RESUMO
Significance: Oral cancer surgery requires accurate margin delineation to balance complete resection with post-operative functionality. Current in vivo fluorescence imaging systems provide two-dimensional margin assessment yet fail to quantify tumor depth prior to resection. Harnessing structured light in combination with deep learning (DL) may provide near real-time three-dimensional margin detection. Aim: A DL-enabled fluorescence spatial frequency domain imaging (SFDI) system trained with in silico tumor models was developed to quantify the depth of oral tumors. Approach: A convolutional neural network was designed to produce tumor depth and concentration maps from SFDI images. Three in silico representations of oral cancer lesions were developed to train the DL architecture: cylinders, spherical harmonics, and composite spherical harmonics (CSHs). Each model was validated with in silico SFDI images of patient-derived tongue tumors, and the CSH model was further validated with optical phantoms. Results: The performance of the CSH model was superior when presented with patient-derived tumors ( P -value < 0.05 ). The CSH model could predict depth and concentration within 0.4 mm and 0.4 µ g / mL , respectively, for in silico tumors with depths less than 10 mm. Conclusions: A DL-enabled SFDI system trained with in silico CSH demonstrates promise in defining the deep margins of oral tumors.
Assuntos
Simulação por Computador , Aprendizado Profundo , Neoplasias Bucais , Imagem Óptica , Imagens de Fantasmas , Cirurgia Assistida por Computador , Imagem Óptica/métodos , Humanos , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Cirurgia Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Margens de ExcisãoRESUMO
BACKGROUND: Locally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant clinical challenge despite being partially responsive to standard treatment modalities. This study investigates the prognostic implications of programmed death-ligand 1 (PD-L1) expression in these tumors, focusing on its association with treatment outcomes and the immune microenvironment. METHODS: We assessed tumor-infiltrating lymphocytes (TILs) in 132 patients with OCSCC to evaluate their impact on survival. Multiplex immunohistochemistry staining for CD3, CD68, CD11c, PD-L1, and P40 was used to explore correlations with clinical outcomes in patients with early-stage (n=22) and locally advanced (n=36) OCSCC. These initial findings were validated through differential gene expression analysis, gene set enrichment, and immune cell deconvolution in a The Cancer Genome Atlas cohort of 163 locally advanced OCSCC tumors. Additionally, single-cell RNA sequencing (scRNA-seq) on a smaller cohort (n=10) further characterized the PD-L1hi or PD-L1lo cancer cells in these tumors. RESULTS: Elevated PD-L1 expression was associated with poor outcomes in patients with locally advanced OCSCC undergoing standard adjuvant therapy, irrespective of "hot" or "cold" classification based on TILs assessment. PD-L1hi tumors exhibited an active immune response phenotype, enriched with M1 macrophages, CD8+ T cells and T regulatory cells in the tumor microenvironment. Notably, the negative impact of PD-L1 expression on outcomes was primarily attributed to its expression by cancer cells, rather than immune cells. Furthermore, scRNA-seq revealed that immune interactions were not essential for PD-L1 upregulation in cancer cells, instead, complex regulatory networks were involved. Additionally, PD-L1lo locally advanced tumors exhibited more complex pathway enrichment and diverse T-cell populations compared with those in the early-stage. CONCLUSION: Our findings underscore the prognostic significance of PD-L1 expression in locally advanced OCSCC, and unveil the complex interplay between PD-L1 expression, immune responses, and molecular pathways in the tumor microenvironment. This study provides insights that may inform future therapeutic strategies, including the possibility of tailored immunotherapeutic approaches for patients with PD-L1hi locally advanced OCSCC.
