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OBJECTIVES: To investigate risk factors associated with occult lymph node metastases (ONM) and skip metastasis in early-stage oral tongue squamous cell carcinoma (OTSCC) patients. Meanwhile, to analyze the contribution of metastatic nodes to survival outcomes. MATERIALS AND METHODS: 544 OTSCC patients who were clinically staged T1-T2N0 with pathologic results from May 2018 to January 2024 were enrolled. Those with ONM were divided into subgroups with or without skip metastasis. Clinical, laboratorial, radiological and pathological factors between groups were analyzed by using univariate analysis and multivariate logistic analysis. The association of tumor growth behavior with the metastatic pattern of lymph nodes was summarized. Additionally, disease free survival (DFS) among different groups were compared using Kaplan-Meier analysis. RESULTS: Tumor growth behavior was associated with ONM. Tumor thickness with a threshold of 6.4 mm was not inferior to histological depth of invasion in predicting ONM. Only 1.3% of patients had nodal involvement of neck level IV or V. The DFS of patients with ONM were significantly reduced than those without ONM (P < 0.001). The DFS between patients with and without skip metastasis exhibited no statistical significance(P = 0.246). The 1-year, 2-year recurrence rates of patients with or without ONM were 31.9%, 37.5%, 10.1% and 14.0%, correspondingly. CONCLUSIONS: Tumor thickness with a threshold of 6.4 mm could be used as a preoperative predictor for ONM. Elective neck dissection of level I - III might be sufficient for early stage OTSCC patients. OTSCC patients with ONM should be closely observed during the first 2 years after surgery. CLINICAL RELEVANCE: The risk of ONM in early stage OTSCC patients might be predicted by tumor thickness calculated on MR imaging. Elective neck dissection of level I - III could remove micrometastases timely and effectively.

Asunto(s)

Carcinoma de Células Escamosas , Metástasis Linfática , Estadificación de Neoplasias , Neoplasias de la Lengua , Humanos , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/cirugía , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Anciano , Adulto , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Disección del Cuello , Anciano de 80 o más Años , Invasividad Neoplásica

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BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) often presents with aggressive clinical behaviour that may require multimodality treatment based on reliable prognostication. We aimed to evaluate the prognostic ability of five online web-based tools to predict the clinical behaviour of OTSCC resection and biopsy samples. METHODS: A total of 135 OTSCC resection cases and 33 OTSCC biopsies were included to predict recurrence and survival. Area under the receiver operating characteristic curves (AUC), χ2 tests, and calibration plots constructed to estimate the prognostic power of each tool. RESULTS: The tool entitled 'Prediction of risk of Locoregional Recurrences in Early OTSCC' presented an accuracy of 82%. The tool, 'Head & Neck Cancer Outcome Calculator' for 10-year cancer-related mortality had an accuracy 77% and AUC 0.858. The other tool entitled 'Cancer Survival Rates' for 5-year mortality showed an accuracy of 74% and AUC of 0.723. For biopsy samples, 'Cancer Survival Prediction Calculators' predicted the recurrence free survival with an accuracy of 70%. CONCLUSIONS: Web-based tools can aid in clinical decision making of OTSCC. Three of five online web-based tools could predict recurrence risk and cancer-related mortality in resected OTSCC and one tool could help in clinical decision making for biopsy samples.

