Occurrence Of Oral Squamous Cell Carcinoma Research Articles

PLCE1 as a diagnostic and prognostic biomarker by promoting the growth and progression of oral squamous cell carcinoma.

This study aimed to explore the role of phospholipase C epsilon1 (PLCE1) in the growth and progression of oral squamous cell carcinoma (OSCC) and determine its potential as a biomarker with respect to diagnosis, prognosis and treatment of OSCC. The expression level of PLCE1 in tissue specimens was detected by immunohistochemistry (182 OSCC cases and 76 controls) and its relationship to clinicopathological parameters was analyzed. Then, the diagnostic value of PLCE1 in OSCC was verified by constructing the receiver operating characteristic (ROC) curve. Kaplan-Meier and Cox analysis were performed to investigate the role of PLCE1 in predicting the prognosis of OSCC patients. Furthermore, the effects of PLCE1 on the occurrence and development of OSCC were revealed by knocking down the level of PLCE1. PLCE1 was mainly located in the cytoplasm of OSCC cells, and its level in OSCC tissues was obviously higher than in adjacent normal tissues. While the expression of PLCE1 did not correlate with clinicopathological parameters of OSCC. The area under the ROC curve (AUC) of PLCE1 was 0.865 with a sensitivity of 75.8% and a specificity of 78.8%. Besides, high expression of PLCE1 suggested a worse prognosis in OSCC patients than those with low expression. The knockdown of PLCE1 obviously inhibited proliferation, migration, and invasion of OSCC cells, and induce G0 cell cycle phase arrest and apoptosis, thus preventing the progression of OSCC. PLCE1 may cause carcinogenesis and development of OSCC, which provide a novel possibility in diagnosis, prognosis and treatment of OSCC.

FANCONI ANEMIA - ORAL REPERCUSSIONS AND DENTAL MANAGEMENT

<h3>Objectives</h3> Fanconi anemia (FA) is a rare genetic disease characterized by bone marrow failure and increased predisposition for cancer development, mainly oral squamous cell carcinoma (OSCC). The aim of this study was to discuss oral repercussions and dental management in patients with FA, focusing on the relevance of the dental surgeon (DS) in the OSCC prevention. <h3>Study Design</h3> A literature research was conducted in the PubMed, Scielo, and Google Scholar databases using the descriptors: Fanconi anemia, squamous cell carcinoma, oral manifestations, dental management, and dentistry. <h3>Results</h3> Besides the high risk of cancer development, patients with FA could also present aplastic anemia, pancytopenia, short stature, and kidney and heart defects. The only effective treatment to the bone marrow failure is allogeneic hematopoietic stem cell transplantation; however, this does not prevent OSCC occurrence. Therefore, the DS is important to prevent potential infections and to diagnose OSCC in its early stages, allowing to these patients a better opportunity for cure. <h3>Conclusions</h3> Dental follow-up of patients with FA should be mandatory because DS plays an essential role not only in the management of oral manifestations but also in the early detection of the OSCC that sometimes could be presented as the first FA symptom.

Potentially -malignant disorders

It is estimated that more than one million new oral cancer cases are being detected annually in the Indian subcontinent, of which 90% are oral squamous cell carcinoma (OSCC). Oral potentially malignant disorder (OPMD) are associated with increased rate of occurrence of OSCC of lips or oral cavity. Transformation of oral cancer from OPMD is common, especially in South Asian countries like India, where tobacco and arecanut consumption is prevalent. Early diagnosis and timely treatment of PMD’s may help to prevent its malignant transformation into oral cancer. The aim of the article is to highlight the risk factors, etiology, clinical presentation of PMD, thus helps in early detection and treatment, thereby reducing incidence of oral cancer.

Metabolomic Analysis Reveals that SPHK1 Promotes Oral Squamous Cell Carcinoma Progression through NF-κB Activation.

