Tongue Squamous Cell Carcinoma Patients Research Articles

LncRNA CCAT1 knockdown suppresses tongue squamous cell carcinoma progression by inhibiting the ubiquitination of PHLPP2.

Tongue squamous cell carcinoma (TSCC) is prevailing malignancy in the oral and maxillofacial region, characterized by its high frequency. LncRNA CCAT1 can promote tumorigenesis and progression in many cancers. Here, we investigated the regulatory mechanism by which CCAT1 influences growth and metastasis of TSCC. Levels of CCAT1, WTAP, TRIM46, PHLPP2, AKT, p-AKT, and Ki67 in TSCC tissues and cells were assessed utilizing qRT-PCR, Western blot and IHC. Cell proliferation, migration, and invasion were evaluated utilizing CCK8, colony formation, wound healing and transwell assays. Subcellular localization of CCAT1 was detected utilizing FISH assay. m6A level of CCAT1 was assessed using MeRIP. RNA immunoprecipitation (RIP), Co-immunoprecipitation (Co-IP) and RNA pull down elucidated binding relationship between molecules. Nude mouse tumorigenesis experiments were used to verify the TSCC regulatory function of CCAT1 in vivo. Metastatic pulmonary nodules were observed utilizing hematoxylin and eosin (HE) staining. CCAT1 silencing repressed TSCC cell proliferation, migration and invasion. Expression of CCAT1 was enhanced through N6-methyladenosine (m6A) modification of its RNA, facilitated by WTAP. Moreover, IGF2BP1 up-regulated CCAT1 expression by stabilizing its RNA transcript. CCAT1 bond to PHLPP2, inducing its ubiquitination and activating AKT signaling. CCAT1 mediated the ubiquitination and degradation of PHLPP2 by TRIM46, thereby promoting TSCC growth and metastasis. CCAT1/TRIM46/PHLPP2 axis regulated proliferation and invasion of TSCC cells, implying that CCAT1 would be a novel therapeutic target for TSCC patients.

MicroRNA expression as a prognostic biomarker of tongue squamous cell carcinoma (TSCC): a systematic review and meta-analysis

BackgroundRecent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research.MethodsA comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger’s rank correlation test and sensitivity analysis.ResultsEleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25–1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis.ConclusionMiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC.

Depth of invasion as an independent prognostic factor in early-stage oral cavity squamous cell carcinoma

PurposeTo determine the significance of depth of invasion as a predictor of recurrence and mortality in tongue and non-tongue early-stage oral cavity squamous cell carcinoma patients treated with surgery and no postoperative radiotherapy. Materials and methods344 patients with oral cavity squamous cell carcinoma from 2005 to 2022 at a tertiary academic medical center were reviewed. Patients were included if they had newly diagnosed, previously untreated T1-T2N0 disease treated with surgery alone that was observed within a follow-up of 5 years. For each patient, anatomic site of oral cavity squamous cell carcinoma was categorized as either tongue or non-tongue. Cox proportional hazards regression analyses were performed to determine the association of depth of invasion with recurrence and mortality, with anatomic site, smoking status, and age at biopsy as covariates. Model assumptions were tested by statistical and graphical evaluation using Schoenfeld residuals. ResultsOf 108 patients with T1-T2N0 disease, 78 (72.2 %) had tongue disease, and 30 (27.8 %) had non-tongue disease. Median follow-up was 18.2 months (range, 0.01–58.2 months). In the Cox proportional hazards models, with adjustment for anatomic site and other covariates, depth of invasion positively predicted recurrence (HR 1.16, 95 % CI: 1.01–1.32, p = 0.034) and death (HR 1.42, 95 % CI: 1.11–1.83, p = 0.006). ConclusionsDepth of invasion is an independent predictor of recurrence and death across early-stage tongue and non-tongue squamous cell carcinoma. Therefore, depth of invasion may indicate a need for more aggressive treatment than surgery alone, such as postoperative radiotherapy, even in the absence of other adverse features on pathology within the early-stage population.

Influence of Social Vulnerability in Treatment and Prognosis of Squamous Cell Carcinoma of the Tongue.