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OBJECTIVES: Previous studies have demonstrated that obesity may impact the efficacy of anti-PD1 therapy, but the underlying mechanism remains unclear. In this study, our objective was to determine the prognostic value of obesity in patients with oral tongue squamous cell carcinoma (OTSCC) treated with pembrolizumab and establish a subtype based on fatty acid metabolism-related genes (FAMRGs) for immunotherapy. MATERIALS AND METHODS: We enrolled a total of 56 patients with OTSCC who underwent neoadjuvant anti-PD1 therapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, and immunohistochemistry staining were performed. Additionally, we acquired the gene expression profiles of pan-cancer samples and conducted GSEA and KEGG pathway analysis. Moreover, data from TCGA, MSigDB, UALCAN, GEPIA and TIMER were utilized to construct the FAMRGs subtype. RESULTS: Our findings indicate that high Body Mass Index (BMI) was significantly associated with improved PFS (HR = 0.015; 95% CI, 0.001 to 0.477; p = 0.015), potentially attributed to increased infiltration of PD1 + T cells. A total of 91 differentially expressed FAMRGs were identified between the response and non-response groups in pan-cancer patients treated with immunotherapy. Of these, 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) were found to affect PD-1 expression and T cell infiltration in HNSCC, which may impact the efficacy of anti-PD1 therapy. CONCLUSION: This study demonstrates that obesity serves as a robust prognostic predictor for patients with OTSCC undergoing neoadjuvant anti-PD1 therapy. Furthermore, the expression of 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) plays a pivotal role in the context of anti-PD1 therapy and deserves further investigation.

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Inhibidores de Puntos de Control Inmunológico , Terapia Neoadyuvante , Obesidad , Neoplasias de la Lengua , Humanos , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/inmunología , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/mortalidad , Neoplasias de la Lengua/genética , Femenino , Masculino , Terapia Neoadyuvante/métodos , Obesidad/metabolismo , Obesidad/complicaciones , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Pronóstico , Anciano , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Anticuerpos Monoclonales Humanizados/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Adulto , Índice de Masa Corporal , Biomarcadores de Tumor/metabolismo

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BACKGROUND: The purpose of this study was to provide further insights into whether age and/or sex are associated with prognosis in oral tongue squamous cell carcinoma. METHODS: This was a retrospective cohort study utilizing hospital registry data from 2006 to 2016 obtained from the National Cancer Database. Identified patients were divided into various cohorts based on age, sex, and staging. A descriptive analysis was performed using chi-square tests and overall survival rates were estimated using Kaplan-Meier method. RESULTS: A total of 17 642 patients were included in the study. The 5-year overall survival rates were 82.0% (95% CI: 79.8%-84.0%) in younger patients versus 67.5% (95% CI: 66.7%-68.3%, p-value <0.0001) older patients. The median overall survival for females was 143.4 months (95% CI: 133.2-NA) versus 129.8 (95% CI: 125.4-138.7, p-value <0.0001) in males. CONCLUSIONS: Our analysis suggests that younger age and female sex are both predictors of improved survival in oral tongue squamous cell carcinoma.

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Carcinoma de Células Escamosas , Estadificación de Neoplasias , Neoplasias de la Lengua , Humanos , Masculino , Femenino , Neoplasias de la Lengua/mortalidad , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/terapia , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Factores de Edad , Factores Sexuales , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Adulto , Tasa de Supervivencia , Pronóstico , Estudios de Cohortes , Anciano de 80 o más Años , Estimación de Kaplan-Meier , Sistema de Registros , Estados Unidos/epidemiología

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PURPOSE: This study aimed to compare the radiological tumor (T)-category using multiparametric MRI with the pathological T category in patients with oral tongue squamous cell carcinoma (OTSCC) and to examine which is a better predictor of prognosis. METHODS: This retrospective study included 110 consecutive patients with surgically resected primary OTSCC who underwent preoperative contrast-enhanced MRI. T categories determined by maximum diameter and depth of invasion were retrospectively assessed based on the pathological specimen and multiparametric MRI. The MRI assessment included the axial and coronal T1-weighted image (T1WI), axial T2-weighted image (T2WI), coronal fat-suppressed T2WI, and axial and coronal fat-suppressed contrast-enhanced T1WI (CET1WI). Axial and coronal CET1WI measurements were divided into two groups: measurements excluding peritumoral enhancement (MEP) and measurements including peritumoral enhancement. The prognostic values for recurrence and disease-specific survival after radiological and pathological T categorization of cases into T1/T2 and T3/T4 groups were compared. RESULTS: The T category of MEP on coronal CET1WI was the most relevant prognostic factor for recurrence [hazard ratio (HR) = 3.30, p = 0.001] and the HR was higher than the HR for pathological assessment (HR = 2.26, p = 0.026). The T category determined by MEP on coronal CET1WI was also the most relevant prognostic factor for disease-specific survival (HR = 3.12, p = 0.03), and the HR was higher than the HR for pathological assessment (HR = 2.02, p = 0.20). CONCLUSION: The T category determined by MEP on the coronal CET1WI was the best prognostic factor among all radiological and pathological T category measurements.

