Oral Squamous Cell Carcinoma Samples Research Articles

FGFR1 Gene Expression and its Relationship with Sociodemographic and Clinicopathological Indices in Oral Squamous Cell Carcinoma

Introduction: A better prognosis has resulted from the use of molecular techniques in cancer diagnosis. The FGFR family of genes is one of the major gene families involved in the carcinogenic pathways of different malignancies. Tumorigenesis, uncontrolled cell proliferation, and a number of pathologic diseases are linked to improper FGFR activation. The family of genes known as FGFRs encodes cell surface membrane receptors with tyrosine kinases.The development of oral squamous cell carcinoma (OSCC) may be significantly influenced by fibroblast growth factor receptor 1 (FGFR1). Analyzing these elements' expression patterns may provide fresh perspectives on illness management strategies including genetic mediated target therapy. Objectives: In order to improve care and prevent future difficulties from oral squamous cell carcinoma (OSCC), the current study sought to assess the expression of FGFR1 genes in OSCC tumors as a result of the discovery of biomarkers and early diagnosis. Methods:In order to assess the expression of FGFR1 genes in 16 OSCC samples, 16 normal specimens from the same sample, free from cancer margin and 4 control samples from other patient free from cancer, the Oral and Maxillofacial Surgery DepartmentatDental Unit of Rajshahi Medical College Hospital was collected. Trizol and the appropriate kits were used for RNA extraction and cDNA synthesis. Real-time PCR was used to assess the FGFR1 gene's expression following the construction of a specific primer set in order to find and validate molecular biomarkers. The data is analyzed using the ANOVA and independent t-test. Statistics were shown to be significant when P<0.05. Results:According to the findings, there are notable variations in the expression of the FGFR1 gene between tumor and normal or control tissues (P < 0.001). Patients over 60 are more likely to have OSCC, and the majority of them smoke 8. Retromolar trigon 8 is the most frequent location, and the majority of them are in stages III and IV. The FGFR1 gene expression does not significantly differ according on a patient's age, gender, religion and behavior, including whether they smoke, drink, or chew paan. It also does not differ depending on the tumor's location, stages and grade. Conclusions: The FGFR1 gene was often expressed differently in cancerous and control tissues, confirming the gene's involvement in OSCC. The expression of FGFR1 is not correlated with factors such as gender, age, history of smoking, alcohol intake, chewing paan, tumor site, degree of differentiation, or TNM stage. The current investigation demonstrated the critical function of the investigated gene in the diagnosis of OSCC. To verify this, though, more research is required. TAJ 2023; 36: No-2: 155-162

Porphyromonas gingivalis promotes the progression of oral squamous cell carcinoma by stimulating the release of neutrophil extracellular traps in the tumor immune microenvironment.

The aim of this study was to investigate the impact of Porphyromonas gingivalis (P. gingivalis) on the progression of oral squamous cell carcinoma (OSCC) through neutrophil extracellular traps (NETs) in the tumor immune microenvironment. The expression of NETs-related markers was identified through immunohistochemistry, immunofluorescence, and Western blotting in different clinical stages of OSCC samples. The relationship between NETs-related markers and clinicopathological characteristics in 180 samples was analyzed using immunohistochemistry data. Furthermore, the ability to predict the prognosis of OSCC patients was determined by ROC curve analysis and survival analysis. The effect of P. gingivalis on the release of NETs was identified through immunofluorescence and immunohistochemistry, both in vitro and in vivo. CAL27 and SCC25 cell lines were subjected to NETs stimulation to elucidate the influence of NETs on various cellular processes, including cell proliferation, migration, invasion, and metastasis in vitro. Furthermore, the impact of NETs on the growth and metastatic potential of OSCC was assessed using in vivo models involving tumor-bearing mice and tumor metastasis mouse models. Immunochemistry analysis revealed a significant correlation between the NETs-related markers and clinical stage, living status as well as TN stage. P. gingivalis has demonstrated its ability to effectively induce the release of NETs both in vivo and in vitro. NETs have the potential to facilitate cell migration, invasion, and colony formation. Moreover, in vivo experiments have demonstrated that NETs play a pivotal role in promoting tumor metastasis. High expression of NETs-related markers demonstrates a strong correlation with the progression of OSCC. Inhibition of the NETs release process stimulated by P. gingivalis and targeted NETs could potentially open up a novel avenue in the field of immunotherapy for patients afflicted with OSCC.

