Oral Cancer Progression Research Articles

Jing-Si Herbal Tea attenuates oral cancer cell viability, migration, and invasion by regulating epithelial-to-mesenchymal transition and reactive oxygen species accumulation

Background/purposeOral cancer is the sixth most common cancer worldwide and can be life-threatening if not diagnosed and treated in its early stages. Jing-Si Herbal Tea (JSHT), containing eight traditional Chinese medicine-based herbs, is known to suppress the malignancy, growth, and metastasis of several tumor cells, including breast, lung, and colon cancer cells. However, the pharmacological effect of JSHT on oral cancer progression is still unclear. Materials and methodsIn this study, we evaluated the potential of JSHT to arrest the development of oral cancer via induction of cell death by reactive oxygen species (ROS) accumulation and inhibition of migration, invasion, and epithelial-to-mesenchymal transition (EMT). For this purpose, we employed the human tongue squamous cell carcinoma SAS cell line, which we treated with different JSHT concentrations for 24 h, and assessed cell viability, migration, and wound healing capabilities, together with western blotting for measuring expression levels of EMT markers. ResultsSurvival, migration/invasion ability, EMT, and ROS production in the SAS human tongue squamous carcinoma and FaDu human pharynx squamous cell carcinoma cell line were decreased by JSHT treatment via Lon protease-independent mechanisms. ConclusionThis study demonstrates that JSHT could be regarded as a candidate new supplement to existing anticancer therapies and an alternative, orally administered healthcare product for treating oral squamous cell carcinoma.

LINC00342 regulates the PI3K-AKT signaling pathway via the miR-149-5p/FGF11 axis and affects the progression of oral cancer

BackgroundA large number of long non-coding RNAs (lncRNAs) have been implicated in the progression of oral cancer (OC). This study aimed to investigate the role of a novel lncRNA, LINC00342, in OC and elucidate its molecular mechanism.MethodsDifferential expression of lncRNA/miRNA/mRNA was analyzed using the Gene Expression Omnibus database and validated with RT-qPCR. Additionally, the expression levels of these molecules in OC cells and their effects on cell viability and cell cycle were assessed using the Cell Counting Kit-8 and flow cytometry. RNA bindings was analyzed by dual luciferase, and Western blot was used to detect the activation of relevant pathways.ResultsThis study showed that, in contrast to miR-149-5p, the expression of LINC00342 and fibroblast growth factor 11 (FGF11) were upregulated in OC cells (LINC00342: 10.00 ± 1.06 (FaDu) and 3.55 ± 0.25 (CAL-27) vs 1.00 ± 0.07 (HOECs), P < 0.05; FGF11: 7.31 ± 0.33 (FaDu) and 3.43 ± 0.08 (CAL-27) vs 1.00 ± 0.10 (HOECs), P < 0.05). Dual-luciferase assays confirmed that LINC00342 bind to miR-149-5p in a direct targeting manner. Furthermore, inhibition of LINC00342 expression resulted in decreased proliferation rate (FaDu: 136.22 ± 22.10% vs 59.36 ± 8.98% (control), P < 0.05; CAL-27: 131.40 ± 11.58% vs 49.83 ± 11.19 (control), P < 0.05) and migration ability of OC cells, cell cycle arrest in G1 phase, and inhibition of PI3K-AKT signaling. Inhibition of miR-149-5p or overexpression of FGF11 reversed the effects of si-LINC00342.ConclusionsLINC00342 promotes PI3K-AKT signaling by activating FGF11 through adsorption of miR-149-5p, thereby regulating the progression of OC.

A bioinspired porous and electroactive reduced graphene oxide hydrogel based biosensing platform for efficient detection of tumor necrosis factor-α.

Oral cancer is one of the leading cancer types, which is frequently diagnosed at an advanced stage, giving patients a poor prognosis and fewer therapeutic choices. To address this gap, exploiting biosensors utilizing anti-biofouling hydrogels for early-stage oral cancer detection in non-invasive body fluids is gaining utter importance. Herein, we have demonstrated the fabrication of an innovative electrochemical immunosensor for the rapid, label-free, non-invasive, and affordable detection of tumor necrosis factor-α (TNF-α), a biomarker associated with oral cancer progression in artificial saliva samples. The gold screen-printed electrodes (gSPEs) are modified with a green synthesized porous and electroactive reduced graphene oxide (rGO) hydrogel utilizing L-cystine (L-cys) as both in situ reducing and surface functionalization agent, followed by covalent immobilization of anti-TNF-α and blocking of residual sites with bovine serum albumin (BSA) to fabricate the BSA/anti-TNF-α/L-cys_rGO hydrogel/gSPE immunosensing platform. The fabricated platform demonstrates excellent performance, with a low limit of detection of 1.20 pg mL-1, a broad linear range from 1 to 200 pg mL-1, and a high sensitivity of 2.10 μA pg-1 mL cm-2 carried out with differential pulse voltammetry (DPV) technique. Moreover, it exhibits specificity towards TNF-α, even in the presence of potential interferents and other cancer biomarkers. Besides, the biosensor showed good reproducibility and repeatability with a relative standard deviation (%RSD) of 5.11% and 1.85%, respectively. Thus, integrating the L-cys_rGO hydrogel in the immunosensor design offers enhanced performance, paving the way for its application in early-stage oral cancer diagnosis.