Asunto(s)

Carcinoma de Células Escamosas , Medios de Contraste , Imagen por Resonancia Magnética , Neoplasias de la Lengua , Humanos , Neoplasias de la Lengua/diagnóstico por imagen , Neoplasias de la Lengua/patología , Masculino , Femenino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Anciano , Imagen por Resonancia Magnética/métodos , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Adulto , Estadificación de Neoplasias , Anciano de 80 o más Años , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tasa de Supervivencia , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Invasividad Neoplásica

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Background: Oral cancer remains one of the most dreadful diseases in developing nations. Currently, there has been a rise in the prevalence of tongue squamous cell carcinoma (SCC), with a poor prognosis. The use of standard treatment approaches against oral cancer patients brings about several side effects. In recent years, nanomedicine has provided a versatile platform for developing new targeted therapeutic modalities. However, safety remains a concern in the synthesis of nanoparticles (NPs). Therefore, the present study aims to synthesize safer phytoconstituent-mediated gold NPs (AuNPs) utilizing leaf extracts of Annona muricata, where the biochemical components of the plant leaf act as the reducing and capping agents in the synthesis of NPs, and to evaluate its anti-cancer activity against SCC. Materials and Methods: In this in vitro experimental study, AuNPs were synthesized through an effective, simple, and ecologically sound green synthesis method. After characterization of these synthesized AuNPs, in vitro assays such as 3-(4, 5-dimethylthiazole2-yl)-2, 5-biphenyl tetrazolium bromide, wound healing, and clonogenic assays were carried out to investigate the anti-cancer potential of green synthesized AuNPs in the human tongue SCC cell line (SCC-15), and the possible mechanism of action was evaluated through gene and protein expression analysis of Bax, Bcl-2, and p53 genes. The results were expressed as mean ± standard deviation using Statistical Package for Social Sciences (SPSS) 20.0 software and Student's t-test was performed for experimental data. P ≤0.05 were considered statistically significant. Results: The in vitro assays demonstrated that the synthesized AuNPs are exhibiting anti-cancer activity by apoptosis of SCC-15 cells in a dose-dependent manner. Further, it also revealed a highly significant decrease in anti-apoptotic Bcl-2 gene expression, whereas pro-apoptotic genes p53 and Bax revealed a highly significant increase, which is statistically significant compared to the control (P < 0.05). Conclusion: Our findings demonstrated that the AuNPs synthesized from A. muricata leaf extract could act as a novel anticancer agent, particularly against SCC, after further scrutiny.

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Oral tongue squamous cell carcinoma (OTSCC) is the most common malignancy type among males across the world. However, analysis of molecular markers could be useful in detecting the early-stage OTSCC, which would allow optimal clinical treatments and prolong the survival rate of patients consequently. The study has the objective of detecting the role of salivary biomarkers based on gene promoter hypermethylation. Sample data from 45 OTSCC and normal groups were analyzed to exhibit the methylation levels of salivary biomarkers (TRH, FHIT, MGMT, p16, and RASSF1A). The specificity and sensitivity analysis of methylation biomarkers was conducted in addition to the receiver operating characteristic (ROC) curve for both early-stage and advanced OTSCC stages. Quantitative data findings showed the perfect sensitivity and specificity for TRH, MGMT, p16, and RASSF1A with 100%, and > 90%, respectively. In addition, the results indicated an inefficient area under curves (> 0.7) for these biomarkers to detect the OTSCC. There were no significant differences observed between TRH and FHIT and p16 and MGMT based on the Wilcoxon signed-rank test. The methylation statuses of genes TRH, RASSF1A, p16, and MGMT might become utilized as predictive biomarkers for clinical application in early diagnosis of OTSCC and noninvasive oral cancer screening.

