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1.
Background:This study aimed to evaluate LAMP3 (CD208) gene expression in oral squamous cell carcinoma (OSCC) and dysplastic oral epithelium by quantitative real-time polymerase chain reaction (qPCR) and compare LAMP3 expression in different disease grades and stages.Methods:In this study, 60 OSCC and dysplastic oral epithelium samples were obtained from the Mashhad University of Medical Sciences together with their demographic and clinicopathological documents. LAMP3 expression was measured by qPCR.Results:LAMP3 expression was significantly greater in OSCC than in dysplasia samples (P=0.001), in grade III OSCC than in grades I and II, and also greater in advanced than in early OSCC disease stage (P=0.001).Conclusion:The significantly greater LAMP3 expression in OSCC than in dysplastic epithelium indicates a role for LAMP3 in carcinogenesis in oral mucosa. Our results suggest LAMP3 may be useful as an anticancer target and/or to predict disease pathogenesis in OSCC patient’s cells.Key Words: Clinicopathological, Grade, Epithelial dysplasia, LAMP3, Stage, Squamous cell carcinoma.  相似文献   

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目的:探讨口腔鳞状细胞癌(Oral Squamous Cell Carcinoma,OSCC)中B7-H1和B7-H4的表达及其临床意义,并为OSCC的临床诊断、治疗、判断预后及预防等提供依据。方法:采用免疫组织化学S-P法检测B7-H1及B7-H4在60例OSCC及20例非肿瘤患者正常口腔黏膜组织(NOM)中的表达情况,分析两者与OSCC临床病理特征的相关性。结果:B7-H1在OSCC组织中表达显著高于在NOM组织中表达(29例,48.3%v4例,20%,x~2=4.969,P0.05);B7-H4在OSCC组织中表达亦显著高于在NOM组织中表达(31例,51.7%v5例,25%,x~2=4.310,P0.05)。B7-H1与B7-H4在OSCC组织的表达都与TNM分期、淋巴结转移和肿瘤分化程度显著相关(P0.05),而与年龄、性别及肿瘤直径大小等无关。OSCC组织中B7-H1和B7-H4的高表达呈显著性正相关性(x~2=5.613 P0.05),60例组织中B7-H1和B7-H4共表达现象有11例(18.3%),NOM中未发现两者共表达现象。结论:B7-H1和B7-H4过表达与OSCC发生、发展及预后有关,可以作为预后指标。  相似文献   

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目的:研究人丝氨酸/精氨酸富有剪接因子1(SRSF1)和凋亡抑制因子(Survivin)在口腔鳞状细胞癌(OSCC)组织和正常口腔黏膜(NOM)中的表达,探究两因子在OSCC中的相关性及其临床意义。方法:采用免疫组织化学SP法,检测两因子在60例OSCC组织、20例NOM组织中的表达,并结合组织学分级、淋巴结转移及临床分期等相关的信息进行相关性分析。结果:在NOM中SRSF1和Survivin低表达,在OSCC组织中均高表达,比例分别为68.3%和60%。SRSF1和Survivin与淋巴结转移、组织学分级以及临床分期之间存在统计学差异(P0.05);并且在OSCC组织中二者之间表达存在着显著正相关性,(r=0.541,P0.05)。结论:SRSF1和Survivin在OSCC中均高表达,与口腔鳞癌的发生、发展密切相关并具有协同作用。  相似文献   

