Development Of Oral Squamous Cell Carcinoma Research Articles

LINC01614 Promotes Oral Squamous Cell Carcinoma by Regulating FOXC1

Background: Long non-coding RNAs (lncRNAs) are pivotal mediators during the development of carcinomas; however, it remains to be investigated whether lncRNAs are implicated in oral squamous cell carcinoma (OSCC). Methods: In this study, quantitative real-time PCR was conducted for detecting the expression of LINC01614 in OSCC cell lines. The biological functions of LINC01614 were assessed by loss- and gain-of-function experiments conducted both in vivo and in vitro. Cellular proliferation, migration, and invasion were investigated herein, and dual luciferase reporter assays were additionally performed to explore the relationships among LINC01614, miR-138-5p, and Forkhead box C1 (FOXC1). Results: The research presented herein revealed that OSCC cells express high levels of LINC01614. Functional experiments employing cellular and animal models demonstrated that LINC01614 knockdown repressed the malignant phenotypes of OSCC cells, including their growth, invasiveness, and migration. Further investigation revealed that LINC01614 absorbs miR-138-5p miRNA by functioning as a competing endogenous RNA to downregulate the abundance of FOXC1. Conclusions: The findings revealed that LINC01614 contributes to the progression of OSCC by targeting the FOXC1 signaling pathway. The study provides insights into a novel mechanistic process to regulate the development of OSCC, and established a possible target for the therapeutic management of OSCC.

Black raspberry modulates cecal and oral microbiome at the early stage of a dibenzo[def,p]chrysene-induced murine oral cancer model.

While tobacco smoking is a risk factor in the development of oral squamous cell carcinoma (OSCC), only a fraction of smokers develop the disease. Compelling evidence shows that microbial community composition is associated with carcinogenesis, suggesting that the microbiome may play a role in cancer development of smokers. We previously showed that black raspberry (BRB) protects against OSCC induced by the tobacco constituent dibenzo[def,p]chrysene (DBP) altering genetic and epigenetic markers in a manner consistent with its cancer preventive activity. In the present study, we conducted a mouse experiment to investigate the effects of BRB and DBP individually and in combination on the oral and gut microbiota. DBP-induced DNA damage in the mouse oral cavity which is an essential step for the development of OSCC in mice. 16S rRNA gene sequencing revealed that BRB significantly increased microbial diversity and shifted microbiome composition in the gut and oral cavity, whereas DBP had no significant effect. In both gut and oral microbiota, Akkermansia muciniphila was significantly reduced after BRB treatment; however, this was not consistent with pure culture in vitro assays suggesting that the impact of BRB on A. muciniphila may be mediated through indirect mechanisms including the host or other microbes. Indeed BRB, but not DBP, was found to modulate the growth kinetics of human gut microbes in vitro including lactic acid bacteria and Bacteroides spp. The results of the current study further emphasize the interplay of microbiome and environmental factors in the development and prevention of OSCC.

Changes of immune function mediated by Gasdermin-E in the immune microenvironment of primary oral squamous cell carcinoma

In primary oral squamous cell carcinoma (OSCC), the tumor microenvironment (TME) constitutes a highly intricate ecosystem comprised of cellular and acellular elements. The tumor immune microenvironment (TIME) is characterized by the presence of a broad of immune cells, while there is a scarcity of cytotoxic lymphocytes (CTLs) intratumorally. Consequently, the recruitment of a larger cohort of CTLs to infiltrate the tumor core has emerged as a pressing scientific challenge. Gasdermin E (GSDME), as a pivotal effector protein in pyroptosis, plays a significant role in anti-tumor therapy. Here, primary OSCC was induced by Gsdme knockout (KO) mice and wild type (WT) mice of the same strain respectively, using the chemical mutagen 4-Nitroquinoline N-oxide (4-NQO). Through comparative analysis of immune function between the two kinds of mice, intriguing observations have been elucidated, the presence of GSDME was instrumental in augmenting the infiltration of lymphocytes towards the neoplastic site, effectively ameliorating the TIME. Our findings elucidated that the absence of GSDME promotes the development of primary OSCC, accompanied by a notable increase in malignancy. Furthermore, our data delineated a positive inter-relationship between the presence of GSDME and the host organism’s immunological reactivity, which enhances the TIME in primary OSCC.