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Biomarcadores de Tumor , Carcinoma de Células Escamosas , Metilación de ADN , Enzimas Reparadoras del ADN , Detección Precoz del Cáncer , Neoplasias de la Lengua , Proteínas Supresoras de Tumor , Humanos , Metilación de ADN/genética , Biomarcadores de Tumor/genética , Masculino , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/diagnóstico , Proteínas Supresoras de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/diagnóstico , Persona de Mediana Edad , Femenino , Enzimas Reparadoras del ADN/genética , Metilasas de Modificación del ADN/genética , Adulto , Anciano , Regiones Promotoras Genéticas/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Sensibilidad y Especificidad , Curva ROC , Proteínas de Neoplasias/genética , Ácido Anhídrido Hidrolasas/genética , Saliva/química

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Oral tongue squamous-cell carcinoma (OTSCC) is the most prevalent malignancy in the head and neck region. Lymphatic spread, particularly to cervical lymph nodes, significantly impacts 5-year survival rates, emphasizing the criticality of precise staging. Metastatic cervical lymph nodes can decrease survival rates by 50%. Yet, elective neck dissection (END) in T1-2 cN0 patients proves to be an overtreatment in around 80% of cases. To address this, sentinel lymph node biopsy (SLNB) was introduced, aiming to minimize postoperative morbidity. This study, conducted at the ENT and Maxillofacial Surgery department of the Istituto Nazionale Tumori in Naples, explores SLNB's efficacy in early-stage oral tongue squamous-cell carcinoma (OTSCC). From January 2020 to January 2022, 122 T1/T2 cN0 HNSCC patients were enrolled. Radioactive tracers and lymphoscintigraphy identified sentinel lymph nodes, aided by a gamma probe during surgery. Results revealed 24.6% SLN biopsy positivity, with 169 SLNs resected and a 21.9% positivity ratio. The study suggests SLNB's reliability for T1-2 cN0 OTSCC patient staging and early micrometastasis detection.

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Strong evidence has indicated that upregulation of chemokine (CC motif) ligand-2 (CCL2) expression and the presence of an inflammatory tumor microenvironment significantly contribute to the migratory and invasive properties of oral squamous cell carcinoma, specifically oral tongue squamous cell carcinoma (OTSCC). However, the precise epigenetic mechanism responsible for enhanced CCL2 expression in response to the inflammatory mediator tumor necrosis factor alpha (TNF-α) in OTSCC remains inadequately elucidated. We have demonstrated that the production of CCL2 can be induced by TNF-α, and this induction is mediated by the chromatin remodel protein BRG1. Through the use of a chromatin immunoprecipitation (ChIP) assay, we have found that BRG1 was involved in the recruitment of acetylated histones H3 and H4 at the CCL2 promoter, thereby activating TNF-α-induced CCL2 transcription. Furthermore, we have observed that recruitment of NF-κB p65 to the CCL2 promoter was increased following BRG1 overexpression and decreased after BRG1 knockdown in OTSCC cells. Our Re-ChIP assay has shown that BRG1 knockdown completely inhibits the recruitment of both acetylated histone H3 or H4 and NF-κB to the CCL2 promoter. In summary, the findings of our study demonstrate that BRG1 plays a significant role in mediating the production of CCL2 in OTSCC cells in response to TNF-α stimulation. This process involves the cooperative action of acetylated histone and NF-κB recruitment to the CCL2 promoter site. Our data suggest that BRG1 serves as a critical epigenetic mediator in the regulation of TNF-α-induced CCL2 transcription in OTSCC cells.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Lengua , Factor de Necrosis Tumoral alfa , Humanos , Carcinoma de Células Escamosas/genética , Quimiocina CCL2/metabolismo , Epigénesis Genética , Histonas/metabolismo , Neoplasias de la Boca , FN-kappa B/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Neoplasias de la Lengua/genética , Microambiente Tumoral , Factor de Necrosis Tumoral alfa/metabolismo

