination, and CT/MRI imaging, with classification guided by the 2021 WHO grading criteria for type and severity. Therapeutic approaches should be customized based on disease stage and underlying etiology, incorporating strategies like Eustachian tube function restoration, management of otitis media with effusion, and tailored auditory rehabilitation. However, consensus on the applicability of most interventions was limited due to insufficient or conflicting evidence, underscoring the need for further research. This consensus provides a structured framework to standardize clinical assessment and management of RIHL, while laying a groundwork for future studies focused on optimizing patient outcomes.

Head and neck squamous cell carcinoma (HNSCC) exhibits a poor prognosis, with 5-year survival rates below 50%. This study employed network pharmacology to investigate the anti-HNSCC mechanism of silibinin, a plant-derived compound with established anticancer activity. We obtained potential silibinin targets from pharmacological databases and HNSCC-associated targets from TCGA. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to identify critical pathways and biological processes. Through protein-protein interaction (PPI) network screening, we selected hub genes for molecular docking validation. We evaluated silibinin's effects on HNSCC proliferation and invasion using CCK-8 assays, colony formation tests, and cell invasion experiments. Our data suggested that silibinin may inhibit HNSCC progression through modulation of the interleukin-17 signaling pathway. Molecular docking confirmed strong binding affinity between silibinin and key targets, supporting its potential as an HNSCC therapeutic agent.

Nicotine, which is enriched in tobacco, has been identified as an important factor in the development of oral cancer. The natural flavonoid quercetin has potential anti-tumor properties due to its low toxicity and high efficacy. We aimed to explore the potential molecular targets of quercetin for the treatment of nicotine-related oral cancer by network pharmacological analysis and to evaluate its efficacy in vitro experiments. A total of 29 potential target genes were identified, which may be associated with epithelial-mesenchymal transition (EMT), the receptor tyrosine kinase (RTK) pathway, and immune cell infiltration, as well as acquired resistance to various chemotherapeutic agents. Molecular docking and molecular dynamics simulation indicated that quercetin may bind more strongly to potential key genes (THBS1, SERPINE1, and IGF1R). Quercetin was shown to affect key gene expressions in nicotine-related oral cancer cells and attenuate their malignant phenotype in vitro experiments. A series of novel targets for quercetin in the treatment of nicotine-related oral cancer were identified. These findings not only help understand the pathogenesis of oral cancer but also help explore its precancerous preventive measures, which are of great value for oral cancer prevention.

Papillary thyroid carcinoma (PTC) is the most common type of endocrine tumor, and its incidence is on the rise. Observational studies have linked cathepsins, an endolysosomal cysteine protein hydrolase, to the malignant progression of several tumors, including PTC. However, the causal relationship between cathepsins and PTC remains unclear. The purpose of this study was to investigate the causal relationship between cathepsins and PTC using a bidirectional two-sample Mendelian randomization (MR) analysis. Publicly available databases were used to obtain data on cathepsins and PTCs. Single nucleotide polymorphisms were screened for instrumental variables. Causality was evaluated using five methods. Heterogeneity and sensitivity analyses were performed to evaluate the stability of the results. The analysis revealed a significant association between cathepsin Z (CTSZ) and the risk of PTC (IVW, OR = 1.170, 95

Introduction The aim of this study was to explore the causal relationship between telomere length and Oral and oropharyngeal cancers by using Mendelian randomization (MR) analysis. Methods We carried out a 2-sample MR to examine the causal association between telomere length and Oral and oropharyngeal cancers. Two large genome-wide association studies (GWAS) were employed to identify single nucleotide polymorphisms (SNPs) as instrumental variables through statistical and biological approaches. The data on SNP-oral and oropharyngeal cancer risk factor associations were sourced from various consortia/UK Biobank. The inverse variance weighted (IVW) method was employed as the primary approach for overall causal estimation in MR, with sensitivity analyses conducted to assess potential confounding by pleiotropy, heterogeneity, and the leave-one-out analysis. Results The statistically driven approach indicates limited evidence of a genetically causal effect of telomere length on the risk of oral cavity cancer (OR = 0.999, 95% CI 0.998-1.000, P = .100), oropharyngeal cancer (OR = 0.999, 95% CI 0.998-1.001, P = .650), combined oral and oropharyngeal cancer (OR = 0.999, 95% CI 0.998-1.000, P = .119) in Europeans. The biologically driven approach demonstrated consistent causal effects across all MR methods, thereby further strengthening the reliability of the results. Moreover, the MR-Egger (Q [df] 170.816 [130], P = .009) and inverse variance weighted methods (Q [df] 171.656 [131], P = .010) identified considerable heterogeneity among instrumental variable estimates in Oral cavity cancer, and no evidence of horizontal pleiotropy was detected. Conclusions No significant causal associations between telomere length and Oral and oropharyngeal cancers were found in this study.