To investigate the association of social determinants of health (SDoH) in squamous cell carcinoma of the tongue in the United States and to evaluate the real-world contribution of specific disparities. Retrospective cohort study. United States. The Centers for Disease Control and Prevention-Social Vulnerability Index (SVI) and National Cancer Institute-Surveillance, Epidemiology, and End Results Programdatabase were used to study 62,103 adult tongue squamous cell carcinoma patients from 1975 to 2017. Regression analysis assessed trends in months of follow-up and survival across social vulnerability and 4 subcategories of social vulnerability. As overall SVI score increases (increased social vulnerability), there is a significant decrease in the average length of follow-up (22.95% decrease from 63.99 to 49.31 months; P < .001) across patients from the lowest and highest social vulnerability groups. As overall SVI score increases, there is a significant decrease in the average months of survival (28.00% decrease from 49.20 to 35.43 months; P < .001). There is also a significantly greater odds ratio (OR = 1.05; P < .001) of advanced cancer staging upon presentation at higher SVI scores. Patients with higher SVI scores have a lower OR (0.93; P < .001) of receiving surgery as their primary treatment when compared to patients with lower SVI scores. Patients with higher SVI scores also have a significantly greater OR (OR = 1.05; P < .001) of receiving chemotherapy as their primary treatment when compared to patients with lower SVI scores. Increased social vulnerability is shown to have a detrimental impact on the treatment and prognosis of patients with squamous cell carcinoma of the tongue.

Novel Prognostic Model Construction of Tongue Squamous Cell Carcinoma Based on Apigenin-Associated Genes.

Clinical indexes are often selected as relevant factors for constructing prognostic models of tongue squamous cell carcinoma (TSCC) patients, while factors related to therapeutic targets are less frequently included. As Apigenin (API) shows anti-tumor properties in many tumors, in this study, we construct a novel prognostic model for TSCC patients based on Apigenin-associated genes through transcriptomic analysis. The effect of Apigenin (API) on the cell characteristics of TSCC cells was measured by several phenotype experiments. RNA-seq was executed to ensure differentially expressed genes (DEGs) in squamous cell carcinoma-9 (SCC-9) cells after API treatment. Furthermore, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to verify the expression of API-related genes. Then, combined with the gene expression data and relevant individual information of TSCC samples acquired from The Cancer Genome Atlas (TCGA), an API-related model was built through Lasso regression and multivariate Cox regression. A receiver operating characteristic (ROC) curve and a nomogram and calibration curve were created to forecast patient outcomes to improve the clinical suitability of the API-related signature. The relationships between the two risk groups and function enrichment, immune infiltration characteristics, and drug susceptibility were analyzed. We demonstrated that API could inhibit the malignant behavior of TSCC cells. Among API-related genes, TSCC cells treated with API, compared to the control group, have higher levels of transmembrane protein 213 (TMEM213) and G protein-coupled receptor 158 (GPR158), and lower levels of caspase 14 (CASP14) and integrin subunit alpha 5 (ITGA5). An 7 API-associated gene model was built through Lasso regression and multivariate Cox regression that could direct TSCC prognostic status and tumor immune cell infiltration. In addition, we acquired 6 potential therapeutic agents for TSCC based on the prognostic model. Our research suggested the inhibition effect of API on TSCC cells and provided a novel prognostic model combined with therapeutic factors that can guide the prognosis of TSCC and clinical decision-making in TSCC.

HHLA2 is more significantly associated with poor prognosis in TSCC than PD-L1.

The incidence and mortality of tongue squamous cell carcinoma have shown an alarming increase in recent years. This study aimed to investigate the potential of HHLA2 as an immune checkpoint in comparison to PD-L1. We obtained RNA-seq data from TCGA to study HHLA2 and PD-L1 expression across various tissues. Using the CIBERSORT package, we estimated cell type abundances within mixed populations based on gene expression profiles. Immunohistochemistry was performed to analyze HHLA2 and PD-L1 expression in Tongue squamous cell carcinoma. Prognostic evaluation was carried out with Kaplan-Meier curves and the log-rank test. To explore factors affecting HHLA2, univariate and multivariate Cox regression analyses were conducted with the COX regression model. Additionally, we used single-cell RNA sequencing data from the GEO database for gene set enrichment analysis with genes strongly correlated with HHLA2. Our analysis of RNA-seq data unveiled a significant upregulation of HHLA2 and PD-L1 expression in primary tumors when compared with normal tissue. HHLA2 exhibited a positive expression rate of 36.9%, while PD-L1 had a positive expression rate of 24.6%. HHLA2 emerged as a noteworthy independent risk factor impacting the overall survival of Tongue squamous cell carcinoma patients. The analysis of scRNA-seq data shed light on the involvement of HHLA2 in key pathways related to cell cycle regulation and interferon alpha/beta signaling. This study suggests that in the context of Tongue squamous cell carcinoma, HHLA2 may represent a more promising target for immunotherapy when compared with PD-L1.