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.

Isolation and Identification Of Candida Albicans In Smokers With Epithelial Dysplasia And Squamous Cell Carcinoma: A Histopathological Correlation

Background:Greater adaptability of Candida to the host niche makes it the most common opportunistic pathogen. Its role as a commensal or pathogen in development of premalignancies and its progression to malignancies is of considerable debate. Present study was undertaken to determine the role of Candida albicans(CA)in progressionof oral cancer by isolation and identification by mycological methods in smokers without oral lesions and histopathologically diagnosed cases of epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC). Methodology:The study comprised of 120 cases that included study group of 40 smokers with oral lesions, 40 smokers without oral lesions and 40 non-smokers as control group. Clinical examination was followed by oral rinse sample collection and biopsy for histopathological confirmation. Sedimented oral rinse was inoculated on Sabouraud’s dextrose agar (SDA). Isolated Candida colony after identification with Gram stain was subjected to germ tube and chlamydospore formation test for confirmation of CA. The data was statistically analysed using chi square test. Results:Colonisation of CA was 52.5% in the study group and 5% in the control group, was found to be statistically significant (p&lt;0.001).Association of CA in smokers with varying histopathologic grades of oral lesions showed no evidence of a correlation. However, positive correlation was found in OSCC (n=19, 95%) and showed statistical significance (p&lt;0.001). Conclusion:The present study showed an increase in colonization of CA in malignant lesions suggesting that CA in conjunction with tobacco usage may play a role in oral carcinogenesis.

Salivary cysteine levels as a potential biochemical indicator of oral cancer risk in tobacco consumers.

Aim: Oral cancer is the leading cause of mortality, with a survival rate of less than 5 years, and is predominantly influenced by tobacco mutagens. Invasive diagnostic methods hinder early detection of oral cancer biomarkers. The present study performed salivary biochemical analysis for early oral cancer screening in tobacco consumers.Materials & methods: Three study groups included healthy controls (n=25), tobacco users (n=25) and oral cancer patients (n=25). Salivary total protein, amylase, TNF-α and amino acid levels were evaluated using enzymatic tests, Enzyme linked Immunosorbent Assay (ELISA) and High-Performance Liquid Chromatography (HPLC).Results: Compared with healthy controls, salivary total protein and TNF-αlevels were significantly (p=0.04) higher in oral cancer patients. Salivary amylase levels were significantly lower in tobacco smokers (p=0.02) and higher in oral cancer patients (p=0.01). Interestingly, the amino acid cysteine concentration was significantly higher (p=0.02) in tobacco consumers (62.5±10) than in healthy controls (116.1±28).Conclusion: In high-risk populations, such as tobacco users, salivary biochemical analysis can serve as a promising noninvasive diagnostic method for early oral cancer screening. As a salivary biomarker, the amino acid cysteine exhibits potential as a means of detecting the progression of oral cancer in individuals who consume tobacco.

Unraveling the key role of chromatin structure in cancer development through epigenetic landscape characterization of oral cancer