Integration of host gene regulation and oral microbiome reveals the influences of smoking during the development of oral squamous cell carcinoma.

This study aims to investigate the regulation of host gene transcription and microbial changes during the development of oral squamous cell carcinoma (OSCC) associated with smoking. The OSCC mouse model and smoking mouse model were established using 200 μg/mL 4-nitroquinoline-1-oxide (4NQO) in drinking water and exposure to cigarette smoke (four cigarettes per session, once a day, 5 days a week). Tongue tissues were harvested at 4 weeks and 16 weeks. Histopathological changes were evaluated using hematoxylin and eosin staining and Ki67 staining. RNA sequencing was performed on the mouse tongue tissues to identify differentially expressed genes (DEGs), and the results were validated by RT-PCR and immunohistochemistry. 16S rDNA sequencing was used to analyze changes in the oral microbiota during the early development of OSCC, identifying differentially abundant taxa associated with smoking. Finally, associations between the relative abundances of the oral microbiome and host gene expression were modeled using the Origin software. DEGs associated with smoking during the development of OSCC were identified. There were 12 upregulated genes, including NR4A3 and PPP1R3C, and 23 downregulated genes, including CD74 and ANKRD1. These genes were enriched in functions related to the signal transduction of cellular processes such as inflammation, differentiation, immunity, and PI3K/AKT, NF-κB signaling pathways. 4NQO and smoking treatment decreased oral microbial diversity and reduced the abundance of Bacteroidetes, Proteobacteria, and Lactobacillus but increased the abundance of Staphylococcus. Integrative analysis showed that the expression of CD74 was positively correlated with the relative abundance of Lactobacillus, while PPP1R3C was negatively correlated with Bacteroidota. In addition to characterizing host gene expression and the oral microbiome, our study explored the potential role of host-microbiome interactions in the development of OSCC. These findings enhance our understanding of smoking-related OSCC occurrence and development, providing new insights for its prevention.

Integrated analysis of gene expressions and targeted mirnas for explaining crosstalk between oral and esophageal squamous cell carcinomas through an interpretable machine learning approach.

This study explores the bidirectional relation of esophageal squamous cell carcinoma (ESCC) and oral squamous cell carcinoma (OSCC), examining shared risk factors and underlying molecular mechanisms. By employing random forest (RF) classifier, enhanced with interpretable machine learning (IML) through SHapley Additive exPlanations (SHAP), we analyzed gene expression from two GEO datasets (GSE30784 and GSE44021). The GSE30784 dataset comprises 167 OSCC samples and 45 control group, whereas the GSE44021 dataset encompasses 113 ESCC samples and 113 control group. Our analysis led to identification of 20 key genes, such as XBP1, VGLL1, and RAD1, which are significantly associated with development of ESCC and OSCC. Further investigations were conducted using tools like NetworkAnalyst 3.0, Single Cell Portal, and miRNET 2.0, which highlighted complex interactions between these genes and specific miRNA targets including hsa-mir-124-3p and hsa-mir-1-3p. Our model achieved high precision in identifying genes linked to crucial processes like programmed cell death and cancer pathways, suggesting new avenues for diagnosis and treatment. This study confirms the bidirectional relationship between OSCC and ESCC, laying groundwork for targeted therapeutic approaches. This study helps to identify shared biological pathways and genetic factors of these conditions for designing personalized medicine strategies and to improve disease management.

Inhibition of Benzo[a]pyrene-induced DNA Adduct in Buccal Cells of Smokers by Black Raspberry Lozenges.

Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage-induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in non-smokers; these results suggest the potential contribution of B[a]P in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC at late stages even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings we tested the hypothesis, in a Phase 0 clinical study, that BRB administration reduces DNA damage induced by B[a]P in buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected at four weeks after BRB cessation (washout period). B[a]P-induced DNA damage (BPDE-N2-dG) was evaluated by LC-MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (p = 0.01506) compared to baseline, 36.1% at the end of BRB administration (p = 0.00355), and 16.6% after BRB cessation (p = 0.007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC.