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Introduction: The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined. Methods: We assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively. Results: MUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells in vitro, in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. Conclusion: The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de la Lengua , Humanos , Animales , Ratones , Carcinoma de Células Escamosas/terapia , Neoplasias de la Lengua/terapia , Células Asesinas Naturales , Línea Celular , Lengua/metabolismo , Mucina-1/genética , Mucina-1/metabolismo

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Lymph node metastasis (LNM) is one of the common features of oral tongue squamous cell carcinoma (OTSCC). LNM is also taken as a sign of advanced OTSCC and poor survival rate. Recently, single-cell RNA sequencing has been applied in investigating the heterogeneity of tumor microenvironment and discovering the potential biomarkers for helping the diagnosis and prognosticating. Pathogenesis of LNM in OTSCC remains unknown. Specifically, cancer-associated fibroblasts (CAFs) and epithelial tumor cells could foster the progression of tumors. Thus, in this study, we aimed to comprehensively analyze the roles of subpopulations of CAFs and epithelial tumor cells in lymph node metastatic OTSCC using the integration of OTSCC single-cell RNA sequencing datasets. Four distinct subtypes of CAFs, namely vascular CAFs, myofibroblast CAFs, inflammatory CAFs, and growth arrest CAFs were successfully discovered in LNM tumor and confirmed the roles of GAS and PTN pathways in the progression of tumor metastasis. In addition, NKAIN2+ epithelial cells and FN1+ epithelial cells specifically exhibited an upregulation of PTN, NRG, MIF, and SPP1 signaling pathways in the metastatic OTSCC. In doing so, we put forth some potential biomarkers that could be utilized for the purpose of diagnosing and prognosticating OTSCC during its metastatic phase and tried to confirm by immunofluorescence assays.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Lengua , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/patología , Fibroblastos/patología , Células Epiteliales/patología , Biomarcadores , Metástasis Linfática/patología , Neoplasias de Cabeza y Cuello/patología , Análisis de Secuencia de ARN , Microambiente Tumoral

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Objective:To investigate the mechanism of interferon γ(IFN-γ)combined with ferroptosis inducer Erastin in the inhibi-tion of the growth of oral tongue squamous cell carcinoma(OTSCC).Methods:The expression of SLC7A11 in OTSCC was studied by bioinformatics analysis and immunohistochemical staining.SLC7A11 gene in OTSCC CAL-27 cells was knocked out by CRISPR-CAS9,and the survival rate of WT and SLC7A11 KO cells treated with Erastin was measured by MTT assay.Glutathione kit,lipid oxidation kit and flow cytometry were used to detect the changes of lipid peroxides in the cells treated with Erastin.After 24 h pretreatment with IFN-γ,MTT assay was used to detect the changes of cell sensitivity to Erastin,and the changes in lipid peroxides were detected by glu-tathione kits,lipid oxidation kits and flow cytometry.Results:Bioinformatics analysis and immunohistochemical staining showed that SLC7A11 was highly expressed in OTSCC.SLC7A11 KO CAL-27 cells were more sensitive to Erastin than WT cells.The GSH content of SLC7A11 KO cells was lower than that of WT cells,and the lipid peroxide content was higher than that of WT cells after treatment with Erastin.IFN-γ increased cell sensitivity to Erastin,decreased GSH content and increased lipid peroxides content in the cells.Conclusion:IFN-γ can reduce GSH and increase MDA and Lipid ROS levels by degrading SLC7A11,this increases the sensitivity of OTSCC to Erastin.

