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Head and neck cancers are a growing global health concern, with oral squamous cell carcinoma (OSCC) accounting for 90­95% of all cases within this region. OSCC near dental implants can resemble benign inflammatory lesions, posing diagnosis challenging. A 74-year-old man presented with an ulcerated, asymptomatic lesion in the upper right alveolar mucosa, initially misdiagnosed as a benign inflammatory condition due to its proximity to a dental implant. Afterwards the lesion was identified as OSCC, and the patient underwent surgical treatment. Three years post-surgery, a white plaque appeared near the grafted area and was diagnosed as oral leukoplakia. Although, over the course of fourteen years, the patient had no recurrences or metastases. Therefore, clinicians should be aware that while most lesions around dental implants are of inflammatory origin, OSCC must be considered in differential diagnosis in cases that do not respond to standard treatments. (AU)

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This case report highlights the delay in the diagnosis of oral squamous cell carcinoma (OSCC) and the inappropriate use of low-level laser therapy (LLLT) in dentistry. OSCC is a malignant neoplasm that affects the oral cavity and can have severe consequences if not diagnosed and treated appropriately and promptly. The patient presented with a persistent oral lesion that was initially diagnosed as a traumatic injury and treated with LLLT, which led to a delay in the correct diagnosis of OSCC. The case emphasizes the importance of early detection and proper management of oral lesions to prevent the progression of malignant conditions. It also emphasizes the need for professional knowledge regarding the applicability of LLLT in dental practice. Dental professionals should be vigilant in recognizing suspicious oral lesions and promptly refer patients for further evaluation and appropriate treatment to ensure optimal outcomes.

Este informe de un caso destaca el retraso en el diagnóstico del carcinoma espinocelular oral (CEC) y el uso inapropiado de la terapia con láser de baja potencia (LBP) en odontología. El CEC es una neoplasia maligna que afecta la cavidad oral y puede tener graves consecuencias si no se diagnostica y trata de manera adecuada y oportuna. La paciente presentó una lesión oral persistente que inicialmente se diagnosticó como lesión traumática y se trató con LBP, lo que llevó a un retraso en el diagnóstico correcto del CEC. El caso enfatiza la importancia de la detección temprana y el manejo adecuado de las lesiones orales para prevenir la progresión de condiciones malignas. También resalta los riesgos asociados con el uso inapropiado de la LBP en la práctica odontológica. Los profesionales de la odontología deben estar atentos a las lesiones orales sospechosas y remitir a los pacientes de manera oportuna para una evaluación adicional y un tratamiento adecuado, con el fin de garantizar mejores resultados.

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Introducción: El cáncer de cabeza y cuello (CaCyC) representa una alta carga de enfermedad. El retraso del inicio de tratamiento es un factor predictor independiente de mortalidad. Objetivo: Describir los tiempos entre hitos claves diagnósticos y terapéuticos de pacientes con CaCyC atendidos en Hospital Sótero del Río (CASR) y comparar la experiencia local con guías internacionales. Material y Método: Estudio descriptivo-retrospectivo de pacientes presentados en Comité Oncológico de cabeza y cuello (COCYC) del CASR desde septiembre 2020 hasta julio 2022. Se analizan los tiempos críticos del proceso diagnóstico y terapéutico. Resultados: 78 pacientes se seleccionan, 75,5% con carcinoma escamoso. La mediana de tiempos entre derivación desde atención primaria (APS) y evaluación CASR es 2 días, entre evaluación y biopsia es 9 días, y entre diagnóstico histológico e inicio de tratamiento en cualquier modalidad de 27 días. Se comparan los tiempos críticos según los plazos definidos por el Cancer Council Australia. Las tasas de cumplimiento entre derivación APS y evaluación CASR es 67%. Según el tratamiento recibido, la tasa de cumplimiento desde el ingreso al inicio de tratamiento es 70% para cirugía exclusiva, 0% para inicio de radioterapia, y 20% para radioquimioterapia. Para cirugía y radioterapia adyuvante, la tasa es 67% entre evaluación y cirugía, y 6% entre cirugía y radioterapia. Conclusión: Se describen los tiempos entre hitos claves diagnósticos y terapéuticos. Los tiempos de derivación desde APS e inicio de terapias quirúrgicas son comparables a la literatura internacional, pero los tiempos en inicio de radioterapia son mejorables.