Metabolic disorders are significant in the occurrence and development of malignant tumors. Changes of specific metabolites and metabolic pathways are molecular therapeutic targets. This study aims to determine the metabolic differences between oral squamous cell carcinoma (OSCC) tissues and paired adjacent noncancerous tissues (ANT) through liquid chromatography-mass spectrometry (LC-MS). SPHK1 is a key enzyme in sphingolipid metabolism. This study also investigates the potential role of SPHK1 in OSCC. This study used LC-MS to analyze metabolic differences between OSCC tissues and paired ANT. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were applied to explain the significance of phospholipid metabolism pathways in the occurrence and development of OSCC. Through further experiments, we confirmed the oncogenic phenotypes of SPHK1 in vitro and in vivo, including proliferation, migration, and invasion. The sphingolipid metabolic pathway was significantly activated in OSCC, and the key enzyme SPHK1 was significantly upregulated in oral cancer tissues, predicting poor OSCC prognosis. In this study, SPHK1 overexpression was associated with high-grade malignancy and poor OSCC prognosis. SPHK1 targeted NF-κB by facilitating p65 expression to regulate OSCC tumor progression and promote metastasis. This study identified metabolic differences between OSCC and paired ANT, explored the carcinogenic role of overexpressed SPHK1, and revealed the association of SPHK1 with poor OSCC prognosis. SPHK1 targets NF-κB signaling by facilitating p65 expression to regulate tumor progression and promote tumor metastasis, providing potential therapeutic targets for diagnosing and treating oral tumors.

Clinicopathological Significance of AKT1 and PLK1 Expression in Oral Squamous Cell Carcinoma.

Purpose Oral squamous cell carcinoma (OSCC) is the sixth leading cause of cancer-related death worldwide and is characterized by metastasis and recurrence. We aimed to evaluate the expression of AKT1 and PLK1 in OSCC and identify their correlation with the clinical and histological features and prognosis of patients with OSCC. Methods Tissue samples were collected from 70 patients with OSCC and 50 patients with normal oral mucosa. The expression levels of AKT1 and PLK1 in OSCC tissues and normal oral mucosa were detected by immunohistochemistry. The chi-square test was used to identify correlations between the expression levels of AKT1 and PLK1 with patients' clinicopathologic characteristics. Survival analysis was assessed by the Kaplan–Meier method. Spearman's rank correlation test was used to determine the relationships between AKT1 and PLK1 expressions. The bioinformatics database GEPIA was used to verify the experimental results. Results The chi-square test and Fisher's exact test showed that the positive expression rate of AKT1 and PLK1 in OSCC tissue was significantly higher than that in the normal oral mucosa (P < 0.05). PLK1 expression levels were significantly correlated with tumor stage and size (P < 0.05). Kaplan–Meier analysis showed that the survival time of AKT1 and PLK1 with high expression was significantly shorter than that of patients with low expression (P < 0.05). Spearman's rank correlation test showed a strong correlation between AKT1 and PLK1 expression in OSCC tissue (R = 0.53; P < 0.05). GEPIA bioinformatics database analysis results show that the expression and overall survival of AKT1 and PLK1 analysis and the correlation analysis of AKT1 and PLK1 were consistent with experimental results. Conclusion AKT1 and PLK1 expressions are associated with the occurrence and progression of OSCC and may be used as diagnostic and prognostic indicators of OSCC. There may be a correlation between AKT1 and PLK1 in OSCC tissue.

Co-Culture of MSCs with miR-496 Prompts Epithelial-Mesenchymal Transformation of Oral Squamous Cell Carcinoma (OSCC)

This study discusses the molecular mechanism of co-culture of MSCs with miR-496 in the EMT of OSCC. miR-496 expression in OSCC tissues and cells was detected by qRT-PCR. The MSCs+si-NC, MSCs+pc-DNA-NC, MSCs+si-miR-496, MSCs+pc-DNA-miR-496 was transfected into SCC-PKUs to analyze cell apoptosis, proliferation and clone formation as well as the expression of proteins related with EMT. miR-496 in OSCC tissues was elevated and positively related with the clinical stage of OSCC patients. The cell activity and invasive ability of SCC-PKU was increased after co-culture of MSCs and pc-DNA-miR-496 along with increased expression of EMT-related proteins. However, all above changes were reversed after treatment with MSCs and si-miR-496. In conclusion, co-culture of MSCs and miR-495 prompts the occurrence and development of OSCC through regulating EMT processes, indicating that they might be novel targets for the treatment of OSCC.

