Pathogenesis Of Oral Squamous Cell Carcinoma Research Articles

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.

Identification of novel genetic variants associated with oral squamous cell carcinoma (OSCC) in South-West coast of India using targeted exome sequencing

Oral squamous cell carcinoma (OSCC) is a subset of head and neck squamous cell carcinoma (HNSCC). This study explores the genetic landscape of oral squamous cell carcinoma (OSCC) in a cohort of 33 patients from Southern India using targeted exome sequencing. Our analysis revealed a diverse range of mutations across the cohort, with missense mutations being the most prevalent. Pathogenic mutations, as classified by ClinVar, exhibited significant individual variation, highlighting the heterogeneity of OSCC. Seventy-five genes were identified to harbor pathogenic or potentially pathogenic mutations, with notable recurrence in genes such as TP53, PDGFRA, and RAD50 among others. Comparison with high-frequency mutation genes in HNSCC from TCGA database revealed significant overlap, emphasizing the relevance of these mutations across different populations. Additionally, several novel mutations were identified, including those in CHD8, ITPKB, and HNF1A, shedding light on potential genetic risk factors specific to this population. Functional annotation and pathway analysis underscored the involvement of these mutated genes in various cancer-related pathways. Despite limitations such as sample size and the need for further validation, this study contributes to a deeper understanding of OSCC pathogenesis and highlights potential genetic markers for prognosis and targeted interventions, especially in the Indian context.

EZH2 Inhibition to Counteract Oral Cancer Progression through Wnt/β-Catenin Pathway Modulation.

Oral squamous cell carcinoma (OSCC) is one of the most common human malignancies worldwide. The molecular mechanisms of OSCC pathogenesis are still unknown; however, in recent years, several reports have focused on the role of enhancer of zeste homolog 2 (EZH2) in OSCC. Therefore, in this study we aimed to investigate the effects of GSK343, a selective EZH2 inhibitor, and its impact on the signaling pathways in OSCC, using an in vitro and in vivo orthotopic model. In the in vitro model, GSK343 (1, 10, and 25 μM) significantly decreased OSCC cell viability and cell migration through EZH2 inhibition, modulating NF-κB/IκBα pathway activation and eNOS, VEGF, and TGFβ expression, important markers of angiogenesis. In the in vivo model, GSK343 (5 mg/kg and 10 mg/kg) restored tongue tissue architecture and reduced tumor progression through EZH2 inhibition and Wnt/β-catenin signaling pathway modulation. Moreover, GSK343 reduced the expression of inflammatory mediators; eNOS and TGFβ, markers of angiogenesis; and CD31 and CD34, markers of micro vessel density, respectively. In conclusion, our data demonstrate that GSK343 counteracts oral cancer progression through EZH2/Wnt/β-catenin pathway modulation, suggesting that it could be a promising therapeutic approach for OSCC management.

Noncanonical formation of SNX5 gene-derived circular RNA regulates cancer growth

Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5’s tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA’s regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.

Analysis of methylation-driven genes for predicting the prognosis of patients with oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy that is characterized by early distant metastasis and poor prognosis. DNA methylation plays an important role in the etiology and pathogenesis of OSCC. This study aimed to identify methylation-driven genes through bioinformatics analysis as potential biomarkers for early diagnosis and prognostic assessment of OSCC. Methylation data, RNA sequencing (RNA-seq) data and clinical prognosis information of OSCC patients were retrieved from The Cancer Genome Atlas (TCGA) database. The R packages MethylMix were employed to analyze the correlation between methylation status and corresponding gene expression in tumor and normal tissues to obtain methylation-driven genes. Univariate Cox regression analysis was developed to further screen methylation-driven genes associated with the prognosis of OSCC patients. Subsequently, multivariate Cox regression analysis was utilized to construct a linear prognostic risk prediction model. Furthermore, a combined survival analysis integrating methylation and gene expression was performed to investigate the prognostic value. A total of 374 differentially expressed methylation-driven genes were identified. Seven methylation-driven genes (BST2, KRT15, ZNF134, NT5E, GSTA7P, NAPRT, and GOLPH3L) were found to be significantly associated with patient prognosis. Additionally, four methylation-driven genes (BST2, KRT15, ZNF134 and NAPRT) were used to construct a linear prognostic risk prediction model for OSCC patients. Furthermore, a combined Kaplan-Meier survival analysis revealed that three methylation-driven genes (ZKSCAN7, MFF, ZNF134) alone can be used as independent prognostic markers or drug targets. Our findings facilitate a better understanding of molecular mechanisms of OSCC and provide potential biomarkers of early diagnosis, precision treatment and prognosis evaluation.

