Prognosis Of Oral Squamous Cell Carcinoma Research Articles

LncRNA FOXD2-AS1 promotes the growth, invasion and migration of OSCC cells by regulating the MiR-185–5p/PLOD1/Akt/mTOR pathway

Although lncRNAs are recognized to contribute to the development of oral squamous-cell carcinoma (OSCC), their exact function in invasion and cell migration is not clear. In this research, we explored the molecular and cellular mechanisms of FOXD2-AS1 in OSCC. Prognostic and bioinformatics analyses were used to test for the differential expression of FOXD2-AS1-PLOD1. Following FOXD2-AS1 suppression or overexpression, changes in cell viability were measured using the CCK-8 test; changes in cell migration and invasion abilities were measured using the migration and the Transwell assay. The expression of associated genes and proteins was found using Western blot and RT-qPCR. Analysis of luciferase reporter genes was done to look for regulatory connections between various molecules. The FOXD2-AS1-PLOD1 pair, which was highly expressed in OSCC, was analyzed and experimentally verified to be closely related to the prognosis of OSCC, and a nomogram model and correction curve were constructed. The inhibition of FOXD2-AS1 resulted in the reduction of cell activity, migration, invasion ability and changes in genes related to invasion and migration. In vivo validation showed that inhibition of FOXD2-AS1 expression slowed tumor growth, and related proteins changed accordingly. The experiments verified that FOXD2-AS1 negatively regulated miR-185–5 p and that miR-185–5 p negatively regulated PLOD1. In addition, it was found that the expression of PLOD1, p-Akt and p-mTOR proteins in OSCC cells was reduced by the inhibition of FOXD2-AS1, and FOXD2-AS1 and PLOD1 were closely related to the Akt/mTOR pathway. Increased expression of FOXD2-AS1 promotes OSCC growth, invasion and migration, which is important in part by targeting miR-185–5 p/PLOD1/Akt/mTOR pathway activity.

Neutrophil extracellular traps promote invasion and metastasis via NLRP3-mediated oral squamous cell carcinoma pyroptosis inhibition

Neutrophil extracellular traps (NETs) are reticular structures composed of neutrophil elastase (NE), cathepsin G (CG) and DNA-histone enzyme complexes. Accumulating evidence has revealed that NETs play important roles in tumor progression, metastasis, and thrombosis. However, our understanding of its clinical value and mechanism of action in oral squamous cell carcinoma (OSCC) is limited and has not yet been systematically described. Here, we aimed to investigate the clinical significance of NETs in OSCC and the mechanisms by which they affect its invasive and metastatic capacity. Our results demonstrated that high enrichment of NETs is associated with poor prognosis in OSCC, and mechanistic studies have shown that NE in NETs promotes invasion and metastasis via NLRP3-mediated inhibition of pyroptosis in OSCC. These findings may provide a new therapeutic approach for OSCC.

Underlying bone change in oral squamous cell carcinoma observed from magnetic resonance imaging and computed tomography: Potential implications for tumor aggressiveness and prognosis

Background/purposeIn cases where oral squamous cell carcinoma (OSCC) invades the jawbone, clinicians frequently observe abnormal attenuation on computed tomography (CT) and pathologic signal intensity (SI) on magnetic resonance (MR) imaging of the affected underlying bone marrow. This study introduced a concept of “underlying bone change” to examine its association with clinicopathological features and prognosis of OSCC, as well as its correlation with medullary invasion. Materials and methodsWe enrolled 93 consecutive patients diagnosed with OSCC, who underwent mandibulectomy between 2010 and 2016. CT and MR images, along with electronic medical records, were reviewed to evaluate correlations between underlying bone changes, clinicopathological features, five-year overall survival, and medullary invasion. ResultsOf the 93 patients, 69 (74.2%) exhibited underlying bone sclerosis on CT, and 74 (79.6%) displayed pathological SI on MR images. These underlying bone changes correlated with the T stage and recurrence, but not with overall survival.Medullary invasion, observed in 61 (65.6%) patients, was strongly associated with T and TNM stages and was linked to poorer overall survival.The underlying bone changes on CT and MR images were positively associated with medullary invasion; however, no significant differences were found in the occurrence of underlying bone changes between the subtypes based on the extent of medullary invasion. ConclusionUnderlying bone changes on CT and MR images can provide valuable insights into the aggressiveness of bone invasion by OSCC. Accurate interpretation of these imaging findings might be crucial for correctly delineating surgical margins and preventing the overestimation of tumor extent.