Clinical and Histological Prognostic Factors of Recurrence and Malignant Transformation in a Large Series of Oral Potentially Malignant Disorders

BackgroundOral potentially malignant disorders (OPMDs) represent a heterogeneous set of different histological lesions, characterized by the capacity to transform in oral squamous cell carcinoma (OSCC). Despite optimal surgical treatment, approximately 20%–30% of OPMDs may evolve into OSCC. No clear clinical/histological factors are able to identify OPMDs at higher risk of malignant transformation.Materials and MethodsWe considered surgically treated patients with a diagnosis of OPMDs, enrolled from 1996 to 2019 at ASST Spedali Civili of Brescia without a diagnosis of OSCC within the previous 2 years. Clinical and histological characteristics were recorded. Outcomes of interest were recurrence-free survival (RFS), defined as the time from surgery for primary OPMD to any relapse of OPMD or malignant transformation, whichever occurred first, and carcinoma-free survival (CFS), defined as the time from surgery for OPMD to malignant transformation.ResultsWe retrospectively reviewed 106 OPMDs cases. Median age at first diagnosis was 64 years old (IQR = 18.75); female patients comprise 51.9% of the cases. During a median follow-up of 30.5 months (IQR = 44), in 23.5% of patients, malignant transformation occurred. RFS at 1, 5, and 10 years was 92.4%, 60.9%, and 43.2%, respectively. Female sex and history of previous OSCC were independent risk factors for RFS. CFS at 1, 5, and 10 years of follow-up was 97.1%, 75.9%, and 64.4%, respectively. Previous OSCC was an independent risk factor for CFS.ConclusionsIn this large series of OPMDs, only previous diagnosis of OSCC was a prognostic factor for further OSCC occurrence. Given the lack of additional clinical/pathological prognostic factors, we advocate further studies into molecular characterization of OPMDs to better stratify the risk of malignant transformation.

ORAL SQUAMOUS CELL CARCINOMA IN PATIENTS UNDER THE AGE OF 30, A LARGE CASE SERIES

<h3>Introduction</h3> Oral squamous cell carcinoma (OSCC) is typically associated with older adults often with established relationship to tobacco and/or alcohol abuse. OSCC is rare in children and young adults without traditional risk factors. This case series encompasses an archival review of OSCC affecting patients under 30 years of age with analyses of demographics, clinical presentation, and histologic findings. Materials and Methods: An IRB approved study queried the archives of the UF Oral Pathology Biopsy Service from 19942019. All cases of OSCC affecting patients under 30 years were identified. Age, gender, location, clinical presentation, diagnosis, and grading were recorded, and slides were reviewed for diagnostic consensus. <h3>Results</h3> During this span only 30 cases (0.76%) were identified in patients under 30 years of age out of a total of 3971 OSCC cases. Males (53.33%) were affected more commonly. An age range of 8 to 30 years with a mean of 24 years was noted. Only 3 were known smokers. In descending order, the lateral tongue, ventral tongue, and maxillary gingiva were most frequently involved. A wide spectrum of clinical diagnoses were obtained most consisting of reactive lesions. A few clinicians considered dysplasia and OSCC. Symptoms including pain, burning, swelling or dysphagia were present in 65.6% of cases. The histologic grade ranged from well to poorly differentiated. Perineural invasion was noted in 28.13%. Three out of 4 cases with P16 immunostaining at the time of sign out were positive. <h3>Conclusion</h3> This study underscores the rare occurrence of OSCC in children and young adults. This may potentially lead to low clinical suspicion, misdiagnosis, and failure of prompt treatment. Further longitudinal multicenter studies with detailed medical history, treatment, and prognostic data may cast light on better understanding of the etiology of OSCC in young patients, aid prevention, and improve outcomes.