The effect of m6A methyltransferase METTL3 mediated TMEM30A regulation on tumor energy metabolism and cisplatin anti-tumor activity in oral squamous cell carcinoma

AimsCisplatin (CDDP) is still one of the most commonly used first-line treatments for advanced and recurrent oral squamous cell carcinoma (OSCC) patients in clinical practice. However, the decrease in tumor sensitivity to CDDP weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on CDDP sensitivity in OSCC. TMEM30A widely exists in biomembranes and regulates the lipid asymmetry of the membrane, but there is no report on its function in OSCC. This study aims to explore the specific mechanism by which METTL3 regulates m6A methylation of TMEM30A and affects the occurrence and development of OSCC, and further investigate the effects of METTL3 and TMEM30A on the anti-tumor activity of CDDP. Key findingsIn OSCC, METTL3 plays a pro-cancer role and weakens the anti-tumor efficacy of CDDP; METTL3 positively regulates the expression of TMEM30A by m6A methylation modification and binding to TMEM30A; The abnormally high expression of TMEM30A in OSCC not only weakens CDDP sensitivity, but also enhances the malignant evolution of cancer cells, regulates the metabolic balance of ATP and lactate in cells, and is a potential oncogenic gene. SignificanceTMEM30A promotes malignant progression of tumors through METTL3 mediated m6A methylation modification, participates in maintaining the balance of tumor ATP and lactate metabolism, and reduces the anti-tumor activity of CDDP. TMEM30A is a potential gene target for CDDP anti-tumor activity in OSCC.

PPT1 Promotes Growth and Inhibits Ferroptosis of Oral Squamous Cell Carcinoma Cells.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers with poor prognosis in the head and neck. Elucidating molecular mechanisms underlying OSCC occurrence and development is important for the therapy. Dysregulated palmitoylation-related enzymes have been reported in several cancers but OSCC. To explore the role of palmitoyl-protein thioesterase 1 (PPT1) in OSCC. Differentially expressed genes (DEGs) and related protein-protein interaction networks between normal oral epithelial and OSCC tissues were screened and constructed via different online databases. Tumor samples from 70 OSCC patients were evaluated for the relationship between PPT1 expression level and patients'clinic characteristics. The role of PPT1 in OSCC proliferation and metastasis was studied by functional experiments including MTT, colony formation, EdU incorporation and transwell assays. Lentivirus-based constructs were used to manipulate gene expression. FerroOrange probe and malondialdehyde assay were used to determine ferroptosis. Growth of OSCC cells in vivo was investigated by a xenograft mouse model. A total of 555 DEGs were obtained, and topological analysis revealed that PPT1 and GPX4 might play critical roles in OSCC. Increased PPT1 expression was found to be correlated with poor prognosis of OSCC patients. PPT1 effectively promoted the proliferation, migration and invasion while inhibited the ferroptosis of OSCC cells. PPT1 affected the expression of glutathione peroxidase 4 (GPX4). PPT1 promoted growth and inhibited ferroptosis of OSCC cells. PPT1 might be a potential target for OSCC therapy.

MiRNA99a as a Potential target in P13K/Akt1/mTOR signaling pathway in progression of OSCC