Assuntos
Antígeno B7-H1 , Linfócitos do Interstício Tumoral , Neoplasias Bucais , Microambiente Tumoral , Humanos , Antígeno B7-H1/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/imunologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Masculino , Feminino , Pessoa de Meia-Idade , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Idoso , Prognóstico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Adulto , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidadeRESUMO
BACKGROUND: Orofacial neoplasms in children and young adults may differ significantly from those observed in adults. Our aim was to describe the epidemiological characteristics of histologically diagnosed orofacial neoplasms among children and young adults in Nigeria. METHODS: This was a multicenter cross-sectional study across geopolitical zones in Nigeria. Annual reports of clinical information and surgical biopsies submitted at the Oral Pathology Laboratory, clinic day registries, surgical day case registries and operative theatre registries were retrieved from January 2008 to March 2024. The relevant demographic data were obtained for each patient. The study subjects were categorized by age into children, adolescents and young adults. Tissue involvement was classified as soft tissue involvement, bony involvement or both soft tissue and bony involvement. The site and behaviour of the lesions were subdivided according to the ICD-10 codes. Statistical analysis was performed via the R programming language. RESULTS: A total of 1889 cases were observed during the period under review, with a mean age of 15 years. Cases were more common in females (52%) and in young adults (47%). Most cases were benign neoplasms (85%), and bony affectation (54%) was slightly predominant. Odontogenic tumours (38%) and fibro-osseous lesions (20%) were the most common category of lesions observed, whereas salivary gland tumours (2.2%) and neoplasms of epithelial origin (2.5%) were the least common. Neoplasms in children involved mostly soft tissues, whereas those in adolescents and young adults had a preference for bone (p < 0.001). In all age groups, benign lesions were mostly observed in the mouth and pharynx. For malignant lesions, in children, the bones of the skull and face were mostly involved, whereas in adolescents, the mandible was the predominant site (p < 0.001). In children, mesenchymal neoplasms were the most prevalent category of lesions, whereas in both adolescents and young adults, odontogenic tumours were more common. The proportion of malignant neoplasms in males was significantly greater than that in females (p < 0.001). CONCLUSION: This study revealed that although most biopsied orofacial lesions were more often benign, the proportion of malignant neoplasms in this population was greater than that previously reported.
Assuntos
Neoplasias Bucais , Humanos , Nigéria/epidemiologia , Adolescente , Feminino , Criança , Masculino , Estudos Transversais , Adulto Jovem , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/patologia , Pré-Escolar , AdultoRESUMO
Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms that regulate metabolism, immune function, and health. There are three types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokines, including interleukins, interferons, and tumor necrosis factor. Second, bacteria can interact directly with host cells by secreting toxins or by binding to membrane receptors. Finally, the production of metabolites by bacteria may also contribute to carcinogenesis. The importance of the bacteria level and composition in the transition of oral precancerous lesions to cancer has been demonstrated. The relationships of changes in microbiome composition with smoking, inflammation in healthy individuals, as well as with the development of oral cancer in patients, have been studied.
Assuntos
Microbiota , Neoplasias Bucais , Boca , Humanos , Neoplasias Bucais/microbiologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Boca/microbiologia , Citocinas/metabolismo , Fumar/efeitos adversos , Inflamação/microbiologia , Carcinogênese , Bactérias/metabolismo , Bactérias/genética , Bactérias/patogenicidade , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/genéticaRESUMO
Histopathologically, oral squamous cell carcinoma (OSCC) consists of well-defined interfaces with adjacent non-cancerous epithelium. Previously, we found that SCC tissues expressed higher levels of specific proteins at this interface. Ladinin-1 (LAD1) is one of the specific molecules that has increased expressions in cancer fronts; however, its function in OSCC is unknown. Therefore, this study aimed to elucidate the function of LAD1 in human OSCC cells. LAD1 was localized on the actin arc at the distal periphery of cell clusters in the OSCC cell lines HSC-2, HSC-3, and HSC-4. When LAD1 was knocked down, cellular migration was repressed in wound scratch assays but was reversed in three-dimensional collagen gel invasion assays. Characteristic LAD1 localization along actin arcs forming the leading edge of migrating cells was diminished with loss of filopodia formation and ruffling in knockdown cells, in which the expression levels of cell motility-related genes-p21-activated kinase 1 (PAK1) and caveolin-1 (CAV1)-were upregulated and downregulated, respectively. LAD1 expression was also associated with the downregulation of vimentin and increased histological differentiation of OSCC. These results suggest that LAD1 is involved in actin dynamics during filopodia and lamellipodia formation, and in maintaining the epithelial phenotype of OSCC cells.