Prevalence and Characteristics of Oral Squamous Cell Carcinoma in Fiji: A Retrospective Study

BACKGROUND: Oral squamous cell carcinoma (OSCC) is malignant epithelial neoplasm that affects the oral cavity. Despite the large number of studies on OSCC in the literature, details on the demographic profile of these lesions in different populations are limited, especially amongst the Fijian population, thus this study aimed to determine the prevalence and characteristics of OSCC cases diagnosed from 2011 to 2015 at the Colonial War Memorial Hospital (CWMH), Suva, Fiji Islands. &#x0D; &#x0D; MATERIALS &amp;amp; METHODS: A retrospective quantitative study was carried out at the CWMH Histology department looking at OSCC cases diagnosed from 2011&amp;ndash;2015. All confirmed cases were included in the study and excluded cases were suspected cases that were pending diagnosis and children. An extraction sheet was used for data collection which was designed to meet the requirements of study finding. This data was entered in SPSS software and then analyzed using the simple analytical tool as bar graphs and tables.&amp;nbsp; &#x0D; &#x0D; RESULTS: There were 74 OSCC cases diagnosed in the study period. The occurrence of OSCC cases over the 5-year period was fluctuant with the year 2013 recording the highest number of cases (24 cases, 32%). During the reported period, more men suffered (53 cases, 72%) from this condition with the tongue (40%) being the commonest oral cancer site followed by the lip and vermillion border (28%). Individuals in the 40 to 60 years&amp;rsquo; age group (35 cases, 47.3%) were mostly affected with the I-taukei population (38 cases, 51.4%) recording the highest occurrence of OSCC. The results show that, the common occurrence is the tongue (40.5%) while the least presentation sight is Buccal mucosa/buccal sulcus area (8.1%). &#x0D; &#x0D; CONCLUSION: The study concluded that more men suffer from oral squamous cell carcinoma compared to woman and the ethnicity that was most affected was I-taukei population. More detailed record keeping and reporting of oral cancer is needed to help evaluate progress in controlling oral cancer in the Fiji Islands. This availability of geographic data would further assist the Ministry of Health of Fiji in data collection and planning of preventative activities

Is oral lichen planus a potential malignant disorder?: A critical appraisal.

Dear Editor, “The difficulty lies not in new ideas, but in escaping old ones” - John Keynes Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease of unknown etiology.[1] One of the most controversial aspects of OLP is its potentially malignant nature.[2] Numerous studies on OLP have reported varying malignant transformation rates of OLP from very high to almost negligible giving rise to conflicting findings.[23] Recent studies have reported malignant transformation of OLP ranging between 0.44 and 2.28%.[456] In this letter, we would like to put forth our views regarding the malignant transformation of OLP and its inclusion in oral potential malignant disorders (OPMDs). GLOBOCAN in 2018 reported the estimated average age-standardized rate of oral cancers worldwide as 4 per 100 000 (range between 0.4 and 20.4 per 100 000). So, based on the estimated worldwide prevalence of OLP, 5–20 OLP patients per 100 000 of the general population will develop oral cancer within 5 years. On comparing the global cancer prevalence rate with OLP, it shows that most oral squamous cell carcinoma (OSCC) cases have apparently developed from OLP, which seems questionable.[7] In most of the systematic reviews and meta-analyses, after application of strict criteria to the clinical appearance of the affected site and transformed location, histopathological presentation, habits, comorbid conditions, age, and gender, it is evidenced that the malignant transformation rate of OLP is exaggerated due to insufficient diagnostic criteria, inaccurate follow-up and/or average quality of investigation.[8] The diagnosis of OLP requires the presence of both clinical and histopathological features.[9] Unfortunately, many times diagnosis is solely based on clinical judgement without biopsy. It is quite possible that OSCC may clinically present as OLP and the clinician may institute topical/systemic steroid therapy without histopathological examination. Subsequent biopsy of those unresponsive lesions turns out to be OSCC, resulting in an inadvertent increase in the malignant transformation rate of OLP in studies. Topical/systemic steroid treatment results in decreased local immunity, providing a potential cause for conversion to cancer that cannot be ignored.[31011] Systemic condition like diabetes causes disturbances in cellular and humoral immune functions, reducing the immunity in OLP-affected patient which may lead to malignant transformation.[12] Association of tobacco and/or alcohol may also play a role in mucosal alteration at the microscopic level, increasing the likelihood of malignant transformation.[3] Though the investigators have supported the potentially malignant nature of OLP, a small but significant number of OSCC occur in non-smokers and non-drinkers with a range of 3–24%. Even with this finding the overall malignant transformation rate of OLP remains lower compared to the occurrence of OSCC in non-smokers and non-drinkers (OLP—2.28% vs OSCC in non-smokers and non-drinkers 3–24%).[6131415] Based on the above observations, it is high time for us to rethink whether OLP should still be considered as an OPMD? Once diagnosed with OLP, informing the patient about possible malignant transformation induces cancerophobia, causing stress and disturbing their emotional status further aggravating the signs and symptoms of OLP.[16] Until then, based on the literature reporting the potentially malignant nature of OLP, we suggest the need for psychological counseling for all OLP patients. This will definitely serve to alleviate their anxiety, thus making them more receptive to treatment. We hope our letter will generate a healthy discussion among the readers to arrive at a common consensus by putting forth their views on this topic. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Role of hyaluronan mediated motility receptor gene in oral squamous cell carcinoma and clinical prognosis.