BackgroundOral cancer presents a significant global health challenge, driving ongoing research to enhance diagnostics and treatments. MicroRNAs, particularly miRNA99a, have emerged as key players in oral cancer's initiation, progression, and advanced development. However, their precise molecular mechanisms remain unclear. We analyze miRNA99a in modulating the PI3K/Akt1/mTOR signaling pathway within oral squamous cell carcinoma through in silico data analysis. Additionally, we examined miRNA99a levels in both oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC). Materials and MethodsA comprehensive approach utilizing various insilico tools identified potential target genes regulated by miRNA99a and examined their interactions within the PI3K/Akt1/mTOR signaling pathway. The study involved meticulous screening, functional enrichment analyses, and network analyses to understand the regulatory networks influenced by miRNA99a. Additionally, RT-PCR was used to measure the CT levels of miR-99a in OSMF, OSCC and NM samples. ResultsThe analysis revealed a cohort of putative target genes regulated by miRNA99a, demonstrating their involvement in crucial cellular processes linked to OSCC progression. Functional enrichment analyses highlighted the significant association of these target genes with the PI3K/Akt1/mTOR pathway, indicating their potential impact on pivotal oncogenic signaling pathways. Network analyses revealed complex regulatory networks orchestrated by miRNA99a, its action within the PI3K/Akt1/mTOR signalling pathway and influencing OSCC development. RT-PCR analysis revealed a significant downregulation of miR-99a in OSCC and OSMF samples compared to NM, with mean CT values of 39.0940 and 38.3986 respectively, versus 33.7540 in NM (p = 0.000). ConclusionmiRNA99a's potential as a crucial regulator of the PI3K/Akt1/mTOR pathway in OSCC. The identified target genes and their interactions offer a foundation for further experimental validations, presenting opportunities for discovering novel therapeutic avenues or prognostic markers in managing OSCC. Integrating multi-omics data reinforces the significance of miRNA99a-mediated regulatory mechanisms in the intricate landscape of oral cancer biology.

The Role of Ryanodine Receptor 2 Polymorphisms in Oral Squamous Cell Carcinoma Susceptibility and Clinicopathological Features.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is one of the most common types. There is strong evidence that ryanodine receptor 2 (RYR2) plays an important role in different types of cancer according to previous studies. Its expression is associated with survival in patients with HNSCC, but it is unknown whether altered RYR2 expression contributes to tumorigenesis. Therefore, we examined how RYR2 polymorphisms affect OSCC susceptibility and clinicopathological characteristics. Five single nucleotide polymorphisms (SNPs) of RYR2, rs12594, rs16835904, rs2779359, rs3765097, and rs3820216, were analyzed in 562 cases of OSCC and 332 healthy controls using real-time PCR. We demonstrated that RYR2 SNP rs12594 was significantly different between the case and control groups, but this difference was not significant after adjusting for personal habits. In contrast, we found that different genotypes of SNP rs2779359 were significantly associated with the characteristics of clinical stage and tumor size in OSCC patients, according to the odds ratios and the adjusted odds ratios; specifically, patients with the T genotype had 1.477-fold (95% CI, 1.043 to 2.091; p = 0.028) and 1.533-fold (95% CI, 1.087-2.162; p = 0.015) increases in clinical stage and tumor size, respectively, compared with patients with the C allele. The results of our study, in which RYR2 SNPs associated with OSCC progression and development were examined for the first time, suggest that clinicopathological characteristics may alter OSCC susceptibility. Finally, RYR2 SNP rs2779359 not only plays a role in both the prognosis and diagnosis of oral cancer but is also likely an important predictive factor for recurrence, response to treatment, and medication toxicity.

16S rRNA based metagenomic analysis unveils unique oral microbial signatures in oral squamous cell carcinoma cases from Coastal Karnataka, India.

Oral Squamous cell carcinoma (OSCC) is the 14th most frequent cancer with 300,000 new cases and 100,000 deaths reported annually. Even with advanced therapy, the treatment outcomes are poor at advanced stages of the disease. The diagnosis of early OSCC is of paramount clinical value given the high mortality rate associated with the late stages of the disease. Recently, the role of microbiome inthedisease manifestation, including oral cancer, has garnered considerable attention. But, to establish the role of bacteria in oral cancer, it is important to determine the differences in the colonization patternin non-tumour and tumour tissues. In this study, 16S rRNA based metagenomic analyses of 13tumorous and contralateral anatomically matched normal tissue biopsies, obtained from patients with advanced stage of OSCC were evaluated to understand the correlation between OSCC and oral microbiome. In this study we identified Fusobacterium, Prevotella, Capnocytophaga, Leptotrichia, Peptostreptococcus, Parvimonas and Bacteroidetes as the most significantly enriched taxa in OSCC lesions compared to the non-cancerous tissues. Further, PICRUSt2 analysis unveiled enhanced expression of metabolic pathways associated with L-lysine fermentation, pyruvate fermentation, and isoleucine biosynthesis in those microbes associated with OSCC tissues. These findings provide valuable insights into the distinctive microbial signatures associated with OSCC, offering potential biomarkers and metabolic pathways underlying OSCC pathogenesis. While our focus has primarily centred onmicrobial signatures, it is essential to recognize the pivotal role of host factors such as immune responses, genetic predisposition, and the oral microenvironment in shaping OSCC development and microbiome composition.