Epigenetic alterations, such as those in chromatin structure and DNA methylation, have been extensively studied in a number of tumor types. But oral cancer, particularly oral adenocarcinoma, has received far less attention. Here, we combined laser-capture microdissection and muti-omics mini-bulk sequencing to systematically characterize the epigenetic landscape of oral cancer, including chromatin architecture, DNA methylation, H3K27me3 modification, and gene expression. In carcinogenesis, tumor cells exhibit reorganized chromatin spatial structures, including compromised compartment structures and altered gene-gene interaction networks. Notably, some structural alterations are observed in phenotypically non-malignant paracancerous but not in normal cells. We developed transformer models to identify the cancer propensity of individual genome loci, thereby determining the carcinogenic status of each sample. Insights into cancer epigenetic landscapes provide evidence that chromatin reorganization is an important hallmark of oral cancer progression, which is also linked with genomic alterations and DNA methylation reprogramming. In particular, regions of frequent copy number alternations in cancer cells are associated with strong spatial insulation in both cancer and normal samples. Aberrant methylation reprogramming in oral squamous cell carcinomas is closely related to chromatin structure and H3K27me3 signals, which are further influenced by intrinsic sequence properties. Our findings indicate that structural changes are both significant and conserved in two distinct types of oral cancer, closely linked to transcriptomic alterations and cancer development. Notably, the structural changes remain markedly evident in oral adenocarcinoma despite the considerably lower incidence of genomic copy number alterations and lesser extent of methylation alterations compared to squamous cell carcinoma. We expect that the comprehensive analysis of epigenetic reprogramming of different types and subtypes of primary oral tumors can provide additional guidance to the design of novel detection and therapy for oral cancer.

Genetic variants of interleukin-1α, interleukin-12β and matrix metalloproteinase-9 in oral cancer risk and progression

BackgroundCytokines and matrix metalloproteinases play an important role in inflammation and metastasis in the development of cancer. Single nucleotide polymorphisms in these genes may affect gene expression and protein activity and, therefore, may be associated with cancer predisposition. The study seeks to examine the correlation between single nucleotide polymorphisms in the cytokines (Interleukin-1α and Interleukin-12β) and Matrix metalloproteinase (MMP9) gene with oral cancer. The interplay of the genetic variants, Interleukin 1α -889 C/T (rs1800587), Interleukin 12β +1188A/B (rs3212227), and MMP9 R279Q (rs17576) with tobacco chewing and smoking habits is determined in patients with oral cancer and controls. The relationship between these genetic variations with the tumor size, lymph node involvement, and metastasis in oral cancer was studied. MethodCase-control research was implemented with a total of 150 participants, which includes 50 individuals who were diagnosed with oral cancer and 100 healthy volunteers. The study on Single Nucleotide Polymorphism (SNP) was performed using the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) technique. ResultsInterleukin-1α -889 C/T polymorphism was significantly associated with oral cancer. The heterozygous genotype (CT) IL-1α -899 C/T was most frequent in oral cancer patients with a p value of 0.000002 in the chi-square test with no node involvement or metastasis. No interaction with the smoking or tobacco chewing habit with the genotypes of any of the genes is observed. The genotype of the mutant (TT) was also significantly different among the two groups (p = 0.01, OR = 7.63, CI- 1.5–37.5). The distribution of the mutant RR genotype of MMP9 R279Q in oral cancer patients was statistically significant in comparison with healthy controls (p = 0.005, OR = 4.46, CI- 1.52–3.04). The genotypic variants of IL-12β +1188A/B were, however, not found to be associated with oral cancer risk. IL-1α-899 (CT) and MMP9R279Q (RR) genotypes were found to be significantly associated with tumor size. ConclusionThis finding indicates that the substitution of C to T at IL-1α-889 position and substitution of glutamine with arginine at amino acid position 279 in MMP9 due to single nucleotide polymorphism increases the risk of oral cancer. IL-12β +1188 polymorphism was not associated with oral cancer risk. Habit does not play any role in the interaction of these genes with oral cancer.

Combined miR-181a-5p and Ag Nanoparticles are Effective Against Oral Cancer in a Mouse Model.

Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy. We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved. The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity. Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.

Let-7 reduces the proliferation and migration of oral cancer cells via PI3K/AKT signaling pathway.

The involvement of let-7 in the occurrence and progression of various cancers has been well-documented. However, the precise molecular mechanisms underlying its impact on oral cancer development remain unclear. In this study, we aimed to elucidate the role of let-7 in oral cancer progression and investigate its underlying molecular mechanisms. The expression of let-7 and high mobility group A2 (HMGA2) mRNA was assessed using the quantitative reverse transcription polymerase chain reaction. Western blot analysis was employed to detect the expression of key proteins in the PI3K/AKT signaling pathway as well as HMGA2 protein levels. The targeting relationship between let-7 and HMGA2 was predicted through bioinformatics methods and confirmed via luciferase reporter gene assay. The effects of let-7 and HMGA2 on the functionality of oral cancer cells were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, Transwell assay, wound healing assay, and Annexin V/PI apoptosis assay. Additionally, the impact of let-7 on the growth of oral cancer cells in vivo was investigated by inducing subcutaneous tumor formation in nude mice. Let-7 effectively suppresses the proliferation, migration, and invasion of oral cancer cells by inhibiting the activation of the PI3K/AKT signaling pathway. HMGA2, a downstream target gene of let-7, exhibits high expression in oral cancer. However, overexpression of HMGA2 diminishes the inhibitory effects induced by let-7 overexpression on the proliferation, migration, and invasion of oral cancer cells. The occurrence and progression of oral cancer cells are inhibited by Let-7 through the downregulation of HMGA2, potentially mediated by the inhibition of PI3K/AKT signaling pathway activation.