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BACKGROUND: The purpose of this study was to explore preliminary the performance of radiomics machine learning models based on multimodal MRI to predict the risk of cervical lymph node metastasis (CLNM) for oral tongue squamous cell carcinoma (OTSCC) patients. METHODS: A total of 400 patients were enrolled in this study and divided into six groups according to the different combinations of MRI sequences. Group I consisted of patients with T1-weighted images (T1WI) and FS-T2WI (fat-suppressed T2-weighted images), group II consisted of patients with T1WI, FS-T2WI, and contrast enhanced MRI (CE-MRI), group III consisted of patients with T1WI, FS-T2WI, and T2-weighted images (T2WI), group IV consisted of patients with T1WI, FS-T2WI, CE-MRI, and T2WI, group V consisted of patients with T1WI, FS-T2WI, T2WI, and apparent diffusion coefficient map (ADC), and group VI consisted of patients with T1WI, FS-T2WI, CE-MRI, T2WI, and ADC. Machine learning models were constructed. The performance of the models was compared in each group. RESULTS: The machine learning model in group IV including T1WI, FS-T2WI, T2WI, and CE-MRI presented best prediction performance, with AUCs of 0.881 and 0.868 in the two sets. The models with CE-MRI performed better than the models without CE-MRI(I vs. II, III vs. IV, V vs. VI). CONCLUSIONS: The radiomics machine learning models based on CE-MRI showed great accuracy and stability in predicting the risk of CLNM for OTSCC patients.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Lengua , Humanos , Metástasis Linfática , Carcinoma de Células Escamosas de Cabeza y Cuello , Carcinoma de Células Escamosas/diagnóstico por imagen , Radiómica , Neoplasias de la Lengua/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Aprendizaje Automático , Estudios Retrospectivos

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Background: Tongue tumors show intra and inter-tumoral heterogenicity with high incidence, relapse and mortality rates necessitating further research.  Recurrence/metastasis that occurs  after surgical resection of primary cancer is often the reason for poor survival in these patients.  Lymph nodes are the most common site of metastasis in tongue tumors. Therefore, premetastatic molecular changes can be best evaluated in lymph nodes which may epitomize the earliest events in the metastasis cascades. The presence of circulating tumor cells(CTCs) in the absence of nodal disease (N0) may represent tumor aggressiveness, suggesting an immune escape which may have high metastatic potential. This trial  was developed  to investigate the earliest pre-metastatic changes which may regulate tumor dormancy and predict metastasis. A better understanding of organotropism or pre-metastatic changes can help in theragnostic, thereby  preventing the outbreak of overt metastasis.  Methods: A single-institutional prospective observational cohort study. This trial will be conducted at a tertiary care Centre (Amrita Institute of Medical Sciences Kochi).  Eligible patients will be enrolled after obtaining informed consent. The dissected lymph nodes will  be subjected to histopathological and immunohistochemical analyses for premetastatic niche (PMN) formation. In addition, circulating tumor cells will be evaluated before treatment and 6 months after treatment. The patients will be followed  up for a period of two years to correlate the findings with the recurrence-free survival. Expected results:  The pre-metastatic changes, if detected will  be  a predictive biomarker. It may help to define future drug targets for metastasis chemoprevention   . CTCs may  define the tumor aggressiveness ,there by  prognostication  and helps in better disease management. Ethics and dissemination: The study has received the following approval: Ethics Committee of Amrita School of Medicine (ECASM-AIMS-2022-048).Trial Registered Prospectively( CTRI/2022/03/041256 ) on 22/03/2022 under Clinical Trial Registry of India.