MicroRNA-21 as a biomarker in terminal stage oral squamous cell carcinoma (OSCC) in the South Indian population

ObjectiveMicro RNA-21(miR-21) earlier identified as high amount in different types of cancer. They are non-coding sequences with limited no of nucleotides and play important role in regulation of genes. Predicting the miR-21 levels could act as biomarkers for Oral Squamous Cell Carcinoma (OSCC). OSCC include every cancer found in the oropharynx and oral cavity. The current study retrieved mature sequences of miRNA from database- NCBI and used to find miRNA from OSCC. Its coming among the list of most prevalent malignancy in world, especially in India. This paper primarily focuses on miR-21 expression analysis as a biomarker of oscc in the South Indian population. Materials and methodsmiR-21 secondary structure is predicted using Bioinformatics tools from OSCC. Sequence was extracted from NCBI 25 OSCC samples and adjacent normal tissues were collected, and RNA were extracted, quantified, and reverse transcribed after doing histopathological analysis in cancer tissues. Expression of miR-21 done using qRT-PCR from the cDNA obtained. Utilizing statistical software, the relationship between the expression of miR-21 and the clinicopathological characteristics of OSCC was examined. Level of expression of genes in both cancer cells and normal cells are also analysed using graphical method. ResultmiR-21 secondary structure is predicted by applying mature sequence of miRNA. The values obtained by statistical analysis showed expression of miR-21 is increased in oscc samples compared to normal cells. ConclusionThus miR-21 is a potential biomarker associated with OSCC. Study also elucidated positive correlation between miR-21 in oscc samples.

Autophagy indicators in oral squamous cell carcinoma

Autophagy plays an important role in maintaining cellular homeostasis. Dysregulation of autophagy has been linked to a number of diseases, including cancer. We retrospectively evaluated immunohistochemical expression of the autophagy markers LC3B and p62 and the autophagy regulator mTOR as an indicator of autophagy in 100 surgically resected primary oral squamous cell carcinoma (OSCC) samples and sought associations with various clinicopathological factors. The expression of all three proteins was significantly higher in malignant squamous cells than in benign squamous cells in the free mucosal margin adjacent to the OSCC. Male sex, higher tumour (T) stage, node (N) stage and tumour, node, metastasis (TNM) stage were significantly associated with high marker expression; age and histological grade showed no significant association. LC3B, p62 and mTOR expression were positively correlated with one another in OSCCs, and the correlation was significant for LC3B and mTOR as well as for LC3B and p62. Disease-free survival showed an inverse correlation with high mTOR expression. Our data suggest that autophagy inhibitors and mTOR inhibitors may have a therapeutic role in the treatment of OSCCs.

Investigating the Association Between Fusobacterium nucleatum and Oral Squamous Cell Carcinoma: A Pilot Case-Control Study on Tissue Samples.