SP110 Could be Used as a Potential Predictive and Therapeutic Biomarker for Oral Cancer.

The morbidity of oral squamous cell carcinoma (OSCC) has been rising year after year, making it a major global health issue. But the molecular pathogenesis of OSCC is currently unclear. To study the potential pathogenesis of OSCC, the differentially expressed genes (DEGs) were screened, and multiple databases were used to perform the tumor stage, expression, prognosis, protein-protein interaction (PPI) networks, modules, and the functional enrichment analysis. Moreover, we have identified SP110 as the key candidate gene and conducted various analyses on it using multiple databases. The research indicated that there were 211 common DEGs, and they were enriched in various GO terms and pathways. Meanwhile, one DEG is significantly related to short disease-free survival, four are associated with overall survival, and 12 DEGs have close ties with tumor staging. Additionally, the SP110 is significantly associated with methylation level, HPV status, tumor staging, gender, race, tumor grade, age, and overall/disease-free survival of oral cancer patients, as well as the immune process. The copy number variation of SP110 significantly affected the abundance of immune infiltration. Therefore, we speculate that SP110 could be used as the diagnostic and therapeutic biomarker for OSCC, and can help to further understand oral carcinogenesis.

Identification of KIF26B as a Tumor Marker for Oral Squamous Cell Carcinoma.

Kinesin family member 26B (KIF26B) has been closely linked to the occurrence and progression of various tumors. However, there is limited research on its role in oral squamous cell carcinoma (OSCC). This article aims to investigate the expression levels and mechanisms of KIF26B in OSCC. Real time quantity polymerase chain reaction (RT-qPCR) and Western blot analyses were conducted to assess the expression levels of KIF26B in 35 OSCC specimens and their corresponding non-cancerous tissues. Overexpression and silencing of KIF26B were achieved in HSC6 and SCC25 cells, respectively, resulting in the establishment of KIF26B-overexpressing and si-KIF26B cell lines, designated as the KIF26B group and si-KIF26B group. Proliferation assays using 5-Ethynyl-2'-deoxyuridine (EdU) labeling and clone formation were performed to evaluate the proliferative capacity of cells in these groups. The invasive and migratory abilities of cells in the KIF26B and si-KIF26B groups were assessed using Transwell assay. Additionally, the influence of KIF26B on the glycogen synthase kinase (GSK)-3β/β-catenin pathway was investigated through Western blot analysis. According to the results of RT-qPCR and Western blot analyses, the expression of KIF26B was predominantly higher in OSCC tissues compared to normal tissues (p < 0.01). Overexpression of KIF26B notably accelerated cell migration, invasion, and proliferation (p < 0.01), whereas knockdown of KIF26B significantly inhibited these processes (p < 0.01). Additionally, KIF26B overexpression led to increased levels of active β-catenin, p-GSK-3, and c-myc (p < 0.01), while KIF26B silencing decreased the levels of these proteins (p < 0.01). Our findings suggest that KIF26B may play a role in the pathogenesis and progression of OSCC as an oncogene. This study establishes a foundation for the identification of potential therapeutic targets for OSCC.

Elucidating the Role of Let-7d-5p and OLR1 in the Progression and Prognosis of Oral Squamous Cell Carcinoma via FAK/P53 Signaling Axis.