Introduction: Head and neck cancer (H&NCa) represents a high burden of disease. Delay in starting treatment is an independent predictor of mortality. Objective: To describe the times between the key diagnostic and therapeutic milestones of patients with H&NCa treated at the Hospital Sótero del Río (CASR) and compare the local experience with international guidelines. Material and Method: descriptive-retrospective study of patients presented to the Head and Neck Oncology Committee (H&NOCO) of the CASR from September 2020 to July 2022. The critical times of the diagnostic and therapeutic process are analyzed. Results: 78 patients are selected, 75.5% with squamous cell carcinoma. The median time between referral from primary care (PC) and CASR evaluation is 2 days, between evaluation and biopsy is 9 days, and between histological diagnosis and initiation of treatment in any modality is 27 days. Critical times are compared according to the deadlines defined by Cancer Council Australia. Compliance rates between PC referral and CASR admission is 67%. Depending on the treatment received, the compliance rate from admission to the start of treatment is 70% for exclusive surgery, 0% for the start of radiotherapy, and 20% for radiochemotherapy. For surgery and adjuvant radiotherapy, the rate is 67% between evaluation and surgery, and 6% between surgery and radiotherapy. Conclusion: Waiting times between key diagnostic and therapeutic process are described. The times of referral from PC and start of surgical therapies are comparable to the international literature. However, times regarding the start radiotherapy can be improved.

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OBJECTIVE@#To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC).@*METHODS@#Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected.@*RESULTS@#Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production.@*CONCLUSIONS@#This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.

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Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac4C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac4C modification sites, thereby providing a potent sequencing tool for tRNA-ac4C research. Our findings expand the repertoire of tRNA ac4C modifications and identify a role of tRNA ac4C in the regulation of mRNA translation in HNSCC.

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Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

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Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

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Context and objective. Human papillomavirus (HPV) is one of the factors involved in the occurrence of head and neck squamous cell carcinoma (HNSCC). This is also considered a predictive factor for the survival of HNSCC, especially in oropharynx. The objective was to identify predictors of HNSCC-related mortality and assess the impact of HPV status on the survival of patients with HNSCC. Methods. A historical cohort study was conducted in two reference hospitals in Kinshasa between 2012 and 2023. Kaplan Meier curves were constructed to describe survival (time to death) and were evaluated using the Log-Rank test. Predictors of mortality were tested by Cox proportional hazard. Results. 95 patients (mean age 52.5 ± 15.0 years, male, 64.2%) were included. HPV-positive patients had better overall survival than HPV-negative patients (440 vs 245 days; p ≤0.001). Oropharyngeal location [HR 0.523; 95% CI 0.337 ­ 0.813; p=0.004] and the expression of Protein 16 (p16) [HR 0.365; 95% CI 0.221 ­ 0.604; p<0.001] were the predictors of mortality in bivariate analysis. After adjusting the parameters, only the expression of p16 [HR 0.334; 0.185 ­ 0.605; p<0.001] significantly reduced patient mortality (p<0.001). Conclusion. Positive HPV status has a significant and favorable impact on the overall survival of HNSCC patients.