Background Fusobacterium nucleatum (F. nucleatum)has been increasingly linked to oral squamous cell carcinoma (OSCC), prompting this study to explore its presence using polymerase chain reaction (PCR) and evaluate its clinical significance. Methods In this pilot case-control study, 12 OSCC tissue samples and 12 non-cancerous oral mucosal tissue samples were analyzed. Total RNA extraction and complementary DNA (cDNA) synthesis were performed using Trizol-based methods, followed by PCR amplification and gel electrophoresis. The clinical characteristics of participants and PCR results were recorded. Results Among the OSCC tissue samples, three out of 12 tested positive forF. nucleatum,while none of the control samples showed its presence. The detection rate ofF. nucleatumin OSCC was 25%. Gel analysis confirmed specific amplicon amplification, and ImageJ software enabled copy number quantification. Discussion Our findings support previous research indicating a potential association betweenF. nucleatumand OSCC. Understanding the etiological significance ofF. nucleatumin OSCC has clinical implications, including early detection, risk stratification, and prognostication. However, the limited sample size and the need for further research to elucidate underlying mechanisms are acknowledged. Conclusion This pilot study provides initial evidence ofF. nucleatum'spresence in a subset of OSCC samples, supporting its potential association with oral cancer. DetectingF. nucleatumin OSCC tissues holds promise for future research and clinical applications as a diagnostic and prognostic biomarker. Understanding its role in oral carcinogenesis will facilitate the development of targeted therapeutic strategies. Larger studies are warranted to validate these findings and investigate the precise mechanisms involved.

Unidirectional alteration of methylation and hydroxymethylation at the promoters and differential gene expression in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Although overall losses of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been previously observed, a genome-wide, single-base-resolution, and simultaneous mapping of 5mC and 5hmC in OSCC is still unaccomplished. Similarly, the mechanism of how 5mC and 5hmC collectively lead to abnormal gene expression in OSCC is largely unexplored. Using parallel whole-genome bisulfite sequencing (WGBS) and whole-genome oxidative bisulfite sequencing (oxWGBS), we characterized 5mC- and 5hmC-profiles at single-nucleotide resolution in paired primary OSCC samples and their normal adjacent tissues (NATs). We also analyzed the effect of 5mC- and 5hmC-modifications on differential gene expression in OSCC using multi-omics analysis. Results: An overall reduction of both 5mC and 5hmC in various genomic regions have been observed in OSCC samples. At promoter regions, a total of 6,921 differentially methylated regions and 1,024 differentially hydroxymethylated regions were identified in OSCC. Interestingly, compared to bidirectional modification with 5mC and 5hmC, unidirectional modification with 5mC and 5hmC at the promoters is associated with bigger change in the gene expression. Additionally, genes bearing unidirectional modification with 5mC and 5hmC at the promoters are enriched in signaling pathways like cell proliferation, cell differentiation, and receptor tyrosine kinase pathway that are essential for the tumorigenesis. Finally, the grouped expression signature of top 20 genes bearing promoter-unidirectional-modification with 5mC and 5hmC tends to correlate with the clinical outcome of certain subtypes of head and neck squamous cell carcinoma. Conclusion: Using parallel WGBS and oxWGBS analyses, we observed an overall reduction of 5mC- and 5hmC-modifications at various genomic regions in OSCC. Unidirectional modification with 5mC and 5hmC at the promoters is associated with enhanced changes in gene expression in OSCC tissues. Furthermore, such differentially expressed genes bearing unidirectional modifications with 5mC and 5hmC at the promoters might have clinical relevance to the outcome of OSCC.

Expression profiling of signal transducer and activator of transcription3 in oral squamous cell carcinoma in south Indian population.

Oral squamous cell carcinoma (OSCC) is widely acknowledged as the most prevalent form of oral malignancy. The annual identification of approximately 540,000 new cases of OSCC highlights its significant impact. The survival rate beyond 5 years postsurgery remains low. The role of signal transducer and activator of transcription3 (STAT3), a signaling protein involved in various cellular processes, has garnered attention. Aberrant activation of STAT3 has been implicated in OSCC progression and aggressiveness. Understanding the impact of STAT3 dysregulation on OSCC outcomes could provide valuable insights for developing targeted therapies. The aim of this study was to evaluate and compare the expression levels of STAT3 in OSCC and normal tissues of the same patients. The expression levels of STAT3 in 63 OSCC samples were detected by qRT-PCR and compared to patient-matched-non-tumor oral tissues. Data were normalized to internal controls, and fold change in STAT3 expression was calculated using the ∆∆Ct method. Correlations between expression level and clinicopathologic characteristics like staging and grading of OSCC samples were also analyzed. Our findings demonstrated that STAT3 expression was significantly upregulated (P<0.0001) in OSCC patients compared to normal control tissue. Furthermore, we also observed a positive correlation between elevated STAT3 expression and higher OSCC histological grades when compared to the normal tissue. Well differentiated OSCC showed a slightly lower expression compared to the other two grades. Our results support the involvement of STAT3 in OSCC tumorigenesis. We propose that STAT3 might be used as a potential biomarker for OSCC. Further investigations are warranted to elucidate the mechanistic basis for the observed associations and to explore STAT3's potential as a therapeutic target in OSCC.