5.
Oral squamous cell carcinoma (OSCC) constitutes >90% of oral cancers and is the sixth most common malignancy among males worldwide and the fourth leading cause of death due to cancer among males in Taiwan. However, most patients do not receive a diagnosis of OSCC until the late stages, which have a lower survival rate. The use of molecular marker analysis to identify early-stage OSCC would permit optimal timing for treatments and consequently prolong survival. The aim of this study was to identify biomarkers of OSCC using the Illumina GoldenGate Methylation Cancer Panel, which comprised a total of 1,505 CpG sites covering 807 genes. Samples of buccal mucosa resected from 40 OSCC patients and normal tissue samples obtained from 15 patients (normal mucosa from OSCC patients or from patients undergoing surgery unrelated to OSCC) were analyzed. Fms-related tyrosine kinase 4 (FLT4) methylation exhibited a perfect specificity for detecting OSCC, with an area under the receiver operating characteristic curve of 0.91 for both all-stage and early-stage OSCC. Methylation of 7 genes (ASCL1, FGF3, FLT4, GAS7, KDR, TERT, and TFPI2) constitutes the top-20 panels for detecting OSCC. The top-20 panels for detecting early-stage OSCC contain 8 genes: ADCYAP1, EPHA7, FLT4, GSTM2, KDR, MT1A, NPY, and TFPI2. FLT4 RNA expression and methylation level were validated using RT-PCR and a pyrosequencing methylation assay. The median level of FLT4 expression was 2.14-fold for normal relative to OSCC tissue samples (P < 0.0001). Among the 8 pyrosequenced FLT4 CpG sites, methylation level was much higher in the OSCC samples. In conclusion, methylation statuses of selected genes, and especially FLT4, KDR, and TFPI2, might be of great potential as biomarkers for early detection of buccal OSCC.  相似文献   

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Oral leukoplakia (OL) is the most common premalignancy in the oral cavity and can progress to oral squamous cell carcinoma (OSCC). SMAD4 is a tumor suppressor implicated in multiple cancer types including OSCC. To assess the role of SMAD4 in oral leukoplakia malignant transformation, the authors investigated SMAD4 expression patterns in OL and OSCC using a highly specific antibody and correlated the patterns with the risk of malignant transformation oral leukoplakia. Immunohistochemistry and a quantitative imaging system were used to measure SMAD4 expression in OL from 88 OL patients, including 22 who later went through malignant transformation, and their OSCC counterpart. Forty-three (48.9%) of the 88 OL patients had strong SMAD4 expression. SMAD4 expression had no significant correlation with patients'' clinicopathological parameters. Interestingly, 17 (39.5%) of the 43 OL lesions with strong SMAD4 expression went through malignant transformation whereas only 5 (11.1%) of the 45 OL lesions with weak SMAD4 expression did so (p = 0.002). The SMAD4 expression in OL was much higher than that in their OSCC counterpart. Kaplan-Meier analysis revealed that the combination of SMAD4 expression and histological grade of dysplasia (p = 0.007) is a better predictor for the malignant transformation of oral leukoplakia. In the multivariate analysis, both SMAD4 expression and grade of dysplasia were identified as independent factors for OL malignant transformation risk (p = 0.013 and 0.021, respectively). It was concluded that high SMAD4 expression may be indicative of an early carcinogenic process in OL and serve as an independent biomarker in assessing malignant transformation risk in patients with OL, and the combination of SMAD4 expression and histological grade of dysplasia is a better predictor for the malignant transformation of oral leukoplakia.  相似文献   

8.
Oral and oropharyngeal squamous cell carcinomas (OSCC) are among the most common cancers worldwide, with approximately 60% 5-yr survival rate. To identify potential markers for disease progression, we used Affymetrix U133 plus 2.0 arrays to examine the gene expression profiles of 167 primary tumor samples from OSCC patients, 58 uninvolved oral mucosae from OSCC patients and 45 normal oral mucosae from patients without oral cancer, all enrolled at one of the three University of Washington-affiliated medical centers between 2003 to 2008. We found 2,596 probe sets differentially expressed between 167 tumor samples and 45 normal samples. Among 2,596 probe sets, 71 were significantly and consistently up- or down-regulated in the comparison between normal samples and uninvolved oral samples and between uninvolved oral samples and tumor samples. Cox regression analyses showed that 20 of the 71 probe sets were significantly associated with progression-free survival. The risk score for each patient was calculated from coefficients of a Cox model incorporating these 20 probe sets. The hazard ratio (HR) associated with each unit change in the risk score adjusting for age, gender, tumor stage, and high-risk HPV status was 2.7 (95% CI: 2.0–3.8, p = 8.8E-10). The risk scores in an independent dataset of 74 OSCC patients from the MD Anderson Cancer Center was also significantly associated with progression-free survival independent of age, gender, and tumor stage (HR 1.6, 95% CI: 1.1–2.2, p = 0.008). Gene Set Enrichment Analysis showed that the most prominent biological pathway represented by the 71 probe sets was the Integrin cell surface interactions pathway. In conclusion, we identified 71 probe sets in which dysregulation occurred in both uninvolved oral mucosal and cancer samples. Dysregulation of 20 of the 71 probe sets was associated with progression-free survival and was validated in an independent dataset.  相似文献   