Assuntos
Actinas , Carcinoma de Células Escamosas , Movimento Celular , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Actinas/metabolismo , Quinases Ativadas por p21/metabolismo , Quinases Ativadas por p21/genética , Vimentina/metabolismo , Vimentina/genética , Caveolina 1/metabolismo , Caveolina 1/genética , Regulação Neoplásica da Expressão Gênica , Fenótipo , Células Epiteliais/metabolismo , Células Epiteliais/patologiaRESUMO
BACKGROUND: A variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis. METHODS: Data on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed. RESULTS: Hypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage. CONCLUSIONS: Preoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker.
Assuntos
Carcinoma de Células Escamosas , Metástase Linfática , Neoplasias Bucais , Estadiamento de Neoplasias , Tromboelastografia , Humanos , Tromboelastografia/métodos , Masculino , Feminino , Neoplasias Bucais/patologia , Neoplasias Bucais/sangue , Neoplasias Bucais/cirurgia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Prognóstico , Período Pré-OperatórioRESUMO
BACKGROUND: The Surgical Tool for Auditing Records scoring system [STAR] focuses on surgical record auditing with promising outcomes. It offers a structured approach to evaluating the quality of surgical notes. AIMS AND OBJECTIVES: This study aimed to assess the effectiveness of the STAR in evaluating oral surgical records and identifying areas for improvement in documentation practices. MATERIALS AND METHODS: The data was obtained from the Dental Information Archival Software (DIAS) of our institution. The sample size was determined using G*Power 3.1.9.4 software. Fifty consecutive oral surgery clinical records of oral squamous cell carcinoma patients were evaluated using STAR. Each record was reviewed for adherence to documentation standards including Initial Assessment (10 points), Follow-up Entries (8 points), Consent Documentation (7 points), Anesthesia Report (7 points), Surgical Log (9 points), and Discharge Synopsis (9 points). compiling a total STAR score (50 points). The data was tabulated in Google Sheets. The descriptive statistics with inter-observer agreement and the mean score were recorded. RESULTS: We observed that each of the 50 records received a score of 49/50 points on the STAR. Deductions were necessary in the Operative record section due to the lack of information regarding the sutures used. CONCLUSION: To summarize, this study emphasizes the effectiveness of the STAR scoring system in evaluating the quality of oral surgical records. Identifying deficiencies, particularly in documenting operative details, can improve the completeness and accuracy of patient records. It can ultimately enhance patient care and facilitate better communication among healthcare professionals.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Documentação/normas , Procedimentos Cirúrgicos Bucais/normas , Registros Odontológicos/normasRESUMO
Rationale: Immunosuppressive tumor microenvironment (iTME) plays an important role in carcinogenesis, and some macrophage subsets are associated with iTME generation. However, the sub-population characterization of macrophages in oral carcinogenesis remains largely unclear. Here, we investigated the immunosuppressive status with focus on function of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in oral carcinogenesis. Methods: We built a single cell transcriptome atlas from 3 patients simultaneously containing oral squamous cell carcinoma (OSCC), precancerous oral leukoplakia (preca-OLK) and paracancerous tissue (PCA). Through single-cell RNA sequencing and further validation using multicolor immunofluorescence staining and the in vitro/in vivo experiments, the immunosuppressive cell profiles were built and the role of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in the malignant transformation of oral leukoplakia was evaluated. Results: The iTME formed at preca-OLK stage, as evidenced by increased exhausted T cells, Tregs and some special subsets of macrophages and fibroblasts. Macro-IDO1 was predominantly enriched in preca-OLK and OSCC, distributed near exhausted T cells and possessed tumor associated macrophage transformation potentials. Functional analysis revealed the established immunosuppressive role of Macro-IDO1 in preca-OLK and OSCC: enriching the immunosuppression related genes; having an established level of immune checkpoint score; exerting strong immunosuppressive interaction with T cells; positively correlating with the CD8-exhausted. The immunosuppression related gene expression of macrophages also increased in preca-OLK/OSCC compared to PCA. The use of the IDO1 inhibitor reduced 4NQO induced oral carcinogenesis in mice. Mechanistically, IFN-γ-JAK-STAT pathway was associated with IDO1 upregulation in OLK and OSCC. Conclusions: These results highlight that Macro-IDO1-enriched in preca-OLK possesses a strong immunosuppressive role and contributes to oral carcinogenesis, providing a potential target for preventing precancerous legions from transformation into OSCC.