To screen genes related to the prognosis of oral squamous cell carcinoma (OSCC), and to explore its role and mechanism in the occurrence and development of OSCC. The data and the biological information in 330 OSCC tumor samples with head and neck squamous cell carcinoma (HNSCC) (OSCC group) and 37 normal samples (normal sample group) were screened and included, which came from the cancer genome atlas (TCGA) database. The differentially expressed genes were screened out by biological information analysis between the 2 groups. Furthermore, according to the tumor T grade (T1+T2 group: 114 cases, T3+T4 group: 216 cases), metastasis (positive group: 163 cases, negative group: 167 cases) and pathological grade (G1+G2 group: 244 cases, G3 +G4 group: 86 cases), the samples were divided into different groups respectively, and the differential genes were obtained separately, then the intersections of the differential expressed genes related to the prognosis of OSCC were screened. The different gene with the largest different multiples [hyaluronan mediated motility receptor (HMMR)] was selected for the next step in order to explore the relationship between HMMR and clinical grading (Stage I+II group: 69 cases, Stage III +IV group: 261 cases), as well as the relationship between T grade, metastasis and pathological grade. According to the median value of HMMR expression, the samples were divided into a high expression group and a low expression group (high expression group: 165 cases, low expression group: 165 cases); Kaplan-Meier survival analysis was used to explore the relationship between HMMR expression and prognosis. Tumor tissue specimens and corresponding normal oral mucosal tissue specimens in 50 OSCC patients, who underwent surgery in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from January 2014 to January 2016, were collected. Real-time RT-PCR and Western blotting and immunohistochemistry were used to verify the bioinformatics analysis results. Kaplan-Meier survival analysis was used to examine the relationship between the positive and negative expression of HMMR immunohistochemical staining (positive group: 32 cases, negative group: 18 cases) and prognostic related factors, and Cox regression analysis model was used to explore the prognostic risk factors of OSCC. The cell proliferation experiment and the cell scratch experiment were used to evaluate the effect of down-regulation of HMMR on the proliferation and migration of OSCC cells. HMMR was highly expressed in OSCC tissues. Compared with the low HMMR expression group, the prognostic related factors in the HMMR high expression group was significantly lower, with significant difference (all P<0.05); the high expression of HMMR was significantly related with the T grade (RR=1.33, P<0.05), lymphonodus metastasis (RR=1.74, P<0.05), the clinical stage (RR=1.49, P<0.05), and it was an independent prognostic risk factor for OSCC (RR=1.45, P<0.05). Down-regulation of HMMR can inhibit the proliferation and migration of OSCC cells, with significant difference (P<0.05 or P<0.01). HMMR, as a proto-oncogene of OSCC, can promote the occurrence and development of OSCC, and it may be used as a potential early diagnostic marker and a new target for therapy.

Matrisome provides a supportive microenvironment for oral squamous cell carcinoma progression

Oral squamous cell carcinoma (OSCC) is a common pernicious tumor in the head and neck regions. However, the function of tumor extracellular matrix (ECM) has not been elucidated. A tissue engineering method was applied for remodeling ECM through decellularization. The cellular components were removed, and the biological composition was mostly preserved. Proteomics was performed to analyze the characterization between normal and tumor ECM. According to LC-MS/MS results, 26 proteins just showed in tumor ECM, and 14 proteins only showed in late-stage tumor ECM. KEGG pathway analysis showed that most variant proteins were linked to metabolic regulation and tumor immunity (such as SCC-Ag1, LOX). To affirm the influence of tumor ECM on the progression of OSCC, tumor cells and macrophages were co-cultured with ECM scaffold. Marked differences in proliferation, apoptosis, and migration of OSCC cells were observed between tumor and normal ECM. Tumor ECM polarized macrophages towards an anti-inflammatory phenotype (higher IL-10 and CD68, and relatively lower CD86 and IL1-β). Collectively, these findings suggest that tumor ECM served as a permissive role in OSCC progression. SignificanceThe variation between OSCC ECM and normal ECM confirm tumor ECM plays a significant role in OSCC deterioration, which is conducive to exploring the occurrence and progression mechanisms of OSCC, and further improving the curative effect of this disease.