9.
A decrease in the almost fifty percent mortality rate from oral cancer is needed urgently. Improvements in early diagnosis and more effective preventive treatments could affect such a decrease. Towards this end, we undertook for the first time an in-depth mass spectrometry-based quantitative shotgun proteomics study of non-invasively collected oral brush biopsies. Proteins isolated from brush biopsies from healthy normal tissue, oral premalignant lesion tissue (OPMLs), oral squamous cell carcinoma (OSCC) and matched control tissue were compared. In replicated proteomic datasets, the secretory leukocyte protease inhibitor (SLPI) protein stood out based on its decrease in abundance in both OPML and OSCC lesion tissues compared to healthy normal tissue. Western blotting in additional brushed biopsy samples confirmed a trend of gradual decreasing SLPI abundance between healthy normal and OPML tissue, with a larger decrease in OSCC lesion tissue. A similar SLPI decrease was observed in-vitro comparing model OPML and OSCC cell lines. In addition, exfoliated oral cells in patients’ whole saliva showed a loss of SLPI correlated with oral cancer progression. These results, combined with proteomics data indicating a decrease in SLPI in matched healthy control tissue from OSCC patients compared to tissue from healthy normal tissue, suggested a systemic decrease of SLPI in oral cells correlated with oral cancer development. Finally, in-vitro experiments showed that treatment with SLPI significantly decreased NF-kB activity in an OPML cell line. The findings indicate anti-inflammatory activity in OPML, supporting a mechanistic role of SLPI in OSCC progression and suggesting its potential for preventative treatment of at-risk oral lesions. Collectively, our results show for the first time the potential for SLPI as a mechanism-based, non-invasive biomarker of oral cancer progression with potential in preventive treatment.  相似文献   

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Oral squamous cell carcinoma (OSCC) is a major health problem worldwide, and patients have a particularly poor 5-year survival rate. Thus, identification of the molecular targets in OSCC and subsequent innovative therapies are greatly needed. Prolonged exposure to alcohol, tobacco, and pathogenic agents are known risk factors and have suggested that chronic inflammation may represent a potential common denominator in the development of OSCC. Microarray analysis of gene expression in OSCC cell lines with high basal NF-κB activity and OSCC patient samples identified dysregulation of many genes involved in inflammation, wound healing, angiogenesis, and growth regulation. In particular IL-8, CCL5, STAT1, and VEGF gene expression was up-regulated in OSCC. Moreover, IL-8 protein levels were significantly higher in OSCC cell lines as compared with normal human oral keratinocytes. Targeting IL-8 expression by siRNA significantly reduced the survival of OSCC cells, indicating that it plays an important role in OSCC development and/or progression. Inhibiting the inflammatory pathway by aspirin and the proteasome/NF-κB pathway by bortezomib resulted in marked reduction in cell viability in OSCC lines. Taken together our studies indicate a strong link between inflammation and OSCC development and reveal IL-8 as a potential mediator. Treatment based on prevention of general inflammation and/or the NF-κB pathway shows promise in OSCCs.  相似文献   