LncRNA FOXD2-AS1 Promotes the Growth, Invasion and Migration of OSCC Cells by Regulating the MiR-185-5p/PLOD1/Akt/mTOR Pathway

Although lncRNAs are recognized to contribute to the development of oral squamous-cell carcinoma (OSCC), their exact function in invasion and cell migration is not clear. In this research, we explored the molecular and cellular mechanisms of FOXD2-AS1 in OSCC. Prognostic and bioinformatics analyses were used to test for the differential expression of FOXD2-AS1-PLOD1. Following FOXD2-AS1 suppression or overexpression, changes in cell viability were measured using the CCK-8 test; changes in cell migration and invasion abilities were measured using the migration and the Transwell assay. The expression of associated genes and proteins was found using Western blot and RT-qPCR. Analysis of luciferase reporter genes was done to look for regulatory connections between various molecules. The FOXD2-AS1-PLOD1 pair, which was highly expressed in OSCC, was analyzed and experimentally verified to be closely related to the prognosis of OSCC, and a nomogram model and correction curve were constructed. The inhibition of FOXD2-AS1 resulted in the reduction of cell activity, migration, invasion ability and changes in genes related to invasion and migration. In vivo validation showed that inhibition of FOXD2-AS1 expression slowed tumor growth, and related proteins changed accordingly. The experiments verified that FOXD2-AS1 negatively regulated miR-185-5p and that miR-185-5p negatively regulated PLOD1. In addition, it was found that the expression of PLOD1, p-Akt and p-mTOR proteins in OSCC cells was reduced by the inhibition of FOXD2-AS1, and FOXD2-AS1 and PLOD1 were closely related to the Akt/mTOR pathway. Increased expression of FOXD2-AS1 promotes OSCC growth, invasion and migration, which is important in part by targeting miR-185-5p/PLOD1/Akt/mTOR pathway activity.

Association of DOK3 and infiltrated tumor-associated macrophages with risk for the prognosis of Porphyromonas gingivalis-infected oral cancer: a 12-year data analysis of 200 patients from a tertiary teaching hospital, Urumqi, China

BackgroundWhile there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients’ prognosis.MethodsA prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher’s exact test or Pearson’s chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan–Meier approach and log-rank test were used to plot the survival curves.ResultsThe expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P < 0.001). Parameters, including body mass index, clinical stage, recurrence, tumor differentiation, and P. gingivalis, DOK3, and M2-TAM immunoexpression levels, affected the prognosis of patients with OSCC (all P < 0.05). In addition, P. gingivalis (HR = 1.674, 95%CI 1.216–4.142, P = 0.012), DOK3 (HR = 1.881, 95%CI 1.433–3.457, P = 0.042), and M2-TAM (HR = 1.649, 95%CI 0.824–3.082, P = 0.034) were significantly associated with the 10-year cumulative survival rate.ConclusionsElevated expression of P. gingivalis and DOK3 indicates M2-TAM infiltration and unfavorable prognosis of OSCC, and could be considered as three novel independent risk factors for predicting the prognosis of OSCC.

High expression of ACTL6A leads to poor prognosis of oral squamous cell carcinoma patients through promoting malignant progression.