Asunto(s)

Neoplasias de la Boca , Células Neoplásicas Circulantes , Neoplasias de la Lengua , Humanos , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/cirugía , Estudios Prospectivos , Células Neoplásicas Circulantes/patología , Recurrencia Local de Neoplasia , Ganglios Linfáticos/patología

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BACKGROUND: 3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices. METHODS: We used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties. RESULTS: OTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared with Myogel and h-LG. The highest number of unique adhesion-related proteins was present in h-LG. CONCLUSIONS: We demonstrated that human pre-metastatic neck lymph node-derived matrix is suitable for studying metastatic OTSCC cells. As a whole-protein extract, h-LG provides new opportunities for in vitro carcinoma cell culture experiments.

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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Neoplasias de la Lengua , Humanos , Animales , Porcinos , Carcinoma de Células Escamosas/patología , Proteómica , Neoplasias de la Lengua/patología , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Ganglios Linfáticos/patología , Microambiente Tumoral/fisiología

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OBJECTIVE: We aimed to develop a 5-year overall survival prediction model for patients with oral tongue squamous cell carcinoma based on machine learning methods. SUBJECTS AND METHODS: The data were obtained from electronic medical records of 224 OTSCC patients at the PLA General Hospital. A five-year overall survival prediction model was constructed using logistic regression, Support Vector Machines, Decision Tree, Random Forest, Extreme Gradient Boosting, and Light Gradient Boosting Machine. Model performance was evaluated according to the area under the curve (AUC) of the receiver operating characteristic curve. The output of the optimal model was explained using the Python package (SHapley Additive exPlanations, SHAP). RESULTS: After passing through the grid search and secondary modeling, the Light Gradient Boosting Machine was the best prediction model (AUC = 0.860). As explained by SHapley Additive exPlanations, N-stage, age, systemic inflammation response index, positive lymph nodes, plasma fibrinogen, lymphocyte-to-monocyte ratio, neutrophil percentage, and T-stage could perform a 5-year overall survival prediction for OTSCC. The 5-year survival rate was 42%. CONCLUSION: The Light Gradient Boosting Machine prediction model predicted 5-year overall survival in OTSCC patients, and this predictive tool has potential prognostic implications for patients with OTSCC.

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Carcinoma de Células Escamosas , Hemostáticos , Neoplasias de la Lengua , Humanos , Fibrinógeno , Aprendizaje Automático

RESUMEN

This retrospective study addressed the role of oral potentially malignant disorders and the presence of intraepithelial Candida hyphae in the carcinogenesis of the oral tongue squamous cell carcinoma and its association with smoking, alcohol consumption, and oral inflammatory burden. The medical records of 183 subjects diagnosed with oral tongue squamous cell carcinoma at the Helsinki University Hospital were investigated. Preceding oral lichen planus, lichenoid reaction, and leukoplakia diagnosis were recorded. Further, the data on Candida hyphae in histological samples as an indicator of oral candidiasis, oral inflammatory burden, smoking, and alcohol consumption were recorded and analyzed. The histopathological diagnosis of oral lichen planus/lichenoid reaction (p < 0.001) and the presence of Candida hyphae (p = 0.005) were associated significantly with female gender. Oral lichen planus/lichenoid reaction patients were less often smokers than patients without these lesions. Candida hyphae were more often recorded in patients without alcohol use (p = 0.012). Oral lichen planus/lichenoid reaction and Candida hyphae in histological samples were associated with female gender and lower levels of typical risk factors, such as alcohol use and smoking, in oral tongue squamous cell carcinoma patients. Therefore, these patients should be well monitored despite a potential lack of the classical risk factors of oral carcinoma.

RESUMEN

OBJECTIVE: Disease metabolomes have been studied for identifying diagnostic and predictive biomarkers of pathology. Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent subtypes of head and neck squamous cell carcinoma, yet the profile and diagnostic value of its tissue metabolite are unclear. SUBJECTS AND METHODS: Tumor tissue samples and matched normal mucosal tissue samples were collected from 40 OTSCC patients. Untargeted metabolic analysis by liquid chromatography-mass spectrometry/mass spectrometry, in positive and negative ion modes, was used to identify dysregulated metabolites in OTSCC. Further, utilizing LASSO regression and receiver operating characteristic analyses, biomarker metabolites were selected and validated, and a diagnostic model was established. RESULTS: One hundred and ninety metabolites were detected. The OTSCC had a total of 89 dysregulated metabolites, of which 73 were elevated. A diagnostic panel of nine metabolites was subsequently created that could accurately identify OTSCC with 100% sensitivity of 100%, 100% specificity and an AUC of 1.00. CONCLUSIONS: This study identified distinct metabolic characteristics of OTSCC and established a diagnostic model. Our research also contributes to the investigation of the pathogenesis of OTSCC.