Assuntos
Transformação Celular Neoplásica , Indolamina-Pirrol 2,3,-Dioxigenase , Leucoplasia Oral , Macrófagos , Neoplasias Bucais , Análise de Célula Única , Microambiente Tumoral , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Leucoplasia Oral/imunologia , Leucoplasia Oral/genética , Leucoplasia Oral/patologia , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Camundongos , Microambiente Tumoral/imunologia , Transformação Celular Neoplásica/genética , Neoplasias Bucais/imunologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Análise de Célula Única/métodos , Análise de Sequência de RNA , Masculino , Tolerância Imunológica , Feminino , Carcinogênese/imunologia , Carcinogênese/genéticaRESUMO
Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.
Assuntos
Cromatina , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Humanos , Cromatina/genética , Cromatina/metabolismo , Histonas/metabolismo , Histonas/genética , Redes Reguladoras de Genes , Variações do Número de Cópias de DNARESUMO
Background: The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy. However, the identity of metastasis-initiating cells in human OSCC remains elusive, and whether metastases are hierarchically organized is unknown. Therefore, this study was conducted to understand the cellular origins and gene expression signature of OSCC at the single-cell level. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze cells from tissue of para-carcinoma (PCA: adjacent normal tissue not less than 2 cm from the tumour), carcinoma (CA), lymph node metastasis (LNM) from patients with OSCC and PCA and CA tissue from patients with second primary OSCC (SPOSCC) after radiotherapy of nasopharyngeal carcinoma (NPC). The cell types and their underlying functions were classified. The comparisons were then conducted between the homology and heterogeneity from cell types and both conservative and heterogeneous aspects of evolution were identified. Immunohistochemistry was performed to verify the makers of cell clusters and the expression level of novel genes. Results: A single-cell transcriptomic map of OSCC was created, including 16 clusters of PCA cells, 17 clusters of CA cells, 14 clusters of left LNM cells, and 14 clusters of right LNM cells. We also discovered two novel types of cells including CD1C-CD141-dendritic cells and CD1C+_B dendritic cells. Most of the non-cancer cells are immune cells, with two distinct clusters of T lymphocytes, B lymphocytes, CD1C-CD141-dendritic cells+ and CD1C+_B dendritic cells. We also classified cells into 15 clusters for SPOSCC after radiotherapy of NPC. Determining the upregulated expression levels of IL1RN and C15orf48 as novel markers using immunohistochemistry facilitated the correct classification of OSCC including SPOSCC after radiotherapy of NPC and the prediction of their prognosis. Conclusions: The findings provided an unprecedented and valuable view of the functional states and heterogeneity of cell populations in LNM of OSCC and SPOSCC after radiotherapy of NPC at single-cell genomic resolution. Moreover, this transcriptomic map discovered new cell types in mouth, and novel tumour cell-specific markers/oncogene.