A novel m6A reader RBFOX2 expression is increased in oral squamous cell carcinoma and promotes tumorigenesis

Background and ObjectiveOral squamous cell carcinoma (OSCC) is a significant global health concern due to its aggressive nature and poor prognosis. Recent research has highlighted the important role of RNA modifications in cancer biology, especially N6-methyladenosine (m6A) modifications, which are controlled by a complex interplay of m6A regulators. This study specifically investigates RBFOX2, a new m6A reader, and its involvement in OSCC. MethodsOur study primarily utilized OSCC tissue, adjacent normal tissue samples, OSCC cell lines, and normal healthy oral keratinocytes to validate RBFOX2 mRNA expression. Additionally, we used the TCGA-HNSCC dataset for large cohort analysis and clinicopathological characterization. Furthermore, we visualized the RBFOX2 network to identify the primary functions of the protein. ResultsOur research shows a noticeable increase in RBFOX2 expression in OSCC tissues compared to adjacent non-tumorous tissues, as determined by quantitative PCR and immunohistochemistry analyses. Functional pathway enrichment analysis revealed that RBFOX2 is involved in the receptor tyrosine kinase signaling pathway and the Hippo signaling pathway, which plays a critical role in oral cancer development and progression. Clinically, elevated RBFOX2 expression correlated with advanced tumor stages and poorer patient outcomes, demonstrating its prognostic value. These findings indicate that RBFOX2 acts as an oncogenic driver in OSCC as an m6A reader, facilitating the expression of m6A-modified oncogenes. ConclusionOur study identifies RBFOX2 as a critical player in OSCC pathogenesis and opens avenues for novel therapeutic strategies targeting the m6A regulatory machinery in this malignancy.

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.

Areca nut-induced metabolic reprogramming and M2 differentiation promote OPMD malignant transformation

BackgroundBetel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive.MethodsImmunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE.ResultsWe reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters.ConclusionOur study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells.

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.

Mast Cell Infiltration and Subtype Promote Malignant Transformation of Oral Precancer and Progression of Oral Cancer.

In this study, we investigated the role of mast cells (MC) in oral precancer and oral cancer and demonstrated that MCs are involved in oral cancer progression and may serve as a potential diagnostic and prognostic marker. It might improve the immunotherapeutic efficacy through developing targeted therapies against MCs.

Evaluation of Tumor-Associated Macrophages and Micro-Vessel Density in Verrucous Carcinoma and Squamous Cell Carcinoma of the Oral Cavity.

Tumor-associated macrophages (TAMs) are a crucial cellular component of human tumors, but their exact roles in tumor growth and angiogenesis during cancer progression are still subject to debate. The present study aimed to explore the impact of TAMs on tumor progression and angiogenesis in oral squamous cell carcinoma (OSCC) and oral verrucous carcinoma (OVC). For this cross-sectional study, 60 samples consisting of 40 OSCC and 20 OVC samples were chosen. Immunohistochemical staining was performed on the samples using anti-CD68 and anti-CD31 monoclonal antibodies to evaluate the frequency of TAMs and micro-vessel density (MVD), respectively. The data were analyzed using statistical software SPSS (v. 23) and through the independent samples Student t-test, one-way analysis of variance, and Pearson's correlation coefficient. The results of our study revealed that the mean number of TAMs and MVD were significantly greater in OSCC samples compared to OVC samples (P = 0.001) (P = 0.004). Also, the average number of TAMs and MVD increased in the high grade of OSCC; however, the correlation between both parameters and histopathological grades of OSCC was significant only for MVD. Our study found no significant correlation between TAMs and MVD (P = 0.005). Based on the results of our study, both TAMs and MVD were found to be significantly higher in OSCC samples compared to OVC samples. These findings suggest that the progression of oral cancer is associated with an increase in TAMs and vascular density. Additionally, the use of CD68 and CD31 markers may help in differentiating between these two types of tumors.