The aim was to research ACTL6A's role in oral squamous cell carcinoma (OSCC). OSCC and normal samples were obtained from patients and public databases. GSEA was performed. CIBERSORT was utilized to analyze immune landscape. Kaplan-Meier survival analysis and multivariate Cox regression analysis were conducted. After knocking down ACTL6A, we performed MTT assay, transwell assays, and flow cytometry to detect the impact of knockdown. ACTL6A expressed higher in OSCC samples than normal samples. The CNV and mutation rate of TP53 was higher in ACTL6A high-expression group. TFs E2F7 and TP63 and miRNA hsa-mir-381 were significantly related to ACTL6A. ACTL6A could influence immune microenvironment of OSCC. Knockdown of ACTL6A inhibited OSCC cells' proliferation, migration, and invasion. ACTL6A was able to predict OSCC prognosis independently. ACTL6A expressed higher in OSCC than normal samples and it could be used as an independent prognostic marker in OSCC patients.

Abstract 6992: Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of oral squamous cell carcinoma

Abstract Background:Oral squamous cell carcinoma (OSCC) stands as a prevalent malignancy worldwide. Profilin 2 (PFN2), an actin-binding protein regulating actin polymerization dynamics and associated with cell motility, has recently gained attention as a significant regulator in various cancers. However, the clinical significance and biological function of PFN2 in OSCC remain debatable. This study aims to elucidate the role of PFN2 in OSCC. Methods:We assessed PFN2 expression in OSCC and adjacent normal oral mucosa tissues through Q-RT-PCR and immunohistochemistry analysis. Associations between PFN2 expression, clinicopathological features, and OSCC prognosis were analyzed. Cell proliferation, invasion, and migration effects were examined via MTT and Transwell assays. Western blotting assessed the protein expression related to epithelial–mesenchymal transition (EMT). Additionally, we established OSCC xenografts to determine tumorigenicity in vivo using female Nude mice. Results:PFN2 RNA and protein expression were significantly increased in OSCC compared to normal oral mucosa. PFN2 expression positively correlated with lymphovascular invasion and cervical lymph node metastasis. MTT and Transwell assays demonstrated that PFN2 promoted OSCC cell proliferation, migration, invasion, and endothelial invasion. Downregulation of PFN2 induced an EMT phenotype, including an increase in the expression of the epithelial marker E-cadherin and a decrease in the expression of mesenchymal markers Vimentin, Snail, and Slug in OSCC cells in vitro. Similarly, OSCC cells with reduced PFN2 expression exhibited weaker tumorigenicity in vivo. Conclusions:Our findings unveil a novel role for PFN2 in promoting OSCC progression and metastasis, suggesting its potential as an early biomarker for high-risk populations. Targeting PFN2 may offer a promising therapeutic strategy for OSCC treatment. Citation Format: Chung Ji LIu, Li-Han Lin, Kuo-Wei Chang, Hui-Wen Cheng. Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6992.

Abstract 2451: Investigation of SIRT6 usefulness as a novel biomarker for oral cancer

Abstract Introduction: SIRT6 is one of the seven human sirtuin genes and is known to function as an onco-suppressor gene in colorectal and ovarian cancers, although it is up-regulated in other cancers. Thus, SIRT6 is considered performing both tumor-suppressing and promoting roles. However, the association of SIRT6 with oral squamous cell carcinoma (OSCC) and its role in OSCC pathogenesis are currently unclear. Currently, SCC or CYFRA are used as a tumor marker to assist in the diagnosis of OSCC in a clinical setting whereas its sensitivity is low. Therefor the development of a novel biomarker for early diagnosis and identification of new therapeutic targets is critical to resolve the pressing clinical issues related to the management of OSCC. This study aimed to investigate the expression and the relevance of SIRT6 in patients with OSCC and its potential as a biomarker for early detection and prognosis prediction. Materials and Methods: This study enrolled 78 patients with OSCC and 9 patients with carcinoma in situ (CIS). The OSCC patients had undergone surgery or chemoradiotherapy (51 surgery and 27 chemoradiotherapy). The CIS patients had undergone surgery. Samples were also obtained from 10 patients with oral potentially malignant disorders (OPMDs). Biopsied or surgical resected samples were used for the study. We obtained 21 noncancerous tissues as normal tissues from the adjacent noncancerous tissues after tumor resection. Immunohistochemistry, quantitative real-time RT-PCR, and microarray analyses were performed to determine SIRT6 expression and its association with clinicopathological features in OSCC, CIS, and OPMDs using clinical paraffin embedded specimens. Results: SIRT6 mRNA levels were higher in OSCC tissues than those in noncancerous tissues (p&amp;lt;0.05). And SIRT6 protein expression levels were higher in OSCC, CIS and OPMDs tissues than those in noncancerous tissues (p&amp;lt;0.05). SIRT6 expression was predominant in patients aged ≥65 years and significantly correlated with shorten overall survival. In the microarray analysis, some SIRT6-associated genes, such as ANXA2 was significantly up-regulated, and PIGC and RGPD4 were down-regulated in OSCC. Conclusion: SIRT6 plays a role in tumor homeostasis, leading to a poor prognosis in OSCC. SIRT6 may represent a novel target not only for the treatment, but also as a prognostic marker in OSCC. Citation Format: Haruka Yoshii, Ami Shimoda, Kenji Mitsudo, Mitomu Kioi. Investigation of SIRT6 usefulness as a novel biomarker for oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2451.