Tertiary lymphoid structures in tongue cancer: Association with clinicopathological parameters, preoperative S-1 chemotherapy response, and prognosis.

Tertiary lymphoid structures (TLSs) are observed in cancer-invasive sites of various organs, and show evidence of tumor-specific B and/or T cells, suggesting an active humoral antitumor response. The aim of this study was to evaluate the relationship between TLSs and prognosis in patients with tongue squamous cell carcinoma (TSCC) after preoperative S-1 chemotherapy. Among 196 TSCC cases, 111 patients who received preoperative S-1 chemotherapy were compared to 85 patients who did not receive chemotherapy. We investigated the incidence of TLSs in both preoperative biopsy and resected specimens. TLSs were present in 24 (12%) biopsy specimens and 31 (16%) resected specimens. TLSs were associated with clinicopathologically advanced cases and positivity for lymphatic invasion. None of the cases with pStage 0 (i.e., noninvasive cancer) showed TLSs. In preoperative S-1 chemotherapy cases, TLSs were significantly more common in those treated with S-1 for more than 21 days and in those with treatment effects 0, Ia, and Ib. TLSs may not be a favorable prognostic factor by themselves but maybe a prognostic factor when combined with preoperative S-1 treatment. The presence of TLSs was suggested to be a factor indicating a favorable prognosis when considering the indication for preoperative S-1 chemotherapy. The synergistic effect of S-1 by activating antitumor immunity may be associated with a better prognosis in TSCC patients with TLSs.

PDGF-BB accelerates TSCC via fibroblast lactates limiting miR-26a-5p and boosting mitophagy

The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.

Expression of interleukin-34 in tongue squamous cell carcinoma and its clinical implications

To investigate the expression of interleukin- 34 (IL-34) in tongue squamous cell carcinoma (TSCC) and its clinical implications. Serum IL-34 level was detected in 36 patients with TSCC and 36 healthy individuals using enzymelinked immunosorbent assay (ELISA). The expressions of IL-34 mRNA and protein levels in TSCC and adjacent tissues were examined in 41 patients using real-time fluorescence quantitative PCR (qRT-PCR) and immunohistochemistry (IHC), and their correlation with the clinicopathological features of the patients was further analyzed. Informatic analysis of the differentially expressed genes related with IL-34 in TSCC was carried out based on String database, LinkedOmics database and GEO database, and GO functional analysis and KEGG signaling pathway enrichment analysis were performed using Webgestalt database. The serum level of IL-34 was significantly lower in TSCC patients than in the healthy individuals (P < 0.001), and its expression level was also significantly lower in the tumor tissues than in the adjacent tissues (P < 0.001). The expression level of IL-34 in TSCC tissues was related with lymph node metastasis and TNM staging (P < 0.05), but not with age, gender, smoking, drinking, or tumor size (P > 0.05). Informatic analysis suggested that IL-34 had the strongest correlation with CSF1R and PTPRJ. IL-34 and its related genes in TSCC were enriched mainly in bone marrow cell differentiation, collagen-containing extracellular matrix, and cytokine binding and signal receptor activator activity. KEGG signaling pathway enrichment showed that IL-34 and the related differentially expressed genes were involved mainly in osteoclast differentiation, protein polysaccharide in cancer, and the MAPK signaling pathway. IL-34 is lowly expressed in TSCC and participates in the occurrence and progression of TSCC, and can be potentially used as a new diagnostic biomarker and therapeutic target for TSCC.

The application of radiomics machine learning models based on multimodal MRI with different sequence combinations in predicting cervical lymph node metastasis in oral tongue squamous cell carcinoma patients.

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. 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. 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). The radiomics machine learning models based on CE-MRI showed great accuracy and stability in predicting the risk of CLNM for OTSCC patients.