Microbial community composition in subgingival plaques and heterogeneity of tumor tissue TCRβ CDR3 repertoire in patients with moderate-to-severe periodontitis and oral squamous cell carcinoma.

The human oral cavity contains over 700 types of bacteria that may protect the body against colonization by exogenous pathogens and maintain relative homeostasis. However, alterations in the immune status can disrupt the balance between microorganisms and the host, inducing various diseases such as oral cancer and diabetes mellitus. The mechanism underlying this process is not clearly understood. The purpose of this study was to investigate the relationships between subgingival bacteria, T-cell receptor β-chain complementarity-determining region 3 (TCRβ CDR3), and the development oforal squamous cell carcinoma (OSCC). We grouped patients as "healthy periodontal" (H), "moderate-to-severe chronic periodontitis" (C), and "moderate-to-severe chronic periodontitis with OSCC" (T). Bacterial groups were "subgingival plaque" (bp) and "gingival/tumor tissue" (g). We also recorded patients' age, gender, attachment level (AL), bleeding on probing (BOP), and probing depth (PD). We extracted and sequenced RNA from plaques, gingival tissues, tumors, and teeth. We performed high-throughput sequencing on TCRβ CDR3 and plaque bacteria. Synergistetes and Veillonella parvula were more abundant in the H group than in the T group. Granulicatella, Peptostreptococcus, and Streptococcus infantis were enriched in the T-bp group. AL, BOP, and PD were positively correlated with Granulicatella, Peptostreptococcus, and Pseudomonas but negatively correlated with Prevotella nigrescens and V. parvula. TCRβ CDR3 diversity was C > H > T. TCR β-chain Variable gene (TRBV)20-1 usage varied among the H, C, and T groups. TRBV2 and TRBV5-1 usage was greater in the T group than in the C group. TRBJ1-1, TRBJ1-2, TRBJ2-2, TRBJ2-7, and TRBJ2-5 were most frequently used. These trends and the reduction of gingival Synergistetes were correlated with OSCC. TCRβ CDR3 diversity was the lowest in patients in the T group, and there were considerable changes in the expression of TRBV2 and TRBJ. Therefore, plaque bacterial composition can influence TCRβ CDR3.

The Impact of Oral Microbiome Dysbiosis on the Aetiology, Pathogenesis, and Development of Oral Cancer.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Although the oral cavity is an easily accessible area for visual examination, the OSCC is more often detected at an advanced stage. The global prevalence of OSCC is around 6%, with increasing trends posing a significant health problem due to the increase in morbidity and mortality. The oral cavity microbiome has been the target of numerous studies, with findings highlighting the significant role of dysbiosis in developing OSCC. Dysbiosis can significantly increase pathobionts (bacteria, viruses, fungi, and parasites) that trigger inflammation through their virulence and pathogenicity factors. In contrast, chronic bacterial inflammation contributes to the development of OSCC. Pathobionts also have other effects, such as the impact on the immune system, which can alter immune responses and contribute to a pro-inflammatory environment. Poor oral hygiene and carbohydrate-rich foods can also increase the risk of developing oral cancer. The risk factors and mechanisms of OSCC development are not yet fully understood and remain a frequent research topic. For this reason, this narrative review concentrates on the issue of dysbiosis as the potential cause of OSCC, as well as the underlying mechanisms involved.

The paradoxical role of transforming growth factor-β in controlling oral squamous cell carcinoma development.