Single nucleotide polymorphisms: A paradigm in oral disease research

Background: A higher occurrence of oral cancer is observed in South Asian and Southeast Asian countries when compared with other countries in the world. Cancer, a disease with complex pathophysiology, has been linked to chronic inflammation. Inflammation has been considered an important component of tumor initiation and progression. This is supported by the fact that many cancers arise at the sites of chronic inflammation, but the exact mechanism by which inflammation influences cancer is unknown. Purpose: This review article correlates single nucleotide polymorphisms (SNPs), chronic inflammation, and oral cancer. The article emphasizes the critical role that SNPs play in oral cancer susceptibility, progression, and prognosis. This involves discussing the impact of specific SNPs on oral cancer risk and patient outcomes. Review: Gene polymorphism has been documented in the molecular pathogenesis of various cancers, including oral cancer, and SNPs are the most common form of gene polymorphism. Genetic variation has been documented in the molecular pathogenesis of various cancers, including oral cancer, and SNPs are the most common form of gene polymorphism. SNPs have been documented in inflammatory conditions as well as in various diseases. Conclusion: SNPs have phenotypic consequences and therefore can serve as genetic fingerprints. The upregulation or downregulation of genes is able to drive oral carcinogenesis.

BIOLOGICAL AND PROGNOSTIC IMPORTANCE OF CYTOKINES IN ORAL CANCER

Epidemiological data indicate high rates of morbidity and mortality of oral mucosal cancer worldwide. At the same time, even visual accessibility does not allow detecting oral cancer in the early stages. The purpose of the study. Assessment of the involvement of cytokines in the development and progression of oral cancer. Materials and methods. The search for publications was carried out in the databases of the RSCI, PubMed, Scopus 2019-2023 years for the following queries: cancer of the oral mucosa; potentially malignant diseases of the oral cavity; precancerous diseases of the oral cavity, inflammation and cancer, cytokines, saliva cytokines, serum cytokines. Results. It is now recognized that under the influence of inflammation, neoplastic and stromal cells interact and control tumor evolution by producing cytokines. Modern studies demonstrate the important role of cytokines such as TNF-α, IL-8, IL-6, IL-1β in the development and progression of oral cancer. A review of the conducted studies indicates that cytokines released by tumor cells of oral cancer, as well as the tumor microenvironment, contribute to cell proliferation, survival, and migration of tumor cells of this localization, although they activate immune cells, contributing to the modulation of the antitumor immune response. Hyperproduction of cytokines, registered at the local and systemic levels, appears to be a consequence of dysregulation of proliferative processes and at the same time one of the causes of tumor spread. Conclusion. Modern research demonstrates the important role of various cytokines in the development and progression of cancer of the oral mucosa. In this regard, therapeutic approaches that limit their growthstimulating activity should be considered.

TUSC3, p53 and p21 genetic association with development of oral submucous fibrosis and oral squamous cell carcinoma among addictive tobacco chewers of Pakistan

BackgroundThis study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy’s development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF.MethodsIn this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping.ResultsThe study’s patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development.ConclusionsNotably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.

Assessing DNA methylation of ATG 5 and MAP1LC3Av1 gene in oral squamous cell carcinoma and oral leukoplakia- a cross sectional study

BackgroundThe progression and pathogenesis of oral cancer is greatly impacted by epigenetic modifications, such as DNA methylation. Autophagy, is an adaptive mechanism used to maintain the survival and integrity of cells. Oral squamous cell carcinoma is linked to a number of autophagy indicators, although it is yet unknown if DNA methylation of autophagy-related genes promotes the development of oral leukoplakia (OL), oral squamous cell carcinoma (OSCC). AimOur study was aimed to assess, compare and evaluate the DNA methylation of ATG5 and MAP1LC3Av1 genes in oral leukoplakia, oral squamous cell carcinoma. Materials and methodsThis cross-sectional study was designed with sample size of 48 tissues which was clinically and histopathologically diagnosed as OL, OSCC and normal tissue. The samples were divided into three groups (Group A, Group B, and Group C; (n = 16 each). Following histopathological confirmation, the tissue was stored in the RNA reagent, then subjected to DNA extraction, methylation-sensitive polymerase chain reaction (MS-PCR). DNA methylation of the ATG5 and MAP1LC3Av1 genes were assessed. ResultsShapiro-Wilk and Kolmogorov-Smirnov tests showed that the values were normally distributed. Both the ATG5 and MAP1LC3Av1 genes were methylated in OSCC, OL tissues compared to normal tissues. A statistically significant results was seen among the three study groups. ConclusionA significant difference was noted in the hypermethylation status of the promoter regions of the ATG5 and MAP1LC3Av1 genes. This provides some insight into their crucial role in the development of tumors. Future research with larger sample is needed to assess its potential clinical implications in oral carcinoma.