12.
MicroRNAs are short non-coding RNAs that regulate gene expression and are crucial to tumorigenesis. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. Up-regulation of miR-146 has been identified in OSCC tissues. However, the roles of miR-146 in carcinogenesis are controversial as it is suppressive in many other malignancies. The present study investigated the pathogenic implications of miR-146a in oral carcinogenesis. Microdissected OSCC exhibits higher levels of miR-146a expression than matched adjacent mucosal cells. The plasma miR-146a levels of patients are significantly higher than those of control subjects; these levels decrease drastically after tumor resection. miR-146a levels in tumors and in patients’ plasma can be used to classify OSCC and non-disease status (sensitivity: >0.72). Exogenous miR-146a expression is significantly increased in vitro oncogenic phenotypes as well as during xenograft tumorigenesis and OSCC metastasis. The plasma miR-146a levels of these mice parallel the xenograft tumor burdens of the mice. A miR-146a blocker abrogates the growth of xenograft tumors. miR-146a oncogenic activity is associated with down-regulation of IRAK1, TRAF6 and NUMB expression. Furthermore, miR-146a directly targets the 3′UTR of NUMB and a region within the NUMB coding sequence when suppressing NUMB expression. Exogenous NUMB expression attenuates OSCC oncogenicity. Double knockdown of IRAK1 and TRAF6, and of TRAF6 and NUMB, enhance the oncogenic phenotypes of OSCC cells. Oncogenic enhancement modulated by miR-146a expression is attenuated by exogenous IRAK1 or NUMB expression. This study shows that miR-146a expression contributes to oral carcinogenesis by targeting the IRAK1, TRAF6 and NUMB genes.  相似文献   

13.

Background

The relevance of lysophosphatidylcholine acyltransferase1 (LPCAT1), a cytosolic enzyme in the remodeling pathway of phosphatidylcholine metabolism, in oral squamous cell carcinoma (OSCC) is unknown. We investigated LPCAT1 expression and its functional mechanism in OSCCs.

Methods

We analyzed LPCAT1 mRNA and protein expression levels in OSCC-derived cell lines. Immunohistochemistry was performed to identify correlations between LPCAT1 expression levels and primary OSCCs clinicopathological status. We established LPCAT1 knockdown models of the OSCC-derived cell lines (SAS, Ca9-22) for functional analysis and examined the association between LPCAT1 expression and the platelet-activating factor (PAF) concentration and PAF-receptor (PAFR) expression.

Results

LPCAT1 mRNA and protein were up-regulated significantly (p<0.05) in OSCC-derived cell lines compared with human normal oral keratinocytes. Immunohistochemistry showed significantly (p<0.05) elevated LPCAT1 expression in primary OSCCs compared with normal counterparts and a strong correlation between LPCAT1-positive OSCCs and tumoral size and regional lymph node metastasis. In LPCAT1 knockdown cells, cellular proliferation and invasiveness decreased significantly (p<0.05); cellular migration was inhibited compared with control cells. Down-regulation of LPCAT1 resulted in a decreased intercellular PAF concentration and PAFR expression.

Conclusion

LPCAT1 was overexpressed in OSCCs and correlated with cellular invasiveness and migration. LPCAT1 may contribute to tumoral growth and metastasis in oral cancer.  相似文献   

14.
BackgroundOral squamous cell carcinoma (OSCC) remains a challenging cancer to treat despite all the advances of the last 50 years. Kallikrein 5 (KLK5) is among the serine proteases implicated in OSCC development. However, whether the activity of KLK5 promotes carcinogenesis is still controversial. Moreover, knowledge regarding the role of the KLK5 cognate inhibitor, Lympho-Epithelial Kazal-Type related Inhibitor (LEKTI), in OSCC is scarce. We have, thus, sought to investigate the importance of KLK5 and LEKTI expression in premalignant and malignant lesions of the oral cavity.MethodsKLK5 and LEKTI protein expression was evaluated in 301 human samples, which were comprised of non-malignant and malignant lesions of the oral cavity. Moreover, a bioinformatic analysis of the overall survival rate from 517 head and neck squamous cell carcinoma (HNSCC) samples was performed. Additionally, to mimic the uncovered KLK5 to serine peptidase inhibitor (SPINK5) imbalance, the KLK5 gene was abrogated in an OSCC cell line using CRISPR-Cas9 technology. The generated cell line was then used for in vivo and in vitro carcinogenesis related experiments.ResultsLEKTI was found to be statistically downregulated in OSCCs, with increased KLK5/SPINK5 mRNA ratio being associated with a shorter overall survival (p=0.091). Indeed, disruption of KLK5 to SPINK5 balance through the generation of KLK5 null OSCC cells led to smaller xenografted tumors and statistically decreased proliferation rates following multiple time points of BrdU treatment in vitro.ConclusionThe association of increased enzyme/inhibitor ratio with poor prognosis indicates KLK5 to SPINK5 relative expression as an important prognostic marker in OSCC.  相似文献   