RESUMEN

OBJECTIVES: To investigate the usefulness of harmonized 18F-FDG-PET/CT parameters for predicting the postoperative recurrence and prognosis of oral tongue squamous cell carcinoma (OTSCC). METHODS: We retrospectively analyzed the cases of 107 OTSCC patients who underwent surgical resection at four institutions in Japan in 2010-2016 and evaluated the harmonized PET parameters of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumor as the pSUVmax, pMTV, and pTLG. For lymph node metastasis, we used harmonized PET parameters of nodal-SUVmax, nodal-total MTV (tMTV), and nodal-total TLG (tTLG). The associations between the harmonized PET parameters and the patients' relapse-free survival (RFS) and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox proportional hazard regression analysis for model 1 (preoperative stage) and model 2 (preoperative + postoperative stages). RESULTS: The harmonized SUVmax values were significantly lower than those before harmonization (p=0.012). The pSUVmax was revealed as a significant preoperative risk factor for RFS and OS. Nodal-SUVmax, nodal-tMTV, and nodal-tTLG were significant preoperative risk factors for OS. The combination of pSUVmax + nodal-SUVmax significantly stratified the patients into a low-risk group (pSUVmax <3.97 + nodal-SUVmax <2.85 or ≥2.85) and a high-risk group (pSUVmax ≥3.97 + nodal-SUVmax <2.85 or pSUVmax ≥3.97 + nodal-SUVmax ≥2.85) for recurrence and prognosis (RFS: p=0.001; OS: p<0.001). CONCLUSIONS: The harmonized pSUVmax is a significant prognostic factor for the survival of OTSCC patients. The combination of pSUVmax and nodal-SUVmax identified OTSCC patients at high risk for recurrence and poor prognosis at the preoperative stage.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Lengua , Humanos , Fluorodesoxiglucosa F18/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Radiofármacos , Carcinoma de Células Escamosas de Cabeza y Cuello , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/cirugía , Estudios Retrospectivos , Neoplasias de la Lengua/diagnóstico por imagen , Neoplasias de la Lengua/cirugía , Tomografía de Emisión de Positrones

RESUMEN

Despite diagnostic advancements, the development of reliable prognostic systems for assessing the risk of cancer recurrence still remains a challenge. In this study, we developed a novel framework to generate highly representative machine-learning prediction models for oral tongue squamous cell carcinoma (OTSCC) cancer recurrence. We identified cases of 5- and 10-year OTSCC recurrence from the SEER database. Four classification models were trained using the H2O ai platform, whose performances were assessed according to their accuracy, recall, precision, and the area under the curve (AUC) of their receiver operating characteristic (ROC) curves. By evaluating Shapley additive explanation contribution plots, feature importance was studied. Of the 130,979 patients studied, 36,042 (27.5%) were female, and the mean (SD) age was 58.2 (13.7) years. The Gradient Boosting Machine model performed the best, achieving 81.8% accuracy and 97.7% precision for 5-year prediction. Moreover, 10-year predictions demonstrated 80.0% accuracy and 94.0% precision. The number of prior tumors, patient age, the site of cancer recurrence, and tumor histology were the most significant predictors. The implementation of our novel SEER framework enabled the successful identification of patients with OTSCC recurrence, with which highly accurate and sensitive prediction models were generated. Thus, we demonstrate our framework's potential for application in various cancers to build generalizable screening tools to predict tumor recurrence.