Despite advances in oral squamous cell carcinoma (OSCC) diagnosis and treatment, the five-year survival rate remains low, underscoring the need for improved biomarkers and therapeutic strategies. This study investigated the role of let-7d-5p microRNA (miRNA) and its target gene OLR1 in OSCC, focusing on their implications in tumor progression, metastasis and potential as therapeutic targets. Employing next-generation sequencing and bioinformatic tools, we profiled differentially expressed miRNAs in metastatic OSCC cell lines, identifying let-7d-5p as a key down-regulated miRNA and OLR1 as a novel target of let-7d-5p. We validated this interaction using luciferase reporter assays and studied the biological effects of modulating let-7d-5p and OLR1 expression on OSCC cell proliferation, migration, invasion, and stemness. Additionally, we analyzed clinical data to establish the relevance of OLR1 expression in OSCC prognosis. Our findings revealed let-7d-5p as a potent suppressor of OSCC metastasis, primarily by targeting and down-regulating OLR1. OLR1-silencing reduced OSCC cell invasiveness, migration, and stemness, indicating its prominent role in tumor progression. Mechanistically, let-7d-5p modulates a signaling cascade involving FAK, SRC, PAXILLIN, and p53, influencing cellular apoptosis and chemoresistance. Clinically, elevated OLR1 expression significantly correlates with advanced OSCC stages and poorer survival rates, highlighting its potential as a prognostic marker and therapeutic target. Our study uncovers the significance of the let-7d-5p-OLR1 axis in OSCC pathogenesis, offering novel insights for future therapeutic interventions.

Intronic miR-6741-3p targets the oncogene SRSF3: Implications for oral squamous cell carcinoma pathogenesis.

Epigenetic silencing through methylation is one of the major mechanisms for downregulation of tumor suppressor miRNAs in various malignancies. The aim of this study was to identify novel tumor suppressor miRNAs which are silenced by DNA hypermethylation and investigate the role of at least one of these in oral squamous cell carcinoma (OSCC) pathogenesis. We treated cells from an OSCC cell line SCC131 with 5-Azacytidine, a DNA methyltransferase inhibitor, to reactivate tumor suppressor miRNA genes silenced/downregulated due to DNA methylation. At 5-day post-treatment, total RNA was isolated from the 5-Azacytidine and vehicle control-treated cells. The expression of 2,459 mature miRNAs was analysed between 5-Azacytidine and control-treated OSCC cells by the microRNA microarray analysis. Of the 50 miRNAs which were found to be upregulated following 5-Azacytidine treatment, we decided to work with miR-6741-3p in details for further analysis, as it showed a mean fold expression of >4.0. The results of qRT-PCR, Western blotting, and dual-luciferase reporter assay indicated that miR-6741-3p directly targets the oncogene SRSF3 at the translational level only. The tumor-suppressive role of miR-6741-3p was established by various in vitro assays and in vivo study in NU/J athymic nude mice. Our results revealed that miR-6741-3p plays a tumor-suppressive role in OSCC pathogenesis, in part, by directly regulating SRSF3. Based on our observations, we propose that miR-6741-3p may serve as a potential biological target in tumor diagnostics, prognostic evaluation, and treatment of OSCC and perhaps other malignancies.

Deciphering the role of TLR3 polymorphisms in oral squamous cell carcinoma pathogenesis: A case-control study.