Hepatocyte Growth Factor Overexpression Slows the Progression of 4NQO-Induced Oral Tumorigenesis.

ObjectivesTo investigate the role of hepatocyte growth factor (HGF)/c-Met signaling in oral malignant transformation.MethodsWe used immunohistochemistry to investigate HGF and c-Met expression in 53 oral squamous cell carcinoma (OSCC) specimens and 21 adjacent nontumor specimens and evaluated the associations between HGF and c-Met expression and clinicopathological parameters. Additionally, HGF-overexpression transgenic (HGF-Tg) and wild-type (Wt) mice were treated with 4-nitroquinoline-1-oxide (4NQO) to induce oral carcinogenesis for 16 weeks. At 16, 20, and 24 weeks, tongue lesions were collected for clinical observation; estimation of HGF, c-Met, and PCNA expression; apoptosis (TUNEL) assays; and RNA sequencing (RNA-seq).ResultsHGF and c-Met were positively expressed in 92.5% and 64% of OSCC samples, respectively. High HGF expression was significantly associated with smaller tumor size (p = 0.006) and inferior TNM stage (p = 0.032). No correlation between HGF and c-Met levels and other clinical parameters or prognosis was noted. In addition, HGF and c-Met expression was elevated in 4NQO-induced lesions of Wt mice. Compared with Wt mice, HGF-Tg mice have lower tumor incidence, number, volume, and lesion grade. In addition, the percentage of PCNA-positive cells in Wt mice was significantly higher than that in HGF-Tg mice at different time points. At 16 weeks, HGF-Tg mice exhibited less apoptotic cells compared with Wt mice (p < 0.000), and these levels gradually increased until the levels were greater than that of Wt mice at 24 weeks (p < 0.000). RNA-seq data revealed that 140 genes were upregulated and 137 genes were downregulated in HGF-Tg mice. KEGG enrichment analysis showed that upregulated differentially expressed genes (DEGs) are highly correlated with oxidative and metabolic signaling and that downregulated DEGs are related to MAPK and PI3K-AKT signaling.ConclusionsHGF and c-Met expression is upregulated in OSCC tissues and is associated with the occurrence and development of OSCC. HGF overexpression in normal oral epithelial tissue can inhibit 4NQO-induced tumorigenesis potentially through inhibiting proliferation and accelerating apoptosis via MAPK and PI3K-AKT signaling.

Identification of biomarkers related to glycolysis with weighted gene co-expression network analysis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common tumor in the oral cavity and maxillofacial region. Increasing evidence suggests that aerobic glycolysis plays an important role in the occurrence, development, and prognosis of OSCC. Therefore, the identification of biomarkers related to glycolysis in OSCC represents considerable potential for improving its treatment. In the present study, a single-sample gene-set enrichment analysis (ssGSEA) algorithm with weighted gene co-expression network analysis (WGCNA) were used to quantify the degree of glycolysis and identify key modules with the greatest correlation with glycolysis. Glycolytic scores significantly correlated with prognosis. In the key module 5 HUB genes were finally selected, which displayed a robust predictive effect. The expressions of key genes were associated with glycolysis. The research comprehensively analyzed the glycolysis of OSCC and identified several biomarkers related to glycolysis. These biomarkers may represent potential therapeutic targets for future OSCC therapy.

CXCL3 overexpression affects the malignant behavior of oral squamous cell carcinoma cells via the MAPK signaling pathway.