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Introdução: o carcinoma de células escamosas (CCE) é uma neoplasia maligna que pode afetar as estruturas sinonasais e se estender para a cavidade oral. Objetivo: relatar o processo de diagnóstico de um CCE sinonasal, o qual cursou com envolvimento oral. Relato do caso: um homem de 61 anos procurou atendimento odontológico com um aumento de volume doloroso em palato duro, rebordo alveolar anterior superior e dorso nasal esquerdo, com a evolução de aproximadamente 2 meses. Sua queixa inicial era congestão nasal. A tomografia computadorizada demonstrou uma lesão ampla e extensa com destruição de cortical vestibular e palatina, além de envolvimento sinonasal. Com a hipótese diagnóstica de neoplasia sinonasal, uma biópsia incisional foi realizada. Resultado: microscopicamente, observou-se células epiteliais neoplásicas que se organizavam em ninhos e cordões invadindo o tecido conjuntivo adjacente que apresentavam individualmente pleomorfismo nuclear e celular, nucléolo evidentes e hipercromasia nuclear. Áreas de necrose central também eram notadas. Com base nas características clínicas, imagenológicas e histopatológicas, o diagnóstico final foi de CCE sinonasal não queratinizante. O tumor foi estadiado pela equipe médica como T3N0M0 (T3 = tamanho do tumor > 2cm com invasão de ossos faciais, sem evidência de metástase nodal N=0 ou à distância M=0). O paciente foi tratado com quimioterapia (Cisplatina e Gencitabina) e 70Gy de radioterapia de indução como terapia inicial e posterior ressecção cirúrgica. Conclusão: a avaliação clínica, imagenológica e exame histopatológico permitiram o diagnóstico eficaz do CCE sinonasal não queratinizante.

Introduction: squamous cell carcinoma (SCC) is a malignant neoplasm that can affect the sinonasal structures and extend to the oral cavity. Objective: to report the process of diagnosis and management of a sinonasal SCC, which had oral involvement. Case report: a 61-year-old man sought dental care with a painful swelling in the hard palate, anterior superior alveolar ridge and left nasal dorsum for a period of approximately 2 months. His initial complaint was nasal congestion. Computed tomography showed a wide and extensive lesion with destruction of the buccal and palatal cortex, in addition to sinonasal involvement. With the diagnostic hypothesis of sinonasal neoplasia, an incisional biopsy was performed. Results: microscopically, neoplastic epithelial cells grouped in nests and cords invading the adjacent connective tissue were observed; individually they presented nuclear and cellular pleomorphism, evident nucleolus and nuclear hyperchromasia. Areas of central necrosis were also noted. Based on the clinical, imaging and histopathological characteristics, the final diagnosis was non- keratinizing sinonasal SCC. The tumor was staged by the medical team as T3N0M0 (T3 = tumor size > 2cm with invasion of facial bones, without evidence of nodal metastasis N=0 or distant metastasis M=0), and the patient was treated with chemotherapy (Cisplatin and Gemcitabine) and 70Gy of induction radiotherapy as initial therapy and subsequent surgical resection. Conclusion: clinical, imaging and histopathological evaluation allowed an effective diagnosis of non- keratinizing sinonasal SCC.

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Introdução: O câncer bucal é apontado como um problema de saúde relevante e apresenta alta taxa de incidência e mortalidade. O consumo de tabaco e álcool são considerados os principais fatores de risco para sua ocorrência. Apesar dos avanços relacionados a detecção, diagnóstico e tratamento, grande parte dos pacientes ainda é diagnosticada com a doença em estágio avançado. Objetivo: Estabelecer os principais fatores associados ao atraso no diagnóstico do câncer bucal. Material e Métodos: Foram pesquisados artigos nas bases de dados MEDLINE/PubMed, SciELO e Lilacs, com os descritores: delayed oral cancer; delayed diagnosis oral cancer; oral cancer young patients; e HPV oral cancer patients. Como critérios de inclusão, foram delimitados artigos completos e disponíveis integramente. Publicações não relacionadas a delimitação do tema e ao objetivo do estudo foram excluídas. Resultados: Foram encontrados 513 artigos, dos quais 118 foram lidos na íntegra e 96 por fim selecionados, conforme critérios de inclusão e exclusão. Os dados indicaram que o atraso no diagnóstico do câncer bucal é frequente e relacionado ao atraso pelo paciente, atraso pelo profissional de saúde e atraso no tratamento, com destaque ao atraso pelo paciente. Conclusão: O diagnóstico precoce é o meio mais eficaz de reduzir as taxas de mortalidade e melhorar o prognóstico e qualidade de vida de pacientes com câncer bucal. Dessa forma, estratégias que objetivam a redução de diagnósticos realizados tardiamente devem ser consideradas.