Oral squamous cell carcinoma (OSCC) poses a significant global health burden, particularly prevalent in regions like India. Despite advancements in diagnostics, early detection of OSCC remains challenging, necessitating novel diagnostic modalities. Toll-like receptors (TLRs) and their polymorphisms have emerged as potential contributors to OSCC pathogenesis. This retrospective case-control study examined 120 individuals, including 60 OSCC cases and 60 healthy controls. Genotyping of TLR3 single-nucleotide polymorphisms (SNPs) rs3775290 and rs3775291 was conducted using TaqMan allelic discrimination real-time polymerase chain reaction. Functional consequence analysis and TLR3 expression profiling were performed to elucidate their role in OSCC pathogenesis. Significant associations were observed between TLR3 SNPs and OSCC susceptibility, particularly at loci rs3775290 and rs3775291. Functional consequence analysis revealed pathogenic mutations in TLR3 genes, potentially affecting protein structure and function. TLR3 overexpression was detected in OSCC lesions, implicating its involvement in disease progression. TLR3 polymorphisms play a pivotal role in OSCC pathogenesis, offering potential biomarkers for diagnosis and prognosis. Targeting TLR3-mediated pathways may hold promise in personalised OSCC management. Further research is warranted to elucidate the precise mechanisms underlying TLR3-mediated carcinogenesis in OSCC, facilitating the development of tailored therapeutic strategies.

Waterpipe smoke condensate induces epithelial-mesenchymal transformation and promotes metastasis of oral cancer by FOXD1 expression

Background/purposeSmoking is a major contributor to global oral cancer cases, necessitating urgent intervention. FOXD1, involved in developmental processes and various cancers, shows promise as a prognostic marker in oral squamous cell carcinoma (OSCC). This study investigates the impact of waterpipe smoke condensate (WPSC) on OSCC, focusing on FOXD1 role in inducing epithelial-mesenchymal transition (EMT) and metastasis. MethodsThe study involved using OSCC cells treated with WPSC to evaluate their proliferation, colony formation, gene expression, and protein levels. The researchers also explored the clinical relevance of their findings using online databases to analyze FOXD1 expression in cancer tissues and its correlation with clinicopathological features and patient survival. Additionally, in silico tools were employed for functional analysis, pathway enrichment, and network exploration. ResultsThe study found that WPSC increased the expression of FOXD1 in OSCC cells, which led to increased cell growth. The study also showed that FOXD1 plays a critical role in the EMT process induced by WPSC, as evidenced by changes in the expression of EMT-related genes and proteins. Clinical analysis revealed that FOXD1 was significantly associated with more aggressive tumor features and poorer prognosis in cancer patients. ConclusionThe study highlights FOXD1 as a key player in OSCC pathogenesis and a potential prognostic marker and therapeutic target, particularly when influenced by WPSC exposure. Further research is needed to explore FOXD1 molecular mechanisms and clinical implications to enhance OSCC treatment strategies.

Plausible mechanisms in malignisation of non-habit related chronic nonhealing traumatic ulcers of oral cavity.

Chronic nonhealing ulcers of the oral mucosa and lateral tongue, in particular, can transform into invasive oral squamous cell carcinoma (OSCC). Sometimes these ulcers do not heal even after the removal of the etiological agent that actually initiated these lesions, something similar to what happens in "neoplasia." Numerous factors have been postulated in the literature; however, the exact mechanism remains unclear. We hereby would suggest few plausible factors that could be considered for future studies to shed light on some untapped territories in the pathogenesis of OSCC arising from chronic nonhealing traumatic ulcers in purview of chromoanagenesis and the concepts of "quantum entanglement and coherence."

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.

Expression of IGF-1R in oral submucous fibrosis and oral squamous cell carcinoma – An RT-PCR study