BACKGROUND:C-C motif chemokine ligand 3 (CCL3) is a crucial chemokine that plays a fundamental role in the immune microenvironment and is closely linked to the development of various cancers. Despite its importance, there is limited research regarding the expression and function of CCL3 in nasopharyngeal carcinoma (NPC). Therefore, this study seeks to examine the expression of CCL3 and assess its clinical significance in NPC using bioinformatics analysis and experiments. METHODS:The bioinformatics approach was employed to assess the expression and function of CCL3 in NPC. Subsequently, protein expression of CCL3 was detected in an NPC cohort using immunohistochemistry based on a tissue microarray. The relationship between CCL3 expression and clinical features was then investigated. RESULTS:A total of 20 CCL3-related genes and 14 possible target genes were identified through bioinformatics analysis, many of which play crucial roles in pathways such as chemokine signaling pathway and transcriptional misregulation in cancer signaling pathways. CCL3 was found to be associated with drug resistance and various immune cell infiltrations. In NPC, CCL3 expression was significantly higher than normal controls, and high expression of CCL3 correlated with cervical lymph node metastasis, tumor recurrence, advanced clinical stage, and poor prognosis. CONCLUSIONS:CCL3 may be a key gene in the initiation and progression of NPC. It has the potential to serve as both a diagnostic biomarker and a therapeutic target for NPC.

Objective Angiogenesis-associated genes (AAGs) play a critical role in cancer patient survival. However, there are insufficient reports on the prognostic value of AAGs in head and neck squamous cell carcinoma (HNSC). Therefore, this study aimed to investigate the correlation between AAG expression levels and survival in HNSC patients, explore the predictive value of signature genes and lay the groundwork for future in-depth research. Methods Relevant data for HNSC were obtained from the databases. AAGs-associated signature genes linked to prognosis were screened to construct a predictive model. Further analysis was conducted to determine the functional correlation of the signature genes. Results The signature genes (STC1, SERPINA5, APP, OLR1, and PDGFA) were used to construct prognostic models. Patients were divided into high-risk and low-risk groups based on the calculated risk scores. Survival analysis showed that patients in the high-risk group had a significantly lower overall survival than those in the low-risk group (P < 0.05). Therefore, this prognostic model was an independent prognostic factor for predicting HNSC. In addition, patients in the low-risk group were more sensitive to multiple anti-cancer drugs. Functional correlation analysis showed a good correlation between the characteristic genes and HNSC metastasis, invasion, and angiogenesis. Conclusion This study established a new prognostic model for AAGs and may guide the selection of therapeutic agents for HNSC. These genes have important functions in the tumor microenvironment; it also provides a valuable resource for the future clinical trials investigating the relationship between HNSC and AAGs.

BACKGROUND:Platelet-derived growth factor A (PDGFA) has been shown to be upregulated in several tumors, contributing to their malignant phenotypes. However, its expression and function in head and neck squamous cell carcinoma (HNSC) are not clearly understood. Thus, we aimed to evaluate this issue using bioinformatic analyses and primary experimental validation. METHODS:The expression of PDGFA was analyzed using popular bio-databases and further validated by RT-PCR and immunohistochemical staining. Survival analyses were then performed. The association between PDGFA expression levels and immune cell infiltration in the immune microenvironment was assessed. RESULTS:PDGFA has been found to be significantly upregulated in a variety of cancers, including HNSC, and increased PDGFA expression may be an independent prognostic factor associated with immune cell infiltration in HNSC. CONCLUSION:Overexpression of PDGFA in HNSC is significantly associated with poor prognosis and immune cell infiltration in the tumor microenvironment (TME). PDGFA has potential as a molecular indicator for diagnosis, prognosis, and immune processes in HNSC.