Assuntos
Perfilação da Expressão Gênica , Neoplasias Bucais , Análise de Célula Única , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Metástase Linfática/patologia , Metástase Linfática/genética , Regulação Neoplásica da Expressão Gênica , Transcriptoma , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Microambiente Tumoral/imunologia , Masculino , Feminino , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologiaRESUMO
BACKGROUND: This study aims to evaluate the integration of optical coherence tomography (OCT) and peripheral blood immune indicators for predicting oral cancer prognosis by artificial intelligence. METHODS: In this study, we examined patients undergoing radical oral cancer resection and explored inherent relationships among clinical data, OCT images, and peripheral immune indicators for oral cancer prognosis. We firstly built a peripheral blood immune indicator-guided deep learning feature representation method for OCT images, and further integrated a multi-view prognostic radiomics model incorporating feature selection and logistic modeling. Thus, we can assess the prognostic impact of each indicator on oral cancer by quantifying OCT features. RESULTS: We collected 289 oral mucosal samples from 68 patients, yielding 1,445 OCT images. Using our deep radiomics-based prognosis model, it achieved excellent discrimination for oral cancer prognosis with the area under the receiver operating characteristic curve (AUC) of 0.886, identifying systemic immune-inflammation index (SII) as the most informative feature for prognosis prediction. Additionally, the deep learning model also performed excellent results with 85.26% accuracy and 0.86 AUC in classifying the SII risk. CONCLUSIONS: Our study effectively merged OCT imaging with peripheral blood immune indicators to create a deep learning-based model for inflammatory risk prediction in oral cancer. Additionally, we constructed a comprehensive multi-view radiomics model that utilizes deep learning features for accurate prognosis prediction. The study highlighted the significance of the SII as a crucial indicator for evaluating patient outcomes, corroborating our clinical statistical analyses. This integration underscores the potential of combining imaging and blood indicators in clinical decision-making. TRIAL REGISTRATION: The clinical trial associated with this study was prospectively registered in the Chinese Clinical Trial Registry with the trial registration number (TRN) ChiCTR2200064861. The registration was completed on 2021.
Assuntos
Aprendizado Profundo , Neoplasias Bucais , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/patologia , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , RadiômicaRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) is the predominant form of head and neck cancer, often diagnosed at late stages, resulting in a poor prognosis. Recent studies indicate a potential association between OSCC and microbial presence. Microorganisms have been identified in various tumors and lesions, including OSCC and oral potentially malignant disorders (OPMDs). Intralesional microbiota are considered important components of the tumor microenvironment (TME) and may contribute to carcinogenesis. METHODS: Sources were collected through thorough searches of databases PubMed and Embase. The review focused on microbial characteristics, potential origins, and their impact on cancer progression. RESULTS: Bacteria display varying abundance and diversity throughout the stages of OSCC and OPMDs. Intraleisional bacteria may have diverse sources, including not only oral plaque and saliva but also potentially the gut. Intralesional bacteria have both pro-carcinogenic and anti-carcinogenic effects, affecting processes like cell proliferation, invasion, and immune response. CONCLUSIONS: Intralesional microbiota are crucial in OSCC and OPMDs, influencing both disease progression and treatments. Despite their significance, challenges like inconsistent sampling and microbial identification remain. Future research is required to fully understand their role and improve clinical applications.
Assuntos
Progressão da Doença , Neoplasias Bucais , Microambiente Tumoral , Humanos , Neoplasias Bucais/microbiologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/microbiologia , Carcinoma de Células Escamosas/patologia , Microbiota , Bactérias , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Background: Oral cancer, a malignancy that is prevalent worldwide, is often diagnosed at an advanced stage. MicroRNAs (miRNAs) in circulating exosomes have emerged as promising cancer biomarkers. The role of miRNA let-7c-5p in oral cancer remains underexplored, and its potential involvement in tumorigenesis warrants comprehensive investigation. Methods: Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content. Isolation of the exosomes was confirmed through transmission electron microscopy. Quantitative PCR was used to assess the miRNA profiles. The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability, migration, and invasion were analyzed via CCK-8 and Transwell assays. Moreover, we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes. Results: let-7c-5p was upregulated in serum-derived exosomes of patients with oral cancer. Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative, migratory, and invasive capacities, and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness. Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes. We further identified TAGLN as a direct target of let-7c-5p, which has been implicated in modulating the oncogenic potential of oral cancer cells. Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells. Conclusion: Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression, highlighting its potential as a diagnostic and therapeutic strategy.