Evaluation of the Local Control Rate and Late Toxicity of High-Dose-Rate Interstitial Brachytherapy in Tongue Squamous Cell Carcinoma

Background: Tongue Squamous Cell Carcinoma (TSCC) is one of the most consequential oral Squamous Cell Carcinomas (SCC) worldwide.&#x0D; Methods: This retrospective cross-sectional study was conducted on 29 TSCC patients treated with High Dose Rate Brachytherapy (HDR-BT) with or without External Beam Radiotherapy (EBRT) between 2017-2020. Patients without distant metastasis at the time of treatment and at least one year after completion of brachytherapy were included.&#x0D; Results: One-year Overall Survival (OS), Disease-Free Survival (DFS), and Local Control Rate (LCR) were 82.8, 79.3, and 100%, respectively. 6 patients (20.7%) had distant metastasis, of which 5 (17.2%) died. Local recurrence was not observed in any patients, and only one (3.4%) regional recurrence occurred. The most common late toxicity of HDR-BT was dry mouth (79.2%) and dysarthria (66.7%). There were no severe and life-threatening complications (grades 3 and 4) during one year. Also, 79.2% of the patients had good functional performance. One-year OS, the significant difference between the two groups of HDR-BT with and without EBRT (p=0.055).&#x0D; Conclusion: Our findings indicated that the HDR-BT increases the OS of TSCC patients more than EBRT without developing grade 3-4 AEs and metastasis. We showed that the mean 3.2 ±0.7 Gy of HDR-BT has more OS compared to EBRT.

Construction and validation of a prognostic model for tongue cancer based on three genes signature.

Tongue squamous cell carcinoma (TSCC) has a poor prognosis and destructive characteristics. Reliable biomarkers are urgently required to predict disease outcomes and to guide TSCC treatment. This study aimed to develop a multigene signature and prognostic nomogram that can accurately predict the prognosis of patients with TSCC. We screened differentially expressed genes associated with TSCC using The Cancer Genome Atlas dataset. Based on this, we developed a new multi-mRNA gene signature using univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression, and multivariate Cox regression. We used the concordance index to evaluate the accuracy of this new multigene model. Moreover, we performed receiver operating characteristic and Kaplan-Meier survival analyses to assess the predictive ability of the new multigene model. In addition, we created a prognostic nomogram incorporating clinical and pathological characteristics, with the aim of enhancing the adaptability of this model in practical clinical settings. We successfully developed a new prognostic model based on the expression levels of these 3 mRNAs that can be used to predict the prognosis of patients with TSCC. This prediction model includes 3 genes: KRT33B, CDKN2A, and CA9. In the validation set, the concordance index of this model was 0.851, and the area under the curve was 0.778 and 0.821 in the training and validation sets, respectively. Kaplan-Meier survival analysis showed that regardless of whether it was in the training or validation set, the prognosis of high-risk patients was significantly worse than that of low-risk patients (P < .001). Multivariate Cox regression analysis revealed that this model was an independent prognostic factor for patients with TSCC (P < .001). Our study suggests that this 3-gene signature model has a high level of accuracy and predictive ability, is closely related to the overall survival rate of patients with TSCC, and can independently predict the prognosis of TSCC patients with high accuracy and predictive ability.

Occult Lymph Node Metastasis in cN0 Tongue Squamous Cell Carcinoma: A Prospective Observational Study