Introduction: Oral cancer is identified as a relevant health problem and has a high incidence and mortality rate. Tobacco and alcohol consumption are considered the main risk factors for its occurrence. Despite advances related to detection, diagnosis and treatment, a large proportion of patients are still diagnosed with the disease at an advanced stage. Objective: To establish the main factors associated with delays in the diagnosis of oral cancer. Material and Methods: Articles were searched in the MEDLINE/PubMed, SciELO and Lilacs databases, with the descriptors: delayed oral cancer; delayed diagnosis of oral cancer; oral cancer young patients; and oral HPV cancer patients. As inclusion criteria, complete and fully available articles were delimited. Publications not related to the delimitation of the topic and the objective of the study were excluded. Results: 513 articles were found, of which 118 were read in full and 96 were finally selected, according to inclusion and exclusion criteria. The data indicated that delays in diagnosing oral cancer are frequent and related to delays by the patient, delays by healthcare professionals and delays in treatment, with emphasis on delays by the patient. Conclusion: Early diagnosis is the most effective way to reduce mortality rates and improve the prognosis and quality of life of patients with oral cancer. Therefore, strategies that aim to reduce late diagnoses should be considered.

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OBJECTIVES@#Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC.@*METHODS@#We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients.@*RESULTS@#The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r＝0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P＝0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low.@*CONCLUSIONS@#Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.

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Objective: To investigate the relationship between the long-non-coding RNA LINC00342 expression and the clinicopathological parameters of head and neck squamous cell carcinoma (HNSCC) and the biological function of LINC00342 in HNSCC cells. Methods: The expression level of LINC00342 in the HNSCC was analyzed using transcriptome sequencing data from TCGA (The Cancer Genome Atlas) database, and the expressions of LINC00342 in laryngeal squamous cell carcinoma tissues (LSCC) of 27 patients in the First Hospital of Shanxi Medical University were detected by transcriptome sequencing. The expression levels of LINC00342 in human embryonic lung diploid cells 2BS, HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 were determined by real-time quantitative polymerase chain reaction (qPCR). RNAi (RNA interference) was used for LINC00342 knockdown in HNSCC cell lines, and the changes of malignant phenotype in the tumor cells after LINC00342 knockdown were examined by cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell invasion and migration assays. Bioinformatics analysis was performed to construct a LINC00342-centered competing endogenous RNA (ceRNA) regulatory network, and GO (Gene Ontology) enrichment analysis was performed. Statistical analysis and graphing were performed using SPSS 25.0 software and GraphPad Prism 6 software. Results: Mean LINC00342 levels in HNSCC tissues and TCGA database were higher than that in normal control tissues, but with no significantly statistical difference (P=0.522). LINC00342 expression levels were positively correlated with cervical lymph node metastasis and pathological grade in patients with HNSCC, with higher expression in male patients than in female patients (P<0.05). Transcriptome sequencing analysis showed that mean expression level of LINC00342 in LSCC tissues of 27 patients was significantly higher than that in the paired adjacent normal mucosa tissues (t=1.56, P=0.036). LINC00342 expression was significantly upregulated in HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 (t-values of -12.17, -23.26 and -388.57, respectively; all P<0.001). Knockdown of LINC00342 by transfecting si-LINC00342-1 and si-LINC00342-2 inhibited HNSCC cell proliferation (t-values of 8.95 and 4.84, 2.70 and 5.55, 2.02 and 3.70, respectively), colony formation (t-values of 6.66 and 6.17, 7.38 and 11.65, 4.90 and 5.79, respectively), migration (t-values of 8.21 and 7.19, 5.76 and 6.46, 6.28 and 9.92, respectively) and invasion abilities (t-values of 9.29 and 10.25, 11.30 and 11.36, 8.02 and 8.66, respectively), but promoting apoptosis in cell lines FD-LSC-1 and CAL-27 (t-values of -2.21 and -5.83, -3.05 and -5.25 respectively) (all P-values<0.05). The LINC00342-centered ceRNA network consists of 10 downregulated microRNA and 647 upregulated mRNA nodes. GO analysis results indicated that LINC00342-regulated mRNAs were enriched in 22 biological processes, 32 molecular functions, and 12 cellular components. Conclusion: High level of LINC00342 is associated with the malignant progression of HNSCC. LINC00342 promotes the proliferation, migration, invasion, and antagonizes apoptosis of HNSCC cells, which serves as a potential molecular marker in HNSCC.