15.
Objective: To qualitative and quantitatively review published literature assessing the oxidative stress marker malondialdehyde (MDA) in oral squamous cell carcinoma (OSCC). Methodology: Pubmed (MeSH), Science Direct, Scopus, Web of Science, Willey Online Library, Cochrane, and Cross Reference were searched for studies assessing MDA levels in OSCC samples. Results: From the 1008 articles identified, 849 were excluded based on title and abstract screening due to duplication and irrelevance to the topic of interest. Full-text assessment of the remaining 159 articles led to the inclusion of only 46 articles that satisfied the selection criteria. Of these, only 26 studies had data compatible for quantitative analysis. The MDA levels in OSCC groups are significantly increased (p < 0.00001) in plasma, serum, and saliva samples in the majority of the studies evaluated. In contrast, MDA levels in OSCC tissue samples are significantly attenuated (p < 0.00001) compared to healthy controls, supported by fewer studies. Conclusions: The augmented MDA levels in plasma, serum, and saliva samples of the OSCC reflect the heightened oxidative stress level accurately. Further studies are required to understand the attenuated MDA levels in the tissue samples of OSCC. Correlation analysis between MDA levels with established clinicopathological prognostic markers could aid in formulating oxidative stress-based prognostication and treatment planning.  相似文献   

16.
ObjectiveTo evaluate the in situ antiplaque effect after 4 days of using of 2 commercial antimicrobial agents in short term on undisturbed plaque-like biofilm.InterventionThe participants wore an appliance in 3 different rinsing periods doing mouthwashes twice a day (1/0/1) with essential oils, 0.2% chlorhexidine or sterile water (negative control). At the end of each 4-day mouthwash period, samples were removed from the appliance. Posteriorly, after bacterial vital staining, samples were analysed using a Confocal Laser Scanning Microscope.ResultsThe essential oils and the 0.2% chlorhexidine were significantly more effective than the sterile water at reducing bacterial vitality, thickness and covering grade by the biofilm. No significant differences were found between the 0.2% chlorhexidine and the essential oils at reducing the bacterial vitality (13.2% vs. 14.7%). However, the 0.2% chlorhexidine showed more reduction than the essential oils in thickness (6.5 μm vs. 10.0 μm; p<0.05) and covering grade by the biofilm (20.0% vs. 54.3%; p<0.001).ConclusionThe essential oils and 0.2% chlorhexidine showed a high antiplaque effect. Although the 0.2% chlorhexidine showed better results with regard to reducing the thickness and covering grade by the biofilm, both antiseptics showed a high and similar antibacterial activity.

Clinical Relevance

Daily essential oils or 0.2% chlorhexidine mouthwashes are effective when reducing dental plaque formation in the short term. Although 0.2% chlorhexidine continues to be the “gold standard” in terms of antiplaque effect, essential oils could be considered a reliable alternative.