MiRNA Associated With Glucose Transporters in Oral Squamous Cell Carcinoma: A Systematic Review.

Oral squamous cell carcinoma (OSCC) is a malignancy of the oral cavity with poor prognosis. Dysregulation in glycolytic pathways involving glucose transporters (GLUT) has been implicated in poor prognosis. Furthermore, GLUT expression in cancer cells is regulated by several miRNAs. However, there is a lack of data about miRNA involved in the regulation of GLUT in OSCC. The objective is to evaluate the role of miRNA in the regulation of GLUT in OSCC. Data sources include PubMed (MEDLINE), Scopus, and Web of Science. Studies evaluating the miRNA involved or associated with the regulation of GLUT in OSCC were included in the systematic review. Data pertaining to GLUT and associated miRNA expression were extracted from studies. Qualitative assessment was carried out for GLUT and miRNA. The Newcastle-Ottawa Scale was used for quality assessment. Ten study articles were included after analyzing 4675 papers. These studies evaluated the GLUT and miRNA expression between healthy and OSCC samples. There are variable expression patterns of GLUT in OSCC. Furthermore, it was dependent on miRNA. The GLUT1 and GLUT-3 were detected more frequently in OSCC, while no study reveals the expression of GLUT2, GLUT4, GLUT7, GLUT8, GLUT13, SGLT1, and SGLT2 with miRNA regulation. However, there was insufficient evidence on specific miRNA linked to GLUT1 or GLUT3 expression. There is evidence of the role of miRNA in the regulation of GLUT especially GLUT1 and GLUT3 in OSCC; however, a specific relation to miRNA was understudied.In the future, studies exploring a clearer understanding of the association between miRNA and the GLUT metabolic pathway in relation to OSCC are warranted. Furthermore, association of miRNA and GLUT with progression of disease, disease resistance, and prognosis is assessed for better treatment outcomes.

GAD1-mediated GABA elicits aggressive characteristics of human oral cancer cells

Studies suggest that the expression of glutamate decarboxylase 1 (GAD1), γ-aminobutyric acid (GABA), and GABA receptors are involved in tumor progression. However, the underlying mechanisms of high expression and potential functions of GAD1 and GABA in oral squamous cell carcinoma (OSCC) are not known. In this study, we found that the expressions of GAD1 and GABA were considerably increased in OSCC samples, which were closely associated with clinical stage and lymph node metastasis. The knockdown of GAD1 expression significantly inhibited the proliferation, migration and invasion abilities of OSCC cells by reducing the expression of GABA-mediated GABAB receptors, which could be reversed by exogenous GABA, but did not cause excessive OSCC cell proliferation. And GABA secreted by OSCC cells promoted M2 macrophage polarization for inhibiting anti-tumor immunity by activating GABBR1/ERK/Ca2+. In addition, GABA/GABABR promoted the proliferation and progression of OSCC xenograft tumor. Altogether, our results showed that GAD1 synthetized GABA to promote the malignant progression of OSCC and limits the anti-tumor immunity of macrophages, thereby targeting GABA can be a novel strategy for treating OSCC.