Transforming growth factor-β (TGF-β) is a multifunctional cytokine that plays a vital role in regulating cell growth, differentiation and survival in various tissues. It participates in a variety of cellular processes, including cell apoptosis, cell migration and evasion, and plays a paradoxical role in tumor genesis and development. In the early stage of tumor, TGF-β inhibits the occurrence of tumor by inhibiting cell proliferation and regulating cell apoptosis. In the advanced stage of tumor, TGF-β promotes tumor development and affects prognosis by promoting cell survival and proliferation, cell migration and invasion, participates in immune escape, etc. In this article, we will review the paradoxical role of TGF-β on the occurrence and development of oral squamous cell carcinoma.

Silencing ANLN hinders the proliferation, migration, invasion, and angiogenesis of oral squamous cell carcinoma

BackgroundThe actin-binding protein anillin (ANLN) functions as an oncogene in various cancers but has not been fully studied in oral squamous cell carcinoma (OSCC). This study aimed to investigate the expression of ANLN in OSCC tissues and cell lines, to better understand its role in mediating proliferative, angiogenic, invasive, and metastatic capabilities in this type of cancer. MethodsANLN mRNA and protein levels were assessed using qPCR and western immunoblotting. The expression intensity of ANLN was evaluated using immunohistochemical (IHC) staining. Biological functional assays were employed to characterize the behavior of OSCC cells influenced by ANLN. Additionally, comprehensive bioinformatics analysis, including GO analysis and KEGG enrichment analysis, was performed on differentially expressed genes in ANLN-mediated pathways. ResultsOSCC tumors and cell lines exhibited higher ANLN expression. Silencing of ANLN significantly suppressed OSCC cell proliferation, as evidenced by a significant reduction in the Ki-67 index both in vitro and in vivo. The migration and invasive ability of OSCC cells were markedly diminished, coinciding with a decrease in epithelial-mesenchymal transition activity. ANLN was also found to promote angiogenic activity in OSCC cells, partly through synergistic effects mediated by vascular endothelial growth factor A (VEGFA). Downregulation of ANLN expression led to decreased VEGFA levels, resulting in reduced angiogenesis characterized by fewer vascular branches. ConclusionsOur findings highlight the promising role of ANLN as a biomarker for both diagnostic and prognostic in OSCC. Targeting ANLN with inhibitory strategies could impede the oncogenesis processes at the core of OSCC development, presenting significant opportunities for advancing therapeutic interventions.

Correlation between serum heavy metals and the risk of oral squamous cell carcinoma and oral potentially malignant disorders

Oral squamous cell carcinoma (OSCC) is a serious public health problem in various Asian countries, including Sri Lanka, and a combination of cultural practices, lifestyle factors, and genetic predispositions influences the incidence of these cancers. The examination of the connection between exposure to heavy metals and the probability of developing oral potentially malignant disorders (OPMD) and OSCC has been limited in its scope, and the overall consequences of such exposure remain largely unknown. This study aims to clarify the link between serum levels of heavy metals and the risk of OSCC and OPMD. The concentrations of seven heavy metals—namely, arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), lead (Pb), and zinc (Zn)—were analyzed in serum samples from 60 cases and 15 controls in the Sri Lankan cohort. The Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) was used for the analysis. Subsequently, the data underwent statistical evaluation via the Kruskal–Wallis H test, using the Statistical Package for Social Sciences (SPSS) version 28 software, with a confidence interval set at 95%. A p-value less than 0.05 was considered statistically significant. The cohort consisted of 48 men and 27 women, with 15 patients each diagnosed with OSCC, OSF, OLK, and OLP, and 15 healthy controls. The study used the Kruskal–Wallis Test to compare metal concentrations across groups, finding significant differences for all metals except As and Pb. Significant associations were observed between age, past medical history, drug history, gender, smoking, alcohol consumption, and betel chewing. The Spearman Correlation test showed significant correlations between the concentrations of Cr, Co, Cu, As, and Zn and the presence of cancer/precancer conditions. The study’s findings suggest that heavy metal contamination may be linked to the development of OSCC and precancerous conditions. When comparing OSCC and OPMD cases with controls, the serum concentrations of As and Pb did not differ significantly. However, Cd, Cr, Co, Cu, and Zn exhibited significantly higher concentrations among cases compared to controls (p < 0.05). This study observed significant variations in the levels of these five heavy metals among cancerous (OSCC), premalignant (OPMD), and healthy tissues, suggesting a potential role in the progression of malignancies. These findings underscore the importance of environmental pollution in this specific context.