Assuntos
Movimento Celular , Proliferação de Células , Exossomos , MicroRNAs , Neoplasias Bucais , Humanos , Exossomos/genética , Exossomos/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , MicroRNAs/genética , Movimento Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Masculino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Invasividade NeoplásicaRESUMO
Oral squamous cell carcinoma (OSCC) is one of the most prevalent forms of head and neck squamous cell carcinomas (HNSCC) with a poor overall survival rate (about 50%), particularly in cases of metastasis. RNA-based cancer biomarkers are a relatively advanced concept, and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies. This review underlines the function of long non-coding RNAs (lncRNAs) in the OSCC and its subsequent clinical implications. LncRNAs, a class of non-coding RNAs, are larger than 200 nucleotides and resemble mRNA in numerous ways. However, unlike mRNA, lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA, RNA, proteins, or microRNAs depending on concentration and localization in cells. Upregulation of oncogenic lncRNAs and down-regulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers. Targeted inhibition of candidate oncogenic lncRNAs or over-expression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models. The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity. This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival, proliferation, invasion, migration, metastasis, angiogenesis, metabolism, epigenetic modification, tumor immune microenvironment, and drug resistance. Subsequently, we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems, providing details on ongoing research and outlining potential future directions for advancements in this field. In essence, this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.
Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Lymph node metastasis (LNM) is a typical marker in oral squamous cell carcinoma (OSCC) indicating poor prognosis. Pathological examination by artificial image acquisition and analysis, as the main diagnostic method for LNM, often takes a week or longer which may cause great anxiety of the patient and also retard timely treatment. However, there are few efficient fast LNM diagnosis methods in clinical applications currently. Our previous study profiled the proteomics of extracellular vesicles (EVs) derived from postoperative drainage fluid (PDF) and showed the potential of detecting specific EVs that expressed aspartate ß-hydroxylase (ASPH) for LNM diagnosis in OSCC patients. Considering that the analysis of ASPH+ PDF-EVs is challenging due to their low abundance (counting less than 10% of total EVs in PDF) and the complex EV isolation process of ultra-centrifugation, we developed a facile platform containing two microfluidic chips filled with antibody-modified microbeads to isolate ASPH+ PDF-EVs, with both the capture and retrieval rate reaching around 90%. Clinical sample analysis based on our method revealed that a mean of 6 × 106 /mL ASPH+ PDF-EVs could be isolated from LNM+ OSCC patients compared to 2.5 × 106 /mL in LNM- OSCC ones. When combined with enzyme-linked immunosorbent assay (ELISA) technique that was commonly used in clinical laboratories in hospitals, this microfluidic platform could precisely distinguish postoperative OSCC patients with LNM or not in several hours, which were validated by a double-blind test containing 6 OSCC patients. We believe this strategy has promise for early diagnosis of LNM in postoperative OSCC patients and finally helps guiding timely and reasonable treatment in clinic.
Assuntos
Vesículas Extracelulares , Metástase Linfática , Neoplasias Bucais , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Microfluídica/métodos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Dispositivos Lab-On-A-Chip , Masculino , Período Pós-Operatório , Pessoa de Meia-Idade , Drenagem/métodosRESUMO
Oral potentially malignant disorders (OPMDs) with genomic alterations have a heightened risk of evolving into oral squamous cell carcinoma (OSCC). Currently, genomic data are typically obtained through invasive tissue biopsy. However, brush biopsy is a non-invasive method that has been utilized for identifying dysplastic cells in OPMD but its effectiveness in reflecting the genomic landscape of OPMDs remains uncertain. This pilot study investigates the potential of brush biopsy samples in accurately reconstructing the genomic profile and tumor evolution in a patient with both OPMD and OSCC. We analyzed single nucleotide variants (SNVs), copy number aberrations (CNAs), and subclonal architectures in paired tissue and brush biopsy samples. The results showed that brush biopsy effectively captured 90% of SNVs and had similar CNA profiles as those seen in its paired tissue biopsies in all lesions. It was specific, as normal buccal mucosa did not share these genomic alterations. Interestingly, brush biopsy revealed shared SNVs and CNAs between the distinct OPMD and OSCC lesions from the same patient, indicating a common ancestral origin. Subclonal reconstruction confirmed this shared ancestry, followed by divergent evolution of the lesions. These findings highlight the potential of brush biopsies in accurately representing the genomic profile of OPL and OSCC, proving insight into reconstructing tumor evolution.