Lymph node metastasis (LNM) is a significant prognostic factor in head and neck cancer (HNC) patients. To obtain a better understanding of the worldwide prevalence and current research status, the authors conducted a comprehensive bibliometric analysis of literature published from 2000 to 2022. The contributions of institutions, journals, countries or regions, cited literature, keywords, and authors in global publications were concisely summarized using the COOC and VosViewer software tools. The data were extracted from the expansive Web of Science database. A total of 5478 papers were collected for analysis, and the number of publications has exhibited exponential growth over the last 22 years. The United States emerged as the most productive country, closely followed by China. Noteworthy institutions for their high productivity include the Sloan-Kettering Cancer Center, Sun Yat-Sen University, and the University of Texas MD Anderson Cancer Center. The Head & Neck and Oral Oncology journals lead in terms of publication volume. The main areas of research in this field were prognostication, radiotherapy, survival rates, sentinel lymph node biopsy, and the human papillomavirus. In addition, the analysis of author collaboration networks yielded valuable insights into the collaborative relationships within this research domain. Our research has identified the primary characteristics of highly impactful studies on LNM in HNC, providing significant insights into the advancements made in this area of research.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck. Its pathogenesis is complicated and needs further investigation. The aim of this study was to investigate the expression and clinical significance of WWP1 in NPC. Bioinformatics approaches were used to evaluate the expression and functions of WWP1 in NPC. WWP1 protein expression was then detected by immunohistochemistry on a tissue microarray in an NPC cohort and its association with clinical features and prognosis was determined. In addition, WWP1 expression was knocked down in NPC cells using RNA interference, and their colony formation and invasion abilities were assessed. A total of 25 genes closely related to WWP1, which may be enriched in different pathways, were filtered out. WWP1 expression was significantly higher in NPC cells than in normal controls. High WWP1 expression was correlated with lymph node metastasis, tumor recurrence, clinical stage and poor prognosis. Knockdown of WWP1 resulted in attenuated proliferation and invasion of NPC cells. The results suggest that WWP1 may serve as a novel biomarker and prognostic factor for NPC and a potential therapeutic target worthy of further investigation.

BACKGROUNDBetel nut chewing is a significant risk factor for oral cancer due to arecoline, its primary active component. Resveratrol, a non-flavonoid polyphenol, possesses anti-cancer properties. It has been shown to inhibit arecoline-induced oral malignant cells in preliminary experiments but the underlying mechanism remains unclear. This research therefore aimed to explore the potential therapeutic targets of resveratrol in treating arecoline-induced oral cancer.METHODSData mining identified common targets and hub targets of resveratrol in arecoline-induced oral cancer. Gene set variation analysis (GSVA) was used to score and validate the expression and clinical significance of these hub targets in head and neck cancer (HNC) tissues. Molecular docking analysis was conducted on the hub targets. The effect of resveratrol intervention on hub targets was verified by experiments.RESULTSSixty-one common targets and 15 hub targets were identified. Hub targets were highly expressed in HNC and were associated with unfavorable prognoses. They played a role in HNC metastasis, epithelial-mesenchymal transition, and invasion. Their expression also affected immune cell infiltration and correlated negatively with sensitivity to chemotherapeutic agents such as bleomycin and docetaxel. Experiments demonstrated that resveratrol down-regulated the expression of the hub targets, inhibited their proliferation and invasion, and induced apoptosis.CONCLUSIONResveratrol inhibits the arecoline-induced malignant phenotype of oral epithelial cells by regulating the expression of some target genes, suggesting that resveratrol may be used not only as an adjuvant treatment for oral cancer, but also as an adjuvant for oral cancer prevention due to its low toxicity and high efficacy. (c) 2024 Society of Chemical Industry.

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.

Objectives: Nasopharyngeal carcinoma (NPC) is a highly aggressive, insidious, recurrent, and metastatic head-and-neck malignancy with a poor prognosis. Bromodomain-containing 4 (BRD4) was upregulated in various tumors and was associated with poor prognosis. Therefore, this study aimed to investigate the biological function of BRD4 in NPC and the molecular mechanisms of expression regulation. Materials and Methods: Based on biological big data, the expression, clinical significance, and possible biological functions of BRD4 in head-and-neck cancer were explored by bioinformatics. Then, based on a tissue microarray containing a cohort of NPC, BRD4 protein expression was detected by immunohistochemistry to explore its clinical significance and impact on prognosis. Statistical analysis: A p-value less than 0.05 was considered as significant. Results: BRD4 expression was upregulated in NPC and positively correlated with metastasis, higher tumor grades, and clinical stages, which might be positively correlated with copy number variation, CD4+ T cells, and immune checkpoint suppressor genes. Moreover, the sensitivity of cancer cells to paclitaxel and gemcitabine was negatively correlated with BRD4 expression. In addition, immunohistochemical staining showed that BRD4 was overexpressed in NPC tissues, which was correlated with lymph node metastasis and poor clinical outcomes. Conclusions: BRD4 is highly expressed in NPC tissues and is associated with a poor prognosis. Its aberrant expression may be closely linked to alterations in the immune microenvironment and chemotherapeutic resistance. Moreover, BRD4 is not only an oncogene in NPC but also a potential therapeutic target.

Objectives. Nicotine is an ingredient of tobacco, and exposure to nicotine increases the risks of various cancers, including oral cancer. Previous studies have focused on the addictive properties of nicotine, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process through which nicotine promotes the occurrence and development of oral cancer via data mining and experimental verification.Methods. This study involved three parts. First, key genes related to nicotine-related oral cancer were screened through data mining; second, the expression and clinical significance of a key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.Results. SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways, such as the tumor necrosis factor and apelin pathways, and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to bleomycin and docetaxel.Conclusion. This study revealed SERPINE1 as a key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.