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Tongue squamous cell carcinoma is highly malignant and has a poor prognosis. In this study, we aimed to combine whole-genome sequencing, whole-genome methylation, and whole-transcriptome analyses to understand the molecular mechanisms of tongue squamous cell carcinoma better. Oral tongue squamous cell carcinoma and adjacent normal tissues from five patients with tongue squamous cell carcinoma were included as five paired samples. After multi-omics sequencing, differentially methylated intervals, methylated loop sites, methylated promoters, and transcripts were screened for variation in all paired samples. Correlations were analyzed to determine biological processes in tongue squamous cell carcinoma. We found five mutated methylation promoters that were significantly associated with mRNA and lncRNA expression levels. Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade, which is associated with cancer progression and the development of drug resistance during treatment. The prognostic signature models constructed based on WDR81 and HNRNPH1 and combined clinical phenotype-gene prognostic signature models showed high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings. We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs. Collectively, changes in transcript levels affect the prognosis of tongue squamous cell carcinoma patients.

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Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.

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Tumor-associated macrophages (TAMs) play crucial roles in tumor progression and immune responses. However, mechanisms of driving TAMs to antitumor function remain unknown. Here, transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12 (RGS12) regulates pathologic processes and immune-related pathways. Mice with RGS12 knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues, and extensive proliferation and invasion of oral cancer cells. RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length. Mechanistically, RGS12 associates with and activates MYC binding protein 2 (MYCBP2) to degrade the cilia protein kinesin family member 2A (KIF2A) in TAMs. Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.

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Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).

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Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.

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Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC.

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Cancer stem cell-like cells (CSCs) play an integral role in the heterogeneity, metastasis, and treatment resistance of head and neck squamous cell carcinoma (HNSCC) due to their high tumor initiation capacity and plasticity. Here, we identified a candidate gene named LIMP-2 as a novel therapeutic target regulating HNSCC progression and CSC properties. The high expression of LIMP-2 in HNSCC patients suggested a poor prognosis and potential immunotherapy resistance. Functionally, LIMP-2 can facilitate autolysosome formation to promote autophagic flux. LIMP-2 knockdown inhibits autophagic flux and reduces the tumorigenic ability of HNSCC. Further mechanistic studies suggest that enhanced autophagy helps HNSCC maintain stemness and promotes degradation of GSK3β, which in turn facilitates nuclear translocation of β-catenin and transcription of downstream target genes. In conclusion, this study reveals LIMP-2 as a novel prospective therapeutic target for HNSCC and provides evidence for a link between autophagy, CSC, and immunotherapy resistance.

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Microorganisms are one of the important factors which maintain the homeostasis of human health. Despite recent advances, the relationship between microorganisms and head and neck squamous cell carcinoma （HNSCC） is still unclear, and the impact of microorganisms on the incidence and prognosis of HNSCC cannot be neglected. Therefore, this article provides a systematic and comprehensive review summarizing the epidemiological evidence of microbial dysbiosis related to HNSCC and discusses the associations between them.