Biomarkers Identification in the Microenvironment of Oral Squamous Cell Carcinoma: A Systematic Review of Proteomic Studies.

An important determinant for oral squamous cell carcinoma (OSCC) onset and outcome is the composition of the tumor microenvironment (TME). Thus, the study of the interactions occurring among cancer cells, immune cells, and cancer-associated fibroblasts within the TME could facilitate the understanding of the mechanisms underlying OSCC development and progression, as well as of its sensitivity or resistance to the therapy. In this context, it must be highlighted that the characterization of TME proteins is enabled by proteomic methodologies, particularly mass spectrometry (MS). Aiming to identify TME protein markers employable for diagnosing and prognosticating OSCC, we have retrieved a total of 119 articles spanning 2001 to 2023, of which 17 have passed the selection process, satisfying all its criteria. We have found a total of 570 proteins detected by MS-based proteomics in the TME of OSCC; among them, 542 are identified by a single study, while 28 are cited by two or more studies. These 28 proteins participate in extracellular matrix remodeling and/or energy metabolism. Here, we propose them as markers that could be used to characterize the TME of OSCC for diagnostic/prognostic purposes. Noteworthy, most of the 28 individuated proteins share one feature: being modulated by the hypoxia that is present in the proliferating OSCC mass.

DAZAP1 Phase Separation Regulates Mitochondrial Metabolism to Facilitate Invasion and Metastasis of Oral Squamous Cell Carcinoma.

Tumor invasion and metastasis are the underlying causes of the high mortality rate of oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial-mesenchymal transition (EMT). RNA-seq analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid-liquid phase separation (LLPS) to accumulate in the nucleus where it enhanced cytochrome-c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In OSCC patient samples, expression of DAZAP1 positively correlated with COX16, and high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis.

The efficacy and potential mechanisms of pyrotinib in targeting EGFR and HER2 in advanced oral squamous cell carcinoma

BackgroundHuman epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined.Methods57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR.ResultsThis study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK.ConclusionsThis study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment.

MiRNA genetic variations associated with the predisposition of oral squamous cell carcinoma in central Indian population

The disease burden of Oral Squamous Cell Carcinoma (OSCC) is rising day-by-day and is expected to rise 62 % through 2035. The chewing of tobacco, areca nut, and betel leaf, poor oral hygiene, and chronic infection are common risk factors of OSCC, but genetic and epigenetic factors also contribute equally. MicroRNAs (miRNAs) are comprised of small, non-coding endogenous RNA that regulate a plethora of biological activities by targeting messenger RNA through degradation or inhibition. Single Nucleotide Polymorphisms (SNPs) in miRNA genes can regulate the development and progression of OSCC. The present study aimed to determine the association between SNPs in miRNA genes (miRSNPs) with the risk of OSCC. A case-control study involving 225 histo-pathologically confirmed OSCC cases and 225 healthy controls was conducted, where 25 miRSNPs were analyzed by iPLEX MassArray analysis. A SNP rs12220909 in MIR4293 showed a highly protective effect (CC vs GG, OR = 0.0431, 95%CI = 0.005–0.323, p = 3e-6). Whereas three SNPs, namely, rs4705342 in MIR143 (CC vs TT, OR = 2.25, 95%CI = 2.00–2.53, p = 0.0008), rs531564 in MIR124 (CC vs GG, OR = 24.18, 95%CI = 3.22–181.37, p = 3e-6), and rs3746444 in MIR499 (AA vs GG, OR = 2.01, 95%CI = 1.32–3.05, p = 0.001) were significantly associated with a higher risk of OSCC. Additionally, NanoString-based nCounter miRNA expression profiling revealed that miR-499a (Log2FC = −1.07), and miR-143 (Log2FC = −1.56) were aberrantly expressed in OSCC tissue. Taken together, the above miSNPs may contribute to the high incidence of OSCC in central India. However, further studies with large cohorts and ethnic stratification are required to validate our findings.