BackgroundArecoline, the main component of betel nut, induces malignant transformation of oral cells through complicated unclear mechanisms. Thus, we aimed to screen the key genes involved in Arecoline-induced oral cancer and further verify their expressions and roles. MethodsThis study included a data-mining part, a bioinformatics verification part, and an experimental verification one. First, the key gene related to oral cancer induced by Arecoline was screened. Then, the expression and clinical significance of the key gene in head and neck/oral cancer tissues were verified, and its downstream mechanisms of action were explored. Afterwards, the expression and roles of the key gene were verified by experiments at the histological and cytological levels. ResultsMYO1B was identified as the key gene. Overexpression of MYO1B was associated with lymph node metastasis and unfavorable outcomes in oral cancer. MYO1B may be mainly related to metastasis, angiogenesis, hypoxia, and differentiation. A positive correlation between MYO1B and the infiltration of macrophages, B cells, and dendritic cells was presented. MYO1B might have a close relationship with SMAD3, which may be enriched in the Wnt signaling pathway. MYO1B suppression markedly inhibited the proliferation, invasion, and metastasis abilities of both Arecoline-transformed oral cells and oral cancer cells. ConclusionThis study revealed MYO1B as a key gene in Arecoline-induced oral tumorigenesis. MYO1B might be a novel prognostic indicator and therapeutic target for oral cancer.

1 病例资料 患儿,男,1岁2月,因"发现左外耳道新生物3月"于2017年7月12日入院,3月前患儿家属发现患儿左外耳道一粉红色新生物,无耳流脓、流血等症状.1月前患儿家属感新生物稍增大,故就诊我科.查体:左外耳道口见一粉红色肉芽状新生物,质韧,表面无红肿、破溃,不能推动,皮温不高,鼓膜完整,标志清.考虑患儿年龄较小,于2017年7月13日局麻下行左外耳道新生物切除术,术中距左耳道口0.5cm处见耳道后壁一粉红色肉芽状新生物,大小约0.4cm×0.4cm,完整切除肿物后局部压迫止血,术腔填塞碘仿纱条1条.

Cisplatin (DDP) resistance is a bottleneck in the treatment of head and neck cancer (HNC), leading to poor prognosis. Fisetin, a dietary flavonoid, has low toxicity and high antitumor activity with unclear mechanisms. We intended to predict the targets of fisetin for reversing DDP-resistance and further verify their expressions and roles. A network pharmacology approach was applied to explore the target genes. The hub genes were screened out and subjected to molecular docking and experimental verification (in vivo and in vitro). Thirty-two genes common to fisetin and DDP-resistance were screened, including three hub genes, namely HSP90AA1, PPIA, and PTPRS. Molecular docking suggested that fisetin and the candidate proteins could bind tightly. HSP90AA1 was identified as the key gene. Administration of fisetin increased the sensitivity of chemoresistant cells (Cal27/DDP and FaDu/DDP) to DDP, accompanied by the downregulation of HSP90AA1 and IL-17. HSP90AA1 silencing increases the sensitivity of DDP-resistant cells to DDP, which was mediated by IL-17. In summary, fisetin might inhibit the chemoresistance of HNC cells to DDP by targeting the HSP90AA1/IL-17 pathway. Several hub genes might be the targets of fisetin for reversing DDP-resistance in HNC cells and might also serve as prognostic factors and therapeutic targets for HNC.

Recurrence and metastasis of nasopharyngeal carcinoma (NPC) after radical treatment is a major bottleneck in clinical treatment. Therefore, we aimed to find the genes related to metastasis after radical treatment in NPC patients. Public datasets in the Gene Expression Omnibus database were consulted and the differential expression genes (DEGs) were screened out. The possible roles of the DEGs were annotated by Gene Ontology, and pathway analysis. The hub genes/proteins were then filtered out through protein-protein interaction network construction. The key genes were sifted out from the hub genes, and their expressions were verified by qPCR and immunohistochemistry assays. A total of 28 DEGs were filtered out, which may be enriched in different signaling pathways. Of these DEGs, 11 hub genes were filtered out, among which EPHB2 was shown to be over-expressed in NPC tissues. Further experimental assays confirmed that EPHB2 was overexpressed in NPC cells, which might be associated with tumor recurrence, neck lymph node metastasis, and advanced clinical stages. Moreover, high EPHB2 expression predicted poor prognosis in NPC patients. EPHB2 might be a novel recurrence-related biomarker and a prognostic factor for NPC. Moreover, it might also be used as a potential treatment target for NPC.