Abstract 5494: Spatial organization between claudin and the tumor microenvironment in head and neck squamous cell carcinomas

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth leading form of cancer worldwide and one of the most difficult and challenging malignancies, with a high level of heterogeneity and a wide range of treatment responses. Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer and accounts for over 90% of cancers that develop within the mucosal epithelium of the oral cavity. Additional carcinogenic risk factors, including tobacco, alcohol and HPV infection are also associated with the pathogenesis of oral carcinogenesis. Unfortunately, today the failure of standard treatment modalities, such as surgery, radiotherapy, and chemotherapy underscore the need to identify better biomarkers of this disease. Advances, especially in spatial technology have created unprecedented opportunities to identify cell types and biomarkers of disease processes, revealing important relationships within the tumor microenvironment (TME) that allow a detailed characterization of specific cell phenotypes defined by co- or lack of expression of multiple markers that may help in predicting clinical responses and mechanisms of resistance to therapy. Recent findings indicate that abnormal expression of claudins (CLDNs) is closely related to the occurrence, progression and prognosis of many solid tumors. Specifically, CLDN6 is expressed in numerous tumors but rarely found in adult normal tissues making it a potential therapeutic target in head and neck tumor types. To investigate this further, expression of CLDN6 and the its relationship with changes within the TME of cohort OSCC tumors was determined using a proprietary comprehensive spatial workflow and gene expression analysis. Methods: A retrospective analysis was performed on biopsied Formalin-Fixed Paraffin-Embedded (FFPE) samples from OSCC patients with and without a history of smoking and treated +/- chemotherapy. Patient samples representing matched normal tissue to serve as controls were compared to samples derived from OSCC tumors. In order to perform a comprehensive expression profiling of the TME from OSCC tumors we used the spatial MultiOmyx™ immunofluorescence (IF) multiplexing assay with transcriptomic information from bulk mRNA gene expression acquired using the NanoString nCounter® PanCancer IO 360™ panel that includes the Tumor Inflammation Signature (TIS), as well as targets that characterize immune hot, desert, and cold regions in the stroma and tumor epithelium. Results: We characterized the expression of CLDN6 across the different cohorts of OSCC samples and further investigated the relationship within the tumor immune microenvironment coupled to genes related to the prognosis of OSCC. A better understanding of the TME and gene expression profiling of OSCC tumors and the effect of smoking will allow us to tailor the treatment of patients to continue to improve outcomes. Citation Format: Kirsteen Maclean, Lakshmi Chandramohan, Maryam Rohafza, Harry Nunns, Erinn Parnell, Qingyan Au, Anna Juncker-Jensen. Spatial organization between claudin and the tumor microenvironment in head and neck squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5494.