Tongue squamous cell carcinoma (TSCC) is prone to occult lymph node metastasis, and preoperative evaluation of cervical nodes is critical for determining treatment strategies. There is scarce report of detecting occult lymph node metastasis in TSCC by using multi-parameter magnetic resonance imaging (mpMRI), spectral computed tomography (spectral CT) or other diagnostic functional imaging. In this study, we aimed to analyze the incidence and risk factors of occult lymph node metastasis in cN0 TSCC by comparing preoperative imaging with postoperative pathology results. This study prospectively enrolled newly-diagnosed cN0 TSCC patients admitted to the Hunan Cancer Hospital between May, 2022 and December, 2022. All patients underwent primary resection and selective dissection of cervical lymph nodes. MpMRI and spectral CT scan of oral cavity and neck were performed prior to surgery. Preoperative evaluation of lymph node metastasis was conducted by two senior radiologists independently. The location of cervical lymph nodes was assigned based on the 2013 consensus guidelines. A total of 26 cN0 TSCC patients (6 cT1 stage, 13 cT2 stage, and 7 cT3 stage) were enrolled. The median age was 53 (range, 36-64), and there were 25 males. Among all patients, 13 patients underwent unilateral cervical lymph node dissection, while 13 patients underwent bilateral cervical lymph node dissection. A total of 208 lymphatic drainage areas were resected, and 1003 lymph nodes were removed. There were 7 of pT1, 12 of pT2, 7 of pT3 based on postoperative pathological stages. Besides, there are 21 cases staged pN0, 2 cases staged pN1, 2 cases staged pN2, and 1 case staged pN3. Among the 26 patients, 5 (19.23%) cases had occult lymph node metastasis. A total of 8 metastatic lymph nodes (4 in ipsilateral Ib level, 1 in contralateral Ib level, 3 in IIa level ipsilateral side) were detected in the whole group. No lymph node metastasis was detected in level IIb, III and IV. The median maximum diameter of metastatic lymph nodes was 12 mm (range 5 to 15 mm), and 1 extra-nodal extension was observed. Moreover, all occult lymph node metastases occurred in patients with a primary invasion depth of ≥ 5 mm (29.41%, 5/17). The incidence of occult lymph node metastasis in cN0 TSCC remains high under functional imaging diagnostic technology. Preventive neck dissection is necessary for patients with cN0 disease, especially those with primary tumor invasion depth exceeding 5 mm.

HALP score based on hemoglobin, albumin, lymphocyte and platelet can predict the prognosis of tongue squamous cell carcinoma patients

ObjectiveThe preoperative hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a comprehensive marker of nutritional and immunological status, has been found to be robust for tumor prognosis prediction. Here, we evaluated the use of HALP in the prognostic prediction of tongue squamous cell carcinoma (TSCC). Study designPatients with TSCC were retrospectively recruited from the years 2009–2019. Patient clinicopathological characteristics, along with preoperative blood parameters, were recorded on admission, and the cut-off HALP value was determined by X-tile software. Kaplan-Meier curves and Cox regression analyses were used to evaluate the predictive value of HALP for patient overall survival (OS) and disease-free survival (DFS). ResultsA total of 339 TSCC patients were enrolled. The optimal HALP threshold was 56 and the patients were divided into two groups according to their scores. The Kaplan-Meier analysis showed that patients in the high-HALP group experienced longer OS (p = 0.007) and DFS (p = 0.006) than those in the low-HALP group. Multivariate analysis showed that elevated HALP (p = 0.038) was an independent predictor of OS, while age (p = 0.008), T stage (p < 0.001), N stage (p = 0.020), and degree of tumor differentiation (p < 0.001) were risk factors. ConclusionThe findings showed that the preoperative HALP score was an independent predictor of prognosis in patients with TSCC.

Single Lymph Node Metastasis and Adjuvant Therapy in Stage III Tongue Cancer

Background and Objectives We analyzed treatment results among stage III oral tongue squamous cell carcinoma (OTSCC) patients and performed subgroup analyses according to the depth of invasion (DOI) and node positivity.Subjects and Method We retrospectively analyzed the medical records of 87 stage III OTSCC patients.Results A total of 32 recurrences occurred during the study period, eight cases of local recurrence, 12 cases of regional recurrence, eight cases of distant metastasis, and four cases of loco-regional recurrence. During the study period, 27 patients died due to disease progression. The 5-year recurrence-free survival of the patients was 62.9%, and the 5-year disease-specific survival (DSS) was 75.3%. When prognostic factors related to disease recurrence and survival were analyzed through univariate and multivariate analyses, only the N classification was significantly associated with patient survival (hazard ratio 0.36, confidence interval 0.14-0.91). The 5-year DSS of N0 patients was 87.6%, and the 5-year DSS of N1 patients was 63.9%. Among N1 patients, the 5-year DSS was 90.5% when adjuvant therapy was administered and 63.9% when adjuvant therapy was not administered, which is a statistically significant difference. We did not observe any difference in treatment outcome or survival between patients with superficial (DOI ≤10 mm) or deep lesions (DOI &gt;10 mm).Conclusion Among the stage III OTSCC patients, patients with single lymph node (LN) metastasis (N1) showed a distinct prognostic difference from other patients (N0), and the administration of adjuvant therapy to patients having single LN metastasis without other risk factors significantly improved their 5-year DSS.

Oral Potentially Malignant Disorders and Candida in Oral Tongue Squamous Cell Carcinoma Patients.

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.