Trial Registration

ClinicalTrials.gov NCT02124655  相似文献   

17.
目的:探讨分析MACC1和C-Met在正常口腔黏膜、口腔白斑及口腔鳞状细胞癌中的表达及其临床意义。方法:采用免疫组化SP法检测20例口腔黏膜、20例上皮异常增生白斑、50例口腔鳞癌组织中的MACC1、C-Met蛋白的表达情况,采用X2和spearman等级相关分析对结果进行判定。结果:MACC1、C-Met蛋白在异常增生型白斑和口腔鳞癌中的阳性表达率分别为50%、76%,35%、66%,均明显高于正常口腔黏膜(17.6%,5.0%),差异均有统计学意义(P0.05)。MACC1和C-Met蛋白表达与口腔鳞癌的分期、淋巴结转移及分化程度密切相关(P0.05)。Spearman等级相关分析显示口腔白斑及口腔鳞癌中MACC1和C-Met的表达呈现正相关(P0.05)。结论:MACC1和C-Met在上皮不典型增生性白斑和口腔鳞癌中高表达,二者在口腔黏膜白斑的癌变和口腔鳞癌的发生发展中可能起重要作用。  相似文献   

18.
We sought to evaluate in this study the significance of cytokeratin (CK)-19 and CK-20 in determining the peritoneal micrometastasis of gastric carcinoma and also determine the factors related with the occurrence of peritoneal micrometastasis. For this purpose, 152 patients with gastric cancer were enrolled in the study and transverse mesocolon biopsies were undertaken intraoperatively. The CK19 and CK20 immunohistochemical staining were performed on the tissue samples, and the results were compared with those of H&E staining and peritoneal lavage cytology (PLC). Our data show that the positivity rates of CK19 and CK20 in transverse mesocolon were 48.6 and 61.2%, respectively, which were significantly higher (P < 0.05) than that (10.0%) of PLC. Besides, the positivity rate increased with the depth of tumor invasion. Based on these data, we concluded that CK19 and CK20 expressions could be adopted to determine the peritoneal micrometastasis for accurate clinical staging of the patients. These data provide reliable guideline for postoperative treatment and prognosis of gastric carcinoma.  相似文献   

19.
Background: Oral leukoplakia is one of the most common oral premalignant disorder. The classical evaluation through tissue biopsy is not always valid to evaluate the risk of malignization.

Material and methods: RT-qPCR was performed on 47 blood samples (21 patients with leukoplakia, 2 with oral squamous cell carcinoma (OSCC), and 24 healthy patients) and on 11 tissue samples (3 leukoplakia, 4 OSCC, and 4 samples of healthy tissue).

Results: There are significant differences in expression between the different groups (F?=?4.057, p?=?.006). The Duncan post hoc test shows that the only group that differentiates is the tumour tissue. Using Wilcoxon test, different covariables of patients with leukoplakia were analysed with respect to the group of healthy patients and no significant differences were observed.

Conclusions: The diagnostic route through liquid biopsy has not been conclusive in this study, but there are significant differences in the levels analysed in the different tissue samples.  相似文献   

20.
目的:探讨磷脂酶Cε1(PLCE1)与基质金属蛋白酶-9(MMP-9)在口腔鳞癌中的表达及临床意义。方法:采用免疫组化方法检测61例口腔鳞癌组织和35例正常口腔黏膜组织中PLCE1和MMP-9的蛋白表达,并分析二者与口腔鳞状细胞癌临床病理参数的关系及二者的相关性。结果:PLCE1在口腔鳞癌组织中表达阳性率为68.85%(42/61),MMP-9在口腔鳞癌组织中表达阳性率为75.40%(46/61),两者在正常口腔黏膜组织中表达阳性率分别为14.28%(5/35)、17.14%(6/35)。PLCE1和MMP-9在正常口腔黏膜组织的阳性表达率均明显低于口腔鳞癌组织(P0.01)。PLCE1与MMP-9的高度阳性表达和患者的性别、年龄、吸烟及肿瘤大小无明显相关性,但与肿瘤TNM分期以及组织分化程度显著相关。口腔鳞癌组织中PLCE1和MMP-9的高表达呈明显正相关(r=0.438,P0.01)。结论:PLCE1和MMP-9的过度表达均与口腔鳞癌的发生、发展及侵袭转移有密切相关性,并检测二者可能会对口腔鳞癌患者的早期临床诊断及预后判断具有一定的参考价值。  相似文献   

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