Insights into the role of the N6-methyladenosine reader IGF2BP3 in the progression of oral squamous cell carcinoma and its connection to cell-cycle control

The genome of oral squamous cell carcinoma (OSCC) has been extensively characterized via bulk sequencing, revealing a multitude of genetic changes. The gene IGF2BP3, which encodes for the insulin-like growth factor 2 mRNA-binding protein 3, has been observed to be highly expressed in several types of cancer. This finding suggests that IGF2BP3 may play a significant role in the initiation and advancement of cancer. Nevertheless, the mechanisms by which IGF2BP3 contribute to OSCC are yet to be fully understood. In this study, we have observed that IGF2BP3 exhibits overexpression in OSCC. Based on our findings from bulk sequencing analysis, we have concluded that IGF2BP3 could potentially serve as a biomarker for predicting poor prognosis in OSCC. Moreover, it has been demonstrated that IGF2BP3 exhibits a significant association with the initiation and advancement of tumors both in vivo and in vitro. The evaluation of IGF2BP3 expression levels in relation to the cell cycle stage was conducted using single-cell RNA sequencing data. Tumor cells characterized by elevated IGF2BP3 expression demonstrated a higher percentage of cells in the G2/M transition phase. This study presents new findings indicating that the molecular target IGF2BP3 can serve as a prognostic indicator for tumors and has an impact on the development and progression of OSCC by influencing the regulation of the cell cycle.

Prediction of prognosis in oral squamous cell carcinoma using infrared microspectroscopy.

Estimation of prognosis of oral squamous cell carcinoma (OSCC) is inaccurate prior to surgery, only being effected following subsequent pathological analysis of the primary tumour and excised lymph nodes. Consequently, a proportion of patients are overtreated, with an increase in morbidity, or undertreated, with inadequate margins and risk of recurrence. We hypothesise that it is possible to accurately characterise clinical outcomes from infrared spectra arising from diagnostic biopsies. In this first step, we correlate survival with IR spectra derived from the primary tumour. Infrared spectra were collected from tumour tissue from 29 patients with OSCC and subject to classification modelling. The model had a median AUROC of 0.89 with regard to prognosis, a median specificity of 0.83, and a hazard ratio of 6.29 in univariate Cox proportional hazard modelling. The data suggest that FTIR spectra may be a useful early biomarker of prognosis in OSCC.

Association between lymph node ratio and survival outcomes in patients with oral squamous cell carcinoma

Background: Recent reports have shown that the Lymph node ratio (LNR) is useful for predicting the prognosis in some cancers, however there are few reports on the usefulness of LNR in predicting the prognosis of oral squamous cell carcinoma (OSCC). The predictive value of LNR for prognosis of OSCC was investigated. Materials and Methods: The study included 152 patients with OSCC and histologically confirmed cervical lymph node metastasis who underwent neck dissection. We analyzed the relationship between LNR and overall survival (OS) and recurrence-free survival (RFS) retrospectively in these cases, with the relationship between prognosis and clinicopathological findings also examined. Results: Using a receiver operating characteristics curve, the LNR cutoff value was set at 0.095, categorizing 64 and 88 cases into high LNR (≥0.095) and low LNR (<0.095) groups, respectively. Regarding OS and RFS, the prognosis was significantly worse in the high LNR group compared with the low LNR group. In multivariate analysis, sex, postoperative nodal stage, and LNR merged as independent prognostic factors. Conclusion: This study's findings suggest that LNR may represent a prognostic indicator in OSCC with cervical lymph node metastasis.

Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma

BackgroundThe novel form of regulatory cell death, cuproptosis, is characterized by proteotoxicity, which ultimately leads to cell death. Its targeting has emerged as a promising therapeutic approach for oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) participate in epigenetic regulation and have been linked to the progression, prognosis, and treatment of OSCC. Thus, this study aimed to identify new cuproptosis-related lncRNAs (CRLs), establish predictive models for clinical prognosis, immune response, and drug sensitivity, and provide novel insights into immune escape and tumor drug resistance.MethodsThe present study screened eight CRLs (THAP9-AS1, STARD4-AS1, WDFY3-AS2, LINC00847, CDKN2A-DT, AL132800.1, GCC2-AS1, AC005746.1) using Lasso Cox regression analysis to develop an eight-CRL prognostic model. Patients were categorized into high- and low-risk groups using risk scores. To evaluate the predictive ability of the model, Kaplan-Meier analysis, ROC curves, and nomograms were employed. Furthermore, the study investigated the differences in immune function and anticancer drug sensitivity between the high- and low-risk groups. To validate the expression of CRLs in the model, OSCC cell lines were subjected to quantitative real-time fluorescence PCR (qRT-PCR).ResultsThe results of the study showed that the high-risk group had a shorter overall survival (OS) time in OSCC patients. Cox regression analysis demonstrated that the high-risk score was an independent risk factor for a poor prognosis. The validity of the model was confirmed using ROC curve analysis, and a nomogram was developed to predict the prognosis of OSCC patients. Furthermore, patients in the high-risk group with high TMB had a poorer prognosis. Patients in the low-risk group responded better to immunotherapy than those in the high-risk group. Additionally, the risk scores were significantly associated with drug sensitivity in OSCC patients. Finally, the findings of qRT-PCR supported the reliability of the proposed risk model.ConclusionThe study identified and established the 8-CRL model, which represents a novel pathway of lncRNA regulation of cuproptosis in OSCC. This model provides guidance for the prognosis and treatment of OSCC and offers a new insight into immune escape and tumor drug resistance.

Involvement of ferroptosis‐defensive xCT/GPX4 axis in radioresistance and its impacts on prognosis in oral squamous cell carcinoma

AbstractAimRadiotherapy, the mainstay treatment for patients with advanced oral squamous cell carcinoma (OSCC), has low clinical efficacy, resulting in poor prognosis. Radiation induces ferroptosis, a form of cell death driven by iron‐dependent lipid peroxidation. Since the xCT/glutathione peroxidase 4 (GPX4) axis is predominantly involved in the ferroptosis defense system, targeting this axis may potentiate cancer cell vulnerability to ferroptosis.MethodsWe examined the expression of xCT and GPX4 in the tumor cells of biopsy specimens using immunohistochemistry and evaluated the radiation‐mediated antitumor effects of the ferroptosis inducers, erastin and RSL3, that act by inhibiting xCT and GPX4, respectively.ResultsUnivariate analysis revealed that high immunohistochemical expression of xCT was correlated with shorter survival, and high GPX4 expression was an independent poor prognostic factor, indicating that the xCT/GPX4 axis influences the clinical outcome of OSCC. Analyses using two types of OSCC cell lines revealed that the clonogenic survival of irradiated cells was increased by the ferroptosis inhibitor ferrostatin‐1 and decreased by erastin and RSL3. The enhanced antitumor effects of erastin and RSL3 were accompanied by increased lipid peroxidation, which was suppressed by the iron chelator deferoxamine. Erastin and RSL3 enhance the effects of radiation on OSCC cells in a mouse xenograft model; these effects were associated with increased expression of the lipid peroxidation marker 4‐hydroxynonenal in tumor cells.ConclusionsxCT/GPX4 axis is involved in the tumor resistance against radiation through the inhibition of ferroptosis in OSCC. Furthermore, radiotherapy combined with ferroptosis induction by targeting the xCT/GPX4 axis may improve patient prognosis in advanced OSCC.

Development of a novel senescence-related gene signature to predict clinical outcomes, immune landscape, and chemotherapeutic sensitivity in oral squamous cell carcinoma.

Cellular senescence significantly associates with tumor initiation, progression, and therapeutic response across multiple cancers. Here, we sought to develop a novel senescence-related genes (SRGs)-derived signature for oral squamous cell carcinoma (OSCC) prognostication and therapeutic response prediction. OSCC-specific SRG prognostic signature was established with univariate Cox regression, Kaplan-Meier survival, and LASSO-penalized multivariate Cox regression analyses. A SRG nomogram integrating this signature and selected clinicopathological parameters were constructed by multivariate Cox regression. SiRNA-mediated gene knockdown was exploited to validate its function in vitro. The utilities of SRG signature in predicting immune status and chemotherapeutic sensitivities were analyzed. The prognostic performance of SRG signature/nomogram was satisfactory in multiple independent cohorts. CDK1 knockdown induced senescence phenotype in vitro. Moreover, SRG signature scores negatively correlated with tumor-infiltrating immune cells and associated with multiple chemotherapeutic drug sensitivities. Our results established SRG-derived signature/nomogram as powerful predictors for prognosis and chemotherapeutic response for OSCC.