Hsa-miR-26a-5p improves OSCC sensitivity to ferroptosis by inhibiting SLC7A11

ObjectiveSLC7A11 plays a crucial role in ferroptosis and is upregulated in oral squamous cell carcinoma (OSCC) samples. This study mainly aimed to elucidate the association of SLC7A11 with ferroptosis in OSCC and analyze its upstream regulatory mechanism. DesignThe expression of SLC7A11 in OSCC and paracancerous tissues was detected. After administration of different concentrations of erastin to OSCC cells, cell viability was examined by MTT, and changes in GSH, MDA and Fe2+ concentrations were determined. Then, mitochondrial changes were examined by transmission electron microscopy. Bioinformatics analysis was performed to predict the upstream regulatory miRNA of SLC7A11, and the interaction between miR-26a and SLC7A11 was confirmed by a dual luciferase reporter gene. The effect of miR-26a mimics on ferroptosis resistance was also examined. ResultsSLC7A11 expression was upregulated in both OSCC patients and cells, with high SLC7A11 expression levels in SCC-9 cells with an IC50 = 69.75 μM for erastin and low SLC7A11 expression levels in SCC-4 cells with an IC50 = 8.463 μM for erastin. SCC-9 exhibited a higher level of ferroptosis resistance than SCC-4. miR-26a-5p expression was downregulated in both OSCC patients and cells. A dual luciferase reporter assay confirmed that miR-26a-5p targets binding to the SLC7A11 3′UTR. Transfection of the miR-26a mimic significantly inhibited the viability of OSCC cells and promoted erastin-induced cellular ferroptosis. Transfection of miR-26a inhibitor gave the opposite result. Overexpression of SLC7A11 significantly reversed miR-26a mimic ferroptosis induction. ConclusionmiR-26a-5p can exert OSCC inhibitory effects by regulating SLC7A11 and promote ferroptosis in OSCC cells by inhibiting SLC7A11.

Construction of a New Prognostic Model for Oral Squamous Cell Carcinoma Based on Telomere-Related Genes

We investigated the prognostic value of telomere-related genes in oral squamous cell carcinoma (OSCC) using the TCGA-OSCC dataset and GSE41613 external validation set. We identified differentially expressed genes (DEGs) between OSCC and control samples and intersected them with telomere-related genes. Three risk model genes (IGF2BP2, EIF5A2, and PLOD2) were obtained through Cox and LASSO analyses. A risk model was constructed based on the expression of these genes. The OSCC samples were divided into high and low-risk groups using the median risk score. Univariate and multivariate Cox analyses identified risk score and age as independent prognostic factors. Gene set enrichment analysis revealed enrichment in chemical stimulus and appendage development pathways. We constructed a transcription factor (TF)-mRNA network involving two mRNAs (EIF5A2, PLOD2) and 17 TFs, including STAT1-EIF5A2 and TEAD1-EIF5A2. Immune-infiltration analysis showed significant differences in the abundance of 11 immune cells between the high and low-risk groups, including T cells CD8, activated mast cells, and macrophages M0. Our findings contribute to the development of a telomere-related risk model (including IGF2BP2, EIF5A2, and PLOD2) for predicting the prognosis of OSCC, providing new insights for further studies in this area.

THBS1-Mediated Degradation of Collagen via the PI3K/AKT Pathway Facilitates the Metastasis and Poor Prognosis of OSCC.

Oral squamous cell carcinoma (OSCC) is a prevalent form of malignant tumor, characterized by a persistently high incidence and mortality rate. The extracellular matrix (ECM) plays a crucial role in the initiation, progression, and diverse biological behaviors of OSCC, facilitated by mechanisms such as providing structural support, promoting cell migration and invasion, regulating cell morphology, and modulating signal transduction. This study investigated the involvement of ECM-related genes, particularly THBS1, in the prognosis and cellular behavior of OSCC. The analysis of ECM-related gene data from OSCC samples identified 165 differentially expressed genes forming two clusters with distinct prognostic outcomes. Seventeen ECM-related genes showed a significant correlation with survival. Experimental methods were employed to demonstrate the impact of THBS1 on proliferation, migration, invasion, and ECM degradation in OSCC cells. A risk-prediction model utilizing four differentially prognostic genes demonstrated significant predictive value in overall survival. THBS1 exhibited enrichment of the PI3K/AKT pathway, indicating its potential role in modulating OSCC. In conclusion, this study observed and verified that ECM-related genes, particularly THBS1, have the potential to influence the prognosis, biological behavior, and immunotherapy of OSCC. These findings hold significant implications for enhancing survival outcomes and providing guidance for precise treatment of OSCC.