IMMUNE MICROENVIRONMENT AND PROGNOSIS OF TONGUE SQUAMOUS CELL CARCINOMAS

Objective To characterize immune cells in the tumor microenvironment of Tongue Squamous Cell Carcinoma (TSCC) and to evaluate its prognostic significance. Study Design forty-eight cases of TSCC were selected. Immunohistochemical reactions were carried out against CD3, CD4, CD8, CD20, CD68, CD1a, CD83, PD-1, and PD-L1; the analysis was performed to investigate the relation between the type of immune cells and clinical characteristics, such as tumor size, presence of local and distant metastasis, and overall survival. Results Analysis revealed that high expression CD3, CD8, CD20, and CD83 were statistically significant when associated with an improvement in overall survival rate. Conclusion Evidence to support the values higher of tumor-infiltrating lymphocytes (TILs) and mature dendritic cells (DC) are correlated with improvements in overall survival in TSCC patients, influenced by characteristics and behaviors of tumor and prognosis. To characterize immune cells in the tumor microenvironment of Tongue Squamous Cell Carcinoma (TSCC) and to evaluate its prognostic significance. forty-eight cases of TSCC were selected. Immunohistochemical reactions were carried out against CD3, CD4, CD8, CD20, CD68, CD1a, CD83, PD-1, and PD-L1; the analysis was performed to investigate the relation between the type of immune cells and clinical characteristics, such as tumor size, presence of local and distant metastasis, and overall survival. Analysis revealed that high expression CD3, CD8, CD20, and CD83 were statistically significant when associated with an improvement in overall survival rate. Evidence to support the values higher of tumor-infiltrating lymphocytes (TILs) and mature dendritic cells (DC) are correlated with improvements in overall survival in TSCC patients, influenced by characteristics and behaviors of tumor and prognosis.

Occult lymph node metastasis in cN0 tongue squamous cell carcinoma: A prospective observational study.

e18066 Background: Tongue squamous cell carcinoma (TSCC) is prone to occult lymph node metastasis, and preoperative evaluation of cervical nodes is critical for determining treatment strategies. There is scarce report of detecting occult lymph node metastasis in TSCC by using multi-parameter magnetic resonance imaging (mpMRI), spectral computed tomography (spectral CT) or other diagnostic functional imaging. In this study, we aimed to analyze the incidence and risk factors of occult lymph node metastasis in cN0 TSCC by comparing preoperative imaging with postoperative pathology results. Methods: This study prospectively enrolled newly-diagnosed cN0 TSCC patients admitted to the Hunan Cancer Hospital between May, 2022 and December, 2022. All patients underwent primary resection and selective dissection of cervical lymph nodes. MpMRI and spectral CT scan of oral cavity and neck were performed prior to surgery. Preoperative evaluation of lymph node metastasis was conducted by two senior radiologist independently. The location of cervical lymph nodes was assigned based on the 2013 consensus guidelines. Results: A total of 26 cN0 TSCC patients (6 cT1 stage, 13 cT2 stage, and 7 cT3 stage) were enrolled. The median age was 53 (range, 36-64), and there were 25 males. Among all patients, 13 patients underwent unilateral cervical lymph node dissection, while 13 patients underwent bilateral cervical lymph node dissection. A total of 208 lymphatic drainage areas were resected, and 1003 lymph nodes were removed. There were 7 of pT1, 12 of pT2, 7 of pT3 based on postoperative pathological stages. Besides, there are 21 cases staged pN0, 2 cases staged pN1, 2 cases staged pN2, and 1 case staged pN3. Among the 26 patients, 5 (19.23%) cases had occult lymph node metastasis. A total of 8 metastatic lymph nodes (4 in ipsilateral Ib level, 1 in contralateral Ib level, 3 in IIa level ipsilateral side) were detected in the whole group. No lymph node metastasis was detected in level IIb, III and IV. The median maximum diameter of metastatic lymph nodes was 12 mm (range 5 to 15 mm), and 1 extra-nodal extension was observed. Moreover, all occult lymph node metastases occurred in patients with a primary invasion depth of ≥ 5 mm (29.41%, 5/17). Conclusions: The incidence of occult lymph node metastasis in cN0 TSCC remains high under functional imaging diagnostic technology. Preventive neck dissection is necessary for patients with cN0 disease, especially those with primary tumor invasion depth exceeding 5 mm.