Comprehensive Analysis of Oral Squamous Cell Carcinomas: Clinical, Epidemiological, and Histopathological Insights With a Focus on Prognostic Factors and Survival Time.

Oral squamous cell carcinoma(OSCC) is one of the most common malignancies in the head and neck region. Particularly, high incidence rates are observed in South and Southeast Asia, attributed to the widespread use of the carcinogenic areca nut. This study aimed to investigate the clinical, epidemiological, and histopathological features of OSCC, identify prognostic factors impacting disease-free survival, and determine a post-diagnosis disease-free survival time of OSCC patients. Employing a descriptive cross-sectional design, the study conducted a thorough examination of the clinical, epidemiological, and histopathological aspects of OSCC among patients seeking care at a tertiary healthcare facility. Participants were personally interviewed if available, while information for unreachable or deceased individuals was extracted from archival patient records in the Oral and Maxillofacial Surgery Department, Bakhtawar Amin Medical and Dental College, Multan, Pakistan. Data analysis was performed with a significance level set at p ≤ 0.05. The mean age of the patients was 54.16 ± 11.1, with a notable concentration in the 41 years and above age group, indicating a significant prevalence of OSCC in this population. The data revealed a gender bias towardmales, and a substantial proportion of patients, particularly those aged 41 years and above, had unfortunately passed away. Statistical analysis using the Fisher exact test showed a significant association between age groups and patients' current living status (p-value < 0.05). Histopathologically, moderately differentiated OSCC was the most frequently encountered grade, and surgery emerged as the predominant treatment modality. The majority of patients studied had a survival period of three years or less, emphasizing the need for further exploration of factors influencing prognosis and treatment outcomes in OSCC.

Prognostic significance of RKIP, TGM2, and CMTM4 expression in oral squamous cell carcinoma.

The expression of RKIP, TGM2, and CMTM4 in oral squamous cell carcinoma (OSCC) and normal oral tissues was detected and their correlations were analyzed. The relationships between RKIP, TGM2, and CMTM4 and the clinicopathological parameters and prognosis of patients were analyzed. Seventy cancerous and adjacent normal tissue samples were selected, recorded in the pathology department, and embedded in paraffin. Protein expression was detected by immunohistochemistry. Statistical software (SPSS 25.0, IBM Corporation) was used for the statistical analysis. The chi-squared (χ2) test was used to analyze the expression of RKIP, TGM2, and CMTM4 proteins and their clinicopathological features. Differences in RKIP, TGM2, and CMTM4 protein levels between OSCC and normal tissues were compared using a χ2 test. Survival analysis was performed using the Kaplan-Meier method, and differences between survival curves were determined using the log-rank test. The effects of RKIP, TGM2, and CMTM4 expression on patient prognosis were analyzed using a multivariate Cox proportional hazards regression model. P < .05 was considered statistically significant. The expression level of RKIP correlated with age and clinical stage (P < .05). TGM2 was associated with clinical stage and lymph node metastasis (P < .05). The expression of CMTM4 increased with a decrease in cancer differentiation. Kaplan-Meier survival analysis suggested that the positive expression of TGM2 and CMTM4 may predict poor prognosis in patients with OSCC. The multivariate Cox proportional hazards regression model suggested that TGM2 could be an independent prognostic factor for patients with OSCC. Combined expression of TGM2 and CMTM4 can be used as an indicator to evaluate the risk of metastasis and prognosis of OSCC.

Exploring beyond Common Cell Death Pathways in Oral Cancer: A Systematic Review.