Analysis of Genes Related to Invadopodia Formation and CTTN in Oral Squamous Cell Carcinoma-A Systematic Gene Expression Analysis.

Successful treatment for any type of carcinoma largely depends on understanding the patterns of invasion and migration. For oral squamous cell carcinoma (OSCC), these processes are not entirely understood as of now. Invadopodia and podosomes, called invadosomes, play an important role in cancer cell invasion and migration. Previous research has established that cortactin (CTTN) is a major inducer of invadosome formation. However, less is known about the expression patterns of CTTN and other genes related to it or invadopodia formation in OSCC during tumor progression in particular. In this study, gene expression patterns of CTTN and various genes (n = 36) associated with invadopodia formation were analyzed to reveal relevant expression patterns and give a comprehensive overview of them. The genes were analyzed from a whole genome dataset of 83 OSCC samples relating to tumor size, grading, lymph node status, and UICC (Union for Internatioanl Cancer Control). The data revealed significant overexpression of 18 genes, most notably CTTN, SRC (SRC proto-onocogene, non-receptor tyrosine kinase), EGFR (epidermal growth factor receptor), SYK (spleen associated tyrosine kinase), WASL (WASP like actin nucleation promotion factor), and ARPC2 (arrestin beta 1) due to their significant correlation with further tumor parameters. This study is one of the first to summarize the expression patterns of CTTN and related genes in a complex group of OSCC samples.

Role of Stromal Fibroblast–Induced WNT7A Associated with Cancer Cell Migration Through the AKT/CLDN1 Signaling Axis in Oral Squamous Cell Carcinoma

Wnt signaling plays a crucial role in the progression of various cancers, including oral squamous cell carcinoma (OSCC). However, the tumor microenvironment (TME) regulating Wnt signaling has not yet been fully elucidated. In this study, we investigated whether cancer-associated fibroblasts (CAFs), the primary components of the TME, activate Wnt signaling and promote tumor progression in OSCC. We conducted a Transwell coculture assay using human OSCC cell lines and normal human dermal fibroblasts (NHDFs). NHDFs stimulated WNT7A expression in several OSCC cell lines, especially HO-1-N-1 and HSC-5. An immunohistochemical study using 122 human OSCC samples indicated that high WNT7A expression in tumor cells was significantly associated with invasion depth and poor prognosis. Moreover, WNT7A expression in OSCC cells was positively correlated with α–smooth muscle actin expression in CAFs. WNT7A knockdown in OSCC cells demonstrated that OSCC cells cocultured with NHDFs significantly promoted tumor cell migration and invasion, which was dependent on WNT7A expression in OSCC cells. We also isolated HSC-5 cells from the coculture and conducted microarray analysis to investigate the factors that promote tumor progression induced by WNT7A. Among the various differentially expressed genes, we identified a downregulated gene encoding CLDN1 and confirmed that WNT7A negatively regulated CLDN1 expression in OSCC cells and CLDN1 knockdown in OSCC cells promoted their migration. Phosphokinase array analysis showed that WNT7A activates protein kinase B (AKT) phosphorylation. Activating AKT signaling using the SC79 agonist induced CLDN1 downregulation in OSCC cells. In the coculture assay, the AKT inhibitor MK2206 significantly recovered CLDN1 expression downregulated by WNT7A, resulting in OSCC cell migration suppression. These results suggest that CAFs stimulate OSCC cells to produce WNT7A, following CLDN1 expression downregulation by activating AKT signaling, promoting cancer cell migration. These findings highlight the importance of molecular therapies targeting the TME in OSCC.