CXCL3, a member of the chemokine family, plays a key role in angiogenesis, tumorigenesis, and cell invasion and migration. However, the role of CXCL3 in oral squamous cell carcinoma (OSCC) remains unclear. The purpose of this study is to explore the expression of CXCL3 in OSCC and to explore the role of CXCL3 in human OSCC HSC-4 cells and its molecular mechanism. The expression of CXCL3 in human OSCC tissues was assessed using immunohistochemistry and The Cancer Genome Atlas (TCGA) database. In vivo and in vitro experiments investigated the effects of CXCL3 on the proliferation, migration, and invasion of OSCC cells. The expression of CXCL3 in tumors is higher than that in normal tissues and is closely related to stage and lymph node metastasis. In vitro experiments showed that the proliferation and migration ability of HSC-4 cells treated with exogenous recombinant human CXCL3 and HSC-4 cells overexpressing CXCL3 were enhanced. Experiments on xenografts in nude mice showed that overexpression of CXCL3 promotes tumor growth in vivo. GSEA showed that patients with high expression of CXCL3have varying degrees of enrichment in cytokine-cytokine receptor interaction, apoptosis, Jak-STAT signaling pathway, and MAPK signaling pathway. Subsequent mechanism studies showed that the use of ERK1/2 blocker PD98059 can attenuate the proliferation and migration effects induced by CXCL3. CXCL3 is involved in the occurrence of OSCC and may become a potential therapeutic target.

Intratumoural heterogeneity and clone evolution of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral malignancy. Our study uses multipoint materials to explore the heterogeneity and metastasis mechanism of OSCC to find more accurate molecular markers and new therapeutic targets.By using whole-exome capture and sequencing and tumor evolution analysis, we found that most clone-driven mutations were located in the branches of tumor phylogenetic tree, such as COTL1, CASP8, and PROCR. Most clone-driven OSCC mutations occur mainly in tumor suppressor genes, including TP53, SFRP4, and NOTCH1.Our study on intratumor heterogeneity (ITH) and clonal evolution provides an important molecular basis for further understanding of OSCC occurrence and development and metastasis and provides potential targets for the treatment of this disease.

Assessment of Potential Prognostic Value of Peroxiredoxin 1 in Oral Squamous Cell Carcinoma.

PurposeThe role of the peroxiredoxin (PRDX) family in oral squamous cell carcinoma (OSCC) remains unclear. This study aimed to investigate the expression of PRDXs and their effects on the prognosis in OSCC.MethodsThe expression of PRDXs and their effects on prognosis were analysed in 216 OSCC samples from The Cancer Genome Atlas (TCGA) database. OSCC tissues and adjacent noncancerous tissues (ANTs) were obtained from 68 clinical patients. Quantitative real-time (qRT)-PCR, Western blot, and immunohistochemical (IHC) staining were used to verify the relationship between the expression level of PRDX1 and different clinical features. Gene set enrichment analysis (GSEA) was used to examine the molecular mechanism of PRDX1 in OSCC.ResultsPRDX1 was found to be the only gene in PRDX family that highly expressed in OSCC samples and affected the prognosis of patients with OSCC. PRDX1 expression was significantly related to tumor stage, lymphatic metastasis, and pathological grade. A nomogram consisting of tumor stage, N stage, and PRDX1 level was constructed. GSEA showed that high expression of PRDX1 involved many cancer-related molecular functions and signaling pathways.ConclusionPRDX1 may play an important role in the occurrence and development of OSCC, and may be a potential new target for OSCC treatment.

Arecoline induces epithelial-mesenchymal transformation and promotes metastasis of oral cancer by SAA1 expression.