Oral squamous cell carcinoma (OSCC) is the most common and lethal type of head and neck cancer in the world. Variable response and acquisition of resistance to traditional therapies show that it is essential to develop novel strategies that can provide better outcomes for the patient. Understanding of cellular and molecular mechanisms of cell death control has increased rapidly in recent years. Activation of cell death pathways, such as the emerging forms of non-apoptotic programmed cell death, including ferroptosis, pyroptosis, necroptosis, NETosis, parthanatos, mitoptosis and paraptosis, may represent clinically relevant novel therapeutic opportunities. This systematic review summarizes the recently described forms of cell death in OSCC, highlighting their potential for informing diagnosis, prognosis and treatment. Original studies that explored any of the selected cell deaths in OSCC were included. Electronic search, study selection, data collection and risk of bias assessment tools were realized. The literature search was carried out in four databases, and the extracted data from 79 articles were categorized and grouped by type of cell death. Ferroptosis, pyroptosis, and necroptosis represented the main forms of cell death in the selected studies, with links to cancer immunity and inflammatory responses, progression and prognosis of OSCC. Harnessing the potential of these pathways may be useful in patient-specific prognosis and individualized therapy. We provide perspectives on how these different cell death types can be integrated to develop decision tools for diagnosis, prognosis, and treatment of OSCC.

Prognostic DNA mutation and mRNA expression analysis of perineural invasion in oral squamous cell carcinoma

This study analyzed oral squamous cell carcinoma (OSCC) genomes and transcriptomes in relation to perineural invasion (PNI) and prognosis using Cancer Genome Atlas data and validated these results with GSE41613 data. Gene set enrichment analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted. We identified 22 DNA mutations associated with both overall survival (OS) and PNI. Among them, TGFBR1 and RPS6KA4 mRNAs were overexpressed, while TYRO3 and GPR137 mRNAs were underexpressed in PNI patients. Among the 141 mRNA genes associated with both OS and PNI, we found overlap with PNI-related DNA mutations, including ZNF43, TEX10, TPSD1, and PSD3. In GSE41613 data, TGFBR1, RPS6KA4, TYRO3, GPR137, TEX10 and TPSD1 mRNAs were expressed differently according to the prognosis. The 22 DNA-mutated genes clustered into nervous system development, regulation of DNA-templated transcription, and transforming growth factor beta binding. GSEA analysis of mRNAs revealed upregulation of hallmarks epithelial mesenchymal transition (EMT), TNFα signaling via NF-κB, and IL2 STAT5 signaling. EMT upregulation aligned with the TGFBR1 DNA mutation, supporting its significance in PNI. These findings suggest a potential role of PNI genes in the prognosis of OSCC, providing insights for diagnosis and treatment of OSCC.

Unravelling the heterogeneity of oral squamous cell carcinoma by integrative analysis of single-cell and bulk transcriptome data.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy of the head and neck with rising global incidence. Despite advances in treatment modalities, OSCC prognosis remains diverse due to the complex molecular and cellular heterogeneity within tumours, as well as the heterogeneity in tumour microenvironment (TME). In this study, we utilized single-cell RNA sequencing (scRNA-seq) analysis to explore distinct subpopulations of tumour cells in OSCC tissues and their interaction with components in TME. We identified four major tumour cell subpopulations (C0, C1, C2 and C3) with unique molecular characteristics and functional features. Pathway enrichment analysis revealed that C0 primarily expressed genes involved in extracellular matrix interactions and C1 showed higher proliferation levels, suggesting that the two cell subpopulations exhibited tumour aggressiveness. Conversely, C2 and C3 displayed features associated with keratinization and cornified envelope formation. Accordingly, C0 and C1 subpopulations were associated with shorter overall and disease-free survival times, while C2 and C3 were weakly correlated with longer survival. Genomic analysis showed that C1 demonstrated a positive correlation with tumour mutation burden. Furthermore, C0 exhibited resistant to cisplatin treatment, while C1 showed more sensitive to cisplatin treatment, indicating that C0 might exhibit more aggressive compared to C1. Additionally, C0 had a higher level of communication with fibroblasts and endothelial cells in TME via integrin-MAPK signalling, suggesting that the function of C0 was maintained by that pathway. In summary, this study provided critical insights into the molecular and cellular heterogeneity of OSCC, with potential implications for prognosis prediction and personalized therapeutic approaches.