TP53 gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma

BackgroundTP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. Somatic TP53 mutations occur in high frequencies in head and neck cancers, including...

Expression levels of microRNA-7110 in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, and it is responsible for more than 95% of head and neck cancers. Despite advancements in research and treatment, patient's survival has not significantly increased in recent years. On the other hand, microRNAs (miRNAs) are a major class of small non-coding RNAs that regulate gene expression of the target mRNAs. Thus, understanding the mechanisms behind OSCC formation and progression may lead to the identification of potential diagnostic biomarkers and therapeutic molecules for the treatment of OSCC. The aim of the current study was to analyze expression levels of miR-7110 in OSCC tissues and adjacent normal tissues as it could provide insights into its potential role in OSCC development or progression as a valuable biomarker. A total of 20 OSCC and adjacent normal tissues were collected from the Department of Oral and Maxillofacial Surgery, Saveetha Dental College and Hospitals (Chennai, India). The tissues were processed for hematoxylin and eosin staining and expression studies. The data were shown as mean±standard deviation and P<0.05 was considered statistically significant. Our histopathological observations revealed an invasive malignant epithelial neoplasm with malignant epithelial cells exhibiting features of severe epithelial dysplasia invading the connective tissue stroma as islands, strands and cords with varying degrees of differentiation. Our results have also revealed that the expression levels of miR-7110 were found to be significantly higher in OSCC samples when compared to the normal tissue. We can preliminarily conclude that based on the increased expression of miR-7110 in OSCC tissue samples, they can be used as an early diagnostic or prognostic biomarker and/or a therapeutic target for the treatment of OSCC even though more focused research in that direction is needed.

Prognostic model based on telomere-related genes predicts the risk of oral squamous cell carcinoma

BackgroundThis study investigated a potential prognostic model based on telomere-related genes (TRGs) for the clinical prediction of oral squamous cell carcinoma (OSCC).MethodsGene expression data and associated clinical phenotypes were obtained from online databases. Differentially expressed (DE)-TRGs were identified between OSCC and normal samples, followed by protein-protein interaction and enrichment analyses. Subsequently, the prognostic genes explored based on the DE-TRGs and survival data were applied in the establishment of the current prognostic model, and an integrated analysis was performed between high- and low-risk groups using a prognostic model. The expression of certain prognostic genes identified in the present study was validated using qPCR analysis and/or western blot in OSCC cell lines and clinical samples.Results169 DE-TRGs were identified between the OSCC samples and controls. DE-TRGs are mainly involved in functions such as hypoxia response and pathways such as the cell cycle. Eight TRGs (CCNB1, PDK4, PLOD2, RACGAP1, MET, PLK1, KPNA2, and CCNA2) associated with OSCC survival and prognosis were used to construct a prognostic model. qPCR analysis and western blot showed that most of the eight prognostic genes were consistent with the current bioinformatics results. Analysis of the high- and low-risk groups for OSCC determined by the prognostic model showed that the current prognostic model was reliable.ConclusionsA novel prognostic model for OSCC was constructed by TRGs. PLOD2 and APLK1 may participate in the progression of OSCC via responses to hypoxia and cell cycle pathways, respectively. TRGs, including KPNA2 and CCNA2, may serve as novel prognostic biomarkers for OSCC.

Aldehyde Dehydrogenase: An Off-Label Marker of Endothelial Activation in Oral Squamous Cell Carcinoma.