Arecoline, the main alkaloid of areca nut, is well known for its role in inducing submucosal fibrosis and oral squamous cell carcinoma (OSCC), however the mechanism remains unclear. The aim of this study was to establish an arecoline‐induced epithelial‐mesenchymal transformation (EMT) model of OSCC cells and to investigate the underlying mechanisms. CAL33 and UM2 cells were induced with arecoline to establish an EMT cell model and perform RNA‐sequence screening. Luminex multiplex cytokine assays, western blot, and RT‐qPCR were used to investigate the EMT mechanism. Arecoline at a concentration of 160 μg/ml was used to induce EMT in OSCC cells, which was confirmed using morphological analysis, transwell assays, and EMT marker detection. RNA‐sequence screening and Luminex multiplex cytokine assays showed that many inflammatory cytokines (such as serum amyloid A1 [SAA1], interleukin [IL]‐6, IL‐36G, chemokine [CCL]2, and CCL20) were significantly altered during arecoline‐induced EMT. Of these cytokines, SAA1 was the most highly upregulated. SAA1 overexpression induced EMT and promoted the migration and invasion of CAL33 cells, while SAA1 knockdown attenuated arecoline‐induced EMT. Moreover, arecoline enhanced cervical lymph node metastasis in an orthotopic xenograft model of the tongue established using BALB/c nude mice. Our findings revealed that arecoline induced EMT and enhanced the metastatic capability of OSCC by the regulation of inflammatory cytokine secretion, especially that of SAA1. Our study provides a basis for understanding the mechanism of OSCC metastasis and suggests possible therapeutic targets to prevent the occurrence and development of OSCC associated with areca nut chewing.

Social isolation stress facilitates chemically induced oral carcinogenesis.

Social isolation has affected a large number of people and may lead to impairment of physical and mental health. Although stress resulting from social isolation may increase cancer progression, its interference on tumorigenesis is poorly known. In this study, we used a preclinical model to evaluate the effects of social isolation stress on chemically induced oral carcinogenesis. Sixty-two 21-day-old male Wistar rats were divided into isolated and grouped groups. After 90 days of age, the rats from both groups underwent oral carcinogenesis with 4-nitroquinoline 1-oxide (4NQO) for 20 weeks. All rats were assessed for depressive-like behavior and euthanized for oral squamous cell carcinoma (OSCC) diagnosis and measurement of inflammatory mediators in the tumor microenvironment. Social isolation stress increased the OSCC occurrence by 20.4% when compared to control. Isolated rats also showed higher tumor volume and cachexia than the grouped rats. Social isolation did not induce changes in the depressive-like behavior after carcinogenic induction. Tumors from stressed rats had increased levels of the inflammatory mediators, TNF-alpha, IL1-beta and MCP-1. The concentrations of TNF-alpha and MCP-1 were significantly increased in the large tumors from isolated animals. Higher tumor levels of TNF-alpha, IL-6, IL1-beta and MCP-1 were positively correlated with OSCC growth. This study provides the first evidence that social isolation stress may facilitate OSCC occurrence and tumor progression, an event accompanied by increased local levels of inflammatory mediators.

Long Noncoding RNA ZFAS1 Promotes Progression of Oral Squamous Cell Carcinoma Through Targeting miR-6499-3p/CCL5 Axis.

Oral squamous cell carcinoma (OSCC) ranks sixth among malignancies in the world, and there are 200,000 new cases annually, rendering OSCC a significant global public health issue that has caused great burdens on patients, society, and the economy. Despite great progress in diagnosis and treatment methods, patient survival has not been greatly enhanced. Hence, there is an urgent need to identify novel targets that can serve as early diagnostic and therapeutic biomarkers for OSCC. Long non-coding RNAs (lncRNAs) participate in several cancer types, including OSCC. This work identified the competing endogenous RNA network related to lncRNA zinc finger nuclear transcription factor, X-box binding 1-type containing 1 antisense RNA 1 (ZFAS1) in OSCC, as well as the corresponding downstream targets. Firstly, we identified the lncRNA ZFAS1 levels in OSCC cells and tissues and confirmed its relationship to tumor progression. Secondly, we identified a lncRNA-miRNA-mRNA network, which was closely associated with OSCC development using bioinformatics methods. Next, our hypothesis that lncRNA ZFAS1 modulates OSCC progression was verified with in vitro and in vivo experiments. Firstly, we found lncRNA ZFAS1 expression increased within OSCC cells and tissues and was positively associated with tumor progression. Secondly, its lncRNA-miRNA-mRNA network was determined, and the target of ZFAS1 was identified as miR-6499-3p/C-C motif chemokine ligand 5 (CCL5). Mechanistically, we found that ZFAS1 up-regulated CCL5 by competitively sponging miR-6499-3p. Further studies demonstrated that ZFAS1 promoted tumor progression in vivo and in vitro. Our results indicate that ZFAS1 serves as a crucial oncogenic factor in OSCC occurrence and development and may therefore serve as a possible therapeutic target for OSCC.