Expression and effect of heterogeneous nuclear ribonucleoprotein A2/B1 in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is a common cancer in the oral and maxillofacial region, which seriously endangers people's life and health.Heterogeneous nuclear ribonucleoprotein A2/B1(hnRNP A2/B1) is an RNA-binding protein that regulates the expression of a variety of genes and participates in the occurrence and development of a variety of cancers. This study aims to investigate the role of hnRNP A2/B1 in TSCC progression. The differential expression of hnRNP A2/B1 in oral squamous cell carcinoma (OSCC) and normal oral mucosa cells and tissues was analyzed based on the gene expression profiles of GSE146483 and GSE85195 in the Gene Expression Omnibus (GEO) database. The correlation between hnRNP A2/B1 expression and disease-free survival of TSCC patients was analyzed based on TSCC related chip of GSE4676. TSCC cancer and paracancerous tissue samples of 30 patients were collected in Hunan Cancer Hospital from July to December 2021. Real-time RT-PCR and Western blotting were used to verify the mRNA and protein expression of hnRNP A2/B1 in TSCC patients'samples, respectively. Human TSCC Tca-8113 cells were transfected with hnRNP A2/B1 empty vector (a sh-NC group), knockdown plasmid (a sh-hnRNP A2/B1 group), empty vector overexpression plasmid (an OE-NC group) and overexpression plasmid (an OE-hnRNP A2/B1 group), respectively. The knockdown or overexpression efficiency of hnRNP A2/B1 was detected by Western blotting. The proliferation activity of Tca-8113 cells was detected by cell counting kit-8 (CCK-8), and the apoptosis rate of Tca-8113 cells was detected by flow cytometry. Based on the analysis of OSCC-related chips of GSE146483 and GSE85195 in the GEO database, it was found that hnRNP A2/B1 was differentially expressed in the OSCC and normal oral mucosa cells and tissues (all P<0.01). Meanwhile, the analysis of TSCC related chip GSE4676 confirmed that the expression of hnRNP A2/B1 was negatively correlated with the disease-free survival of TSCC patients (P=0.006). The results of real-time RT-PCR and Western blotting showed that the relative expression levels of hnRNP A2/B1 mRNA and protein in TSCC tissues were significantly up-regulated compared with those in adjacent tissues (all P<0.01). The results of Western blotting showed that the expression level of hnRNP A2/B1 in Tca-8113 cells was significantly inhibited or promoted after knockdown or overexpression of hnRNP A2/B1 (all P<0.01). The results of CCK-8 and flow cytometry showed that inhibition of hnRNP A2/B1 expression in Tca-8113 cells reduced cell proliferation activity (P<0.05) and increased cell apoptic rate (P<0.01). Overexpression of hnRNP A2/B1 in Tca-8113 cells significantly increased cell proliferation (P<0.05) and decreased cell apoptosis (P<0.01). HnRNP A2/B1 is a key factor regulating the proliferation and apoptosis of TSCC cells. Inhibition of hnRNP A2/B1 expression can reduce the proliferation activity of TSCC cells and promote the apoptosis of TSCC cells.

Mena as a key enhancer factor of EMT to promote metastasis of human tongue squamous cell carcinoma.

The aim of this study was to investigate the effect of mammalian-enabled (Mena) on tongue squamous cell carcinoma (TSCC) metastasis and its mechanism. Immunochemistry was performed to investigate the Mena and tumor-related markers expression, and its clinicopathological characteristics in 46 TSCC specimens. TSCC cell SCC9 and Cal27 untransfected or stable transfected with Mena overexpression and small interfering RNA were used to determine the role of Mena in cell proliferation, cell migration, invasion and metastasis, and EMT-related markers in vitro, and the effect of Mena on TSCC growth and metastasis through tumor-bearing and tumor metastasis immunodeficient mice models in vivo. Immunochemistry showed that the expression of Mena was significantly correlated with lymphatic metastasis and TNM stage, E-cadherin, Vimentin, and MMP2. Mena did not affect cell proliferation and colony formation in vitro, and tumor growth in vivo. However, it promoted cell migration and invasion in vitro, and TSCC metastasis in vivo. Mena expression is associated with lymphatic metastasis and tumor stage and promotes TSCC invasion and metastasis by inducing the EMT process. Thus, Mena may be a biomarker for prognosis and targeted therapy in TSCC patients.