The vascular endothelial (VE) expression of aldehyde dehydrogenase (ALDH) 1/2 family in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cases has not been studied so far. The aim of this study was to illustrate the "off-label" endothelial expression of cancer stem cell (CSC) biomarker, ALDH1/2, adjacent to oral potentially malignant and malignant lesions in order to shed some light on the mechanisms leading to oral carcinogenesis. Materials and methods: The expression of CSC protein-biomarker ALDH1/2 was detected through immunohistochemistry (IHC) in 30 paraffin-embedded samples of OL and 21 samples of OSCC compared to five samples of normal oral mucosa. Statistical analysis was done using SPSS, Pearson Chi-square, and Fischer's exact test. The significance level was set at 0.05 (p≤ 0.05). Results: In oral mucosal vessels, ALDH1/2 was not expressed. It was expressed significantly more in the vessels of OSCCs compared to the OLs (Fisher's exact test, p-value= 0,001). However, when endothelial expression of ALDH1/2 in the vasculature of OLs was compared with that of the normal oral mucosa, no significant change was noticed (Fisher's exact test, p-value=1.000). Discussion: The IHC VE expression of ALDH1/2 in OSCCvasculature but not in OL indicates a possible significantly stronger activation of endothelial cells during carcinogenesis, which could be an indicator of the role of inflammation in the development of field cancerization and of prognostic value for (vascular/lymphatic) metastasis.

Gene expression analysis of microRNA-1285 in the South Indian oral squamous cell carcinoma population.

Oral squamous cell carcinoma (OSCC) is the most common oral malignant tumor, which has poor prognosis. The traditional investigative modality is invasive biopsy which is the gold standard for diagnosis. In recent years, alternative methods like non-invasive biomarkers have been studied for their potential role in early diagnosis and prognosis. Among them, microRNAs (miRNAs or miRs) are short non-coding RNAs that regulate gene expression in various diseases, including OSCC. Several miRNAs are being researched as non-invasive biomarkers as well as novel therapeutic targets in the treatment of OSCC. MiR expression can be upregulated or downregulated in OSCC. Among the reported miRNAs, miR-1285 is an important miRNA found to be involved in OSCC. The aim of the current study was to quantify the levels of miR-1285 in OSCC samples and to validate their potential role as biomarkers for OSCC detection. Sixteen samples of cancer tissue and normal tissue were evaluated from a total of 25 patients, in the study, conducted in the Department of Oral and Maxillofacial Surgery. The tissues were processed for H&E staining and gene expression analysis of miR-1285. The samples were collected after proper informed consent from the patients. Total RNA isolated was reverse transcribed into cDNA which was used in the gene expression analysis using qRT-PCR. The histopathological examination confirmed the OSCC cases and the gene expression analysis revealed that miR-1285 was significantly downregulated in OSCC tissues. Since miR-1285 showed significant difference between the OSCC and normal tissues it could be postulated as a potential biomarker and therapeutic target for OSCC. Further in-vitro and in-vivo studies could validate their functional role in OSCC.

A2b and A3 adenosine receptors may act as promotive and prognostic factors in oral squamous cell carcinoma

This study aimed to examine the expression and potential effects of adenosine receptors in oral squamous cell carcinoma (OSCC).Data on mRNA expression of adenosine receptors in OSCC samples were collected from The Cancer Genome Atlas database. Adenosine-regulated signaling pathways and biological processes were investigated via immune cell infiltration analysis, bioinformatics analysis, and immunohistochemistry.Overexpression of A2bR and A3R was significantly correlated with the prognosis of OSCC (P < 0.05). A3R expression in OSCC patients was significantly and positively correlated with the infiltration of six types of immune cells: B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and myeloid dendritic cells. A2bR expression weakly and negatively correlated with B-cell infiltration only. The expression of A2bR in OSCC was positively correlated with E-cadherin and PCNA, while the expression of A3R was positively correlated with that of cleaved caspase-3.Within the limitations of the study it seems that the overexpression of A2bR and A3R results in the poor prognosis of OSCC, suggesting that A2bR promotes cell proliferation in OSCC, while A3R may be involved in OSCC progression by regulating tumor cell apoptosis and immune microenvironment.