Assuntos
Neoplasias Bucais , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Biópsia/métodos , Variações do Número de Cópias de DNA , Polimorfismo de Nucleotídeo Único , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Projetos Piloto , Masculino , Pessoa de Meia-Idade , Genômica/métodos , Feminino , Mucosa Bucal/patologiaRESUMO
BACKGROUND: Long noncoding RNAs (lncRNAs) are widely involved in cancer development and progression, but the functions of most lncRNAs have not yet been elucidated. Metastasis is the main factor restricting the therapeutic outcomes of various cancer types, including oral squamous cell carcinoma (OSCC). Therefore, exploring the key lncRNAs that regulate OSCC metastasis and elucidating their molecular mechanisms will facilitate the development of new strategies for effective OSCC therapy. METHODS: We analyzed the lncRNA expression profiles of tumor tissues from OSCC patients with and without cervical lymph node metastasis, and OSCC cell lines. We revealed high expression of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC patient tumor tissues with lymph node metastasis and highly metastatic OSCC cell lines. The effects of lncOCMRL1 knockdown on the invasion, migration and proliferation abilities of OSCC cells were explored through qRT-PCR, Transwell, colony formation, and cell proliferation experiments. The mechanism by which lncOCMRL1 promotes OSCC metastasis and proliferation was explored through RNA pull-down, silver staining, mass spectrometry, RIP, and WB experiments. To increase its translational potential, we developed a reduction-responsive nanodelivery system to deliver siRNA for antitumor therapy. RESULTS: We determined that lncOCMRL1 is highly expressed in OSCC metastatic tumor tissues and cells. Functional studies have shown that high lncOCMRL1 expression can promote the growth and metastasis of OSCC cells both in vivo and in vitro. Mechanistically, lncOCMRL1 could induce epithelial-mesenchymal transition (EMT) via the suppression of RRM2 ubiquitination and thereby promote the proliferation, invasion, and migration of OSCC cells. We further constructed reduction-responsive nanoparticles (NPs) for the systemic delivery of siRNAs targeting lncOCMRL1 and demonstrated their high efficacy in silencing lncOCMRL1 expression in vivo and significantly inhibited OSCC tumor growth and metastasis. CONCLUSIONS: Our results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.
Assuntos
Proliferação de Células , Transição Epitelial-Mesenquimal , Neoplasias Bucais , RNA Longo não Codificante , Ribonucleosídeo Difosfato Redutase , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Camundongos , Animais , Feminino , Transição Epitelial-Mesenquimal/genética , Ribonucleosídeo Difosfato Redutase/metabolismo , Ribonucleosídeo Difosfato Redutase/genética , Masculino , Linhagem Celular Tumoral , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Metástase Neoplásica , Movimento Celular , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Pessoa de Meia-Idade , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , Metástase LinfáticaRESUMO
BACKGROUND: The role of Mediator complex subunit 1 (MED1), a pivotal transcriptional coactivator implicated in diverse biological pathways, remains unexplored in the context of oral squamous cell carcinoma (OSCC). This study aims to elucidate the contributory mechanisms and potential impact of MED1 on the progression of OSCC. METHODS: The expression and clinical significance of MED1 in OSCC tissues were evaluated through the bioinformatics analyses. The effects of MED1 on the biological behavior of OSCC cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) assay, bioinformatic analysis, CD8+ T cell isolation experiment, coculture experiment, enzyme-linked immunosorbent assay (ELISA), and flow cytometric analysis were employed to elucidate the underlying mechanism through which MED1 operates in the progression of OSCC. RESULTS: MED1 exhibited upregulation in both OSCC tissues and multiple OSCC cell lines, which correlated with decreased overall survival in patients. In vitro experiments demonstrated that knockdown of MED1 in metastatic OSCC cell lines SCC-9 and UPCI-SCC-154 hindered cell migration and invasion, while overexpression of MED1 promoted these processes. Whereas, MED1 knockdown had no impact on proliferation of cell lines mentioned above. In vivo studies further revealed that downregulation of MED1 effectively suppressed distant metastasis in OSCC. Mechanistically, MED1 enhanced the binding of transcription factors c-Jun and c-Fos to the matrix metalloprotein 9 (MMP9) promoters, resulting in a significant upregulation of MMP9 transcription. This process contributes to the migration and invasion of SCC-9 and UPCI-SCC-154 cells. Furthermore, MED1 modulated the expression of programmed death-ligand 1 (PD-L1) through the Notch signaling pathway, consequently impacting the tumor-killing capacity of CD8+ T cells in the tumor microenvironment. CONCLUSIONS: Our findings indicate that MED1 plays a pivotal role in OSCC progression through the activation of MMP9 transcription and suppression of CD8+ T cell antitumor immunity, suggesting that MED1 may serve as a novel prognostic marker and therapeutic target in OSCC.