ObjectivesWith the rising number of cases of oral submucous fibrosis (OSMF) undergoing malignant transformation into oral squamous cell carcinoma (OSCC), it is needed to detect the changes at the earliest. Several molecular markers have been used for this purpose, and insulin-like growth factor receptor 1 (IGF-1R) is one of the markers in vogue for several human malignancies. Thus, we compared the expression of IGF-1R mRNA in normal oral mucosa (NOM), OSMF, and OSCC. Materials and methodsThirty biopsy tissue samples for each of the three groups, NOM, OSMF, and OSCC, were taken and analyzed histopathologically and then subjected to RT-PCR for evaluation of the expression of IGF-1R mRNA in each of them. ResultsThere was an upregulation of IGF-1R mRNA in OSMF tissue samples as compared to NOM, but a downregulation as compared to OSCC. There was a 3.24-fold upregulation of IGF-1R mRNA expression in OSMF as compared to NOM and a 1.31-fold downregulation as compared to OSCC. Likewise, there was a 4.2-fold upregulation of IGF-1R mRNA expression in OSCC as compared to NOM and 1.31-fold upregulation as compared to OSMF. Moreover, the expression was more in OSMF patients with interincisal opening (IIO) < 27 mm as compared to those with IIO >27 mm and also was found to increase with the grade of OSCC. ConclusionThe study reflected a potential role of IGF-1R in the pathogenesis of OSMF and OSCC, thus implying its possible exploitation as a diagnostic and prognostic marker and also as a therapeutic target in future.

Role of RUNX2 in Oral Squamous Cell Carcinoma (OSCC): A Systematic Scoping Review

RUNX2, known as the core-binding factor subunit alpha-1 (Cbfa1), is a protein-coding gene recognized and responsible for its involvement in bone development and osteoblast differentiation. However, its dysregulation and aberrant expression have been linked to the pathogenesis of many diseases, such as oral squamous cell carcinoma (OSCC). This review highlights the significance of the RUNX2 gene in oral squamous cell carcinoma. Objectives. To review the contribution of the RUNX2 gene in oral squamous cell carcinoma and its implication on clinical diagnosis and treatments. Materials and Methods. A systematic scoping review was conducted to elucidate the role of RUNX2 in OSCC. A framework of five stages for scoping reviews outlined by Arksey and O’Malley (2005) was adopted for the current study. Results. The review showed that RUNX2 plays a role in the development and progression of OSCC, a common form of head and neck cancer. Conclusion. RUNX2 is an essential player in the molecular mechanisms underlying the development and progression of oral squamous cell carcinoma, and its dysregulation promotes tumor initiation, progression, and metastasis, making it a potential target therapy for future research aimed at developing novel therapies for oral squamous cell carcinoma. Clinical Relevance. Understanding the precise mechanisms by which RUNX2 contributes to OSCC pathogenesis can lead to target treatment for this challenging form of cancer.

TCGA-based analysis of oncogenic signaling pathways underlying oral squamous cell carcinoma

Abstract Background Oral squamous cell carcinoma (OSCC) represents a prevalent malignancy in the oral and maxillofacial area, having a considerable negative impact on both the quality of life and overall survival of affected individuals. Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways, with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis, and thus laying the groundwork for the development of more effective therapeutic and preventive strategies. Methods Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC, using The Cancer Genome Atlas database. Predictions of oncogenic signaling pathways linked to differentially expressed mRNAs were made, and these results were presented visually using R software, using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments. Results GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes. Notably, these processes were related to the extracellular matrix, structural organization, connective tissue development, and cell cycle regulation. Conclusions The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.

TLR9 activation induces immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, and metastasis and immunosuppression are responsible for the poor prognosis of OSCC. Previous studies have shown that poly(ADP-ribose) polymerase (PARP)1 plays a key role in the pathogenesis of OSCC. Therefore, PARP1 may serve as an important research target for the potential treatment of OSCC. Here, we aimed to investigate the role of PARP1 in the tumorigenesis of OSCC and elucidate the key molecular mechanisms of its upstream and downstream regulation in vivo and in vitro. In human OSCC tissues and cells, Toll-like receptor (TLR)9 and PD-L1 were highly expressed and PARP1 was lowly expressed. Suppression of TLR9 remarkably repressed CAL27 and SCC9 cell proliferation, migration, and invasion. After coculture, we found that low expression of TLR9 inhibited PD-L1 expression and immune escape. In addition, TLR9 regulated PD-L1 expression through the PARP1/STAT3 pathway. PARP1 mediated the effects of TLR9 on OSCC cell proliferation, migration, and invasion and immune escape. Additionally, in vivo experiments further verified that TLR9 promoted tumor growth and immune escape by inhibiting PARP1. Collectively, TLR9 activation induced immunosuppression and tumorigenesis via PARP1/PD-L1 signaling pathway in OSCC, providing important insights for subsequent in-depth exploration of the mechanism of OSCC.NEW & NOTEWORTHY In this research, we took PARP1 as the key target to explore its regulatory effect on oral squamous cell carcinoma (OSCC). The key molecular mechanisms involved in its upstream and downstream regulation were elucidated in OSCC cell lines in vitro and tumor-bearing mice in vivo, combined with clinical OSCC tissues.