Assuntos
Linfócitos T CD8-Positivos , Carcinoma de Células Escamosas , Progressão da Doença , Metaloproteinase 9 da Matriz , Subunidade 1 do Complexo Mediador , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/imunologia , Neoplasias Bucais/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Animais , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Subunidade 1 do Complexo Mediador/metabolismo , Subunidade 1 do Complexo Mediador/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , PrognósticoRESUMO
BACKGROUND: Despite its low sensitivity (approximately 30%), squamous cell carcinoma (SCC) antigen is commonly utilized as a serum tumor marker for oral SCC (OSCC) in clinical settings. The objective of this research was to identify novel biomarkers for OSCC. METHODS: Initially, we performed microarray analysis to evaluate the gene expression signatures of primary OSCC and normal oral mucosal tissues. Our findings showed the C-X-C motif chemokine ligand 13 (CXCL13) to be a promising novel biomarker as it was consistently overexpressed in primary OSCC tissues, a conclusion corroborated by polymerase chain reaction results. Subsequently, we measured serum CXCL13 levels in 125 patients with OSCC using a sandwich enzyme-linked immunosorbent assay and compared the results with those of 29 healthy individuals. RESULTS: Remarkably, the levels of serum CXCL13 were consistently elevated in patients with OSCC, and the high expression of serum CXCL13 was notably associated with tumor size and neck lymph node metastasis. Patients with advanced OSCC with high-serum CXCL13 levels exhibited poor prognosis regarding both overall and disease-free survival. Finally, spatial transcriptome analysis revealed CXCL13 and CD8 expressions within tumor area clusters but not in adjacent normal areas, suggesting specific overexpression of CXCL13 in primary OSCC tissues. CONCLUSION: These findings imply that serum CXCL13 holds diagnostic and prognostic value, showing promise as a novel biomarker for OSCC.
Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Quimiocina CXCL13 , Neoplasias Bucais , Humanos , Quimiocina CXCL13/sangue , Quimiocina CXCL13/genética , Neoplasias Bucais/sangue , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Perfilação da Expressão Gênica , Estadiamento de Neoplasias , Metástase Linfática , Regulação Neoplásica da Expressão GênicaRESUMO
Objective: To investigate the effect of anatomical unit resection on the overall survival rate of patients with T4 stage posterior buccal carcinoma. Methods: We conducted a retrospective study on 79 patients with T4 stage posterior buccal squamous cell carcinoma underwent radical surgery for buccal mucosa cancer and reconstruction with free anterolateral thigh flap in the Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University from March 2014 to December 2019. The 74 patients were males and the 5 patients were females, aged from 28 to 72 years old. The 40 patients in control group underwent traditional extended resection (1.5-2.0 cm safe margin), and 39 patients in the experimental group underwent anatomical unit resection. The clinicopathological parameters of patients were collected and followed up regularly. The overall survival rate was assessed by Log-rank and Cox proportional risk regression model. Multivariate analysis was performed by linear regression model. Results: There were significant differences between experimental group and control group in overall survival rates (61.53% vs 27.50%, χ2=6.624, P=0.010) and local disease control rates (74.36% vs 27.50%, χ2=17.350, P<0.001). Multiple linear regression analysis showed that local disease control rate was significantly correlated with anatomical unit resection (t=3.880, P<0.001) and lymph node metastasis (t=2.619, P=0.011), and also Cox proportional hazards regression model analysis identified that overall survival rate was significantly correlated with anatomical unit resection (Z=2.421, P=0.016) and lymph node metastasis (Z=2.793, P=0.005). Conclusion: For posterior buccal carcinoma with multiple anatomical units involved, anatomical unit resection can significantly reduce local recurrence and improve overall survival rate of patients.