Microbiome analysis of saliva from oral squamous cell carcinoma (OSCC) patients and tobacco abusers with potential biomarkers for oral cancer screening

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and accounts for about 95% of all head and neck cancers with high mortality, usually at a late stage. Dysbiosis in the oral microbiome can lead to chronic inflammatory responses and may predispose to the development and progression of OSCC. Tobacco abuse plays an essential role in oral microbiome dysregulation and OSCC pathogenesis. We used 16S rRNA gene amplicon next-generation sequencing to examine microbial signatures unique to saliva from OSCC patients, tobacco abusers (TA) and controls (n = 10 for each group) to elucidate oral microbiome changes associated with tobacco abuse and OSCC. Overall, the oral microbiome compositions of class Betaproteobacteria and Epsilonproteobacteria, order Neisseriales, Burkholderiales and Campylobacterales, family Burkholderiaceae and Campylobacteraceae and genera Campylobacter and Leptotrichia revealed significant differences among OSCC patients, TA and control. Our preliminary pilot study not only serves as a basis for future studies with large sample size but also gives an indication of microbiome-based potential non-invasive biomarkers for early screening and monitoring of oral carcinogenesis transition due to tobacco abuse.

Association of oral bacteriome and oral squamous cell carcinoma

Oral cancer is the most common carcinoma of head and neck cancers. The majority of oral cancers are oral squamous cell carcinoma (OSCC). Among the various etiological factors, oral microbes—bacteria are also associated with pathogenesis of OSCC. But only few studies have been done associating the presence of oral bacteriome with OSCC. The main aim of this review is to focus on association of microbes with OSCC, the pathogenesis, variation in bacteriome profiling in different geographic conditions, their role in pathogenesis of OSCC, and different samples and methods that are used to study their association with habits and tumour node metastasis (TNM) staging. To conclude, the imbalance in the oral bacteriome could be considered an etiological factor for OSCC. Since the bacteriome profiling varies greatly with geographic location and even in an individual in different locations of the oral cavity, it advocates more research. The study on identifying bacteria associated with OSCC will also enable their use as diagnostic markers and preventive management of OSCC.

Emerging histological and serological biomarkers in oral squamous cell carcinoma: Applications in diagnosis, prognosis evaluation and personalized therapeutics (Review).

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and accounts for >90% of all oral cancers. Despite advances in diagnostic procedures and therapeutic interventions, overall survival has not improved significantly in recent decades, primarily due to late diagnosis, locoregional recurrence and treatment resistance. Identifying reliable biomarkers for early detection, prognosis evaluation and treatment response prediction is critical for improving clinical outcomes in patients with OSCC. In the present review, the prognostic and predictive utility of circulating biomarkers, such as circulating tumour cells, serological biomarkers and histological and genetic biomarkers, were explored in the context of OSCC. In addition, the potential role of immune checkpoints in the treatment of OSCC was highlighted and the rapidly evolving field of liquid biopsy and its potential to revolutionize diagnosis, prognosis evaluation and treatment were examined. The existing evidence for the clinical utility of these biomarkers was critically evaluated and the challenges and limitations associated with their introduction into routine clinical practice were addressed. In conclusion, the present review highlights the promising role of biomarkers in improving the current understanding of the pathogenesis of OSCC and offers potential avenues for improving patient care through personalized medicine approaches.