Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected indi...Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.展开更多
Background: To investigate the therapeutic activity of the miR-221/222 inhibitor against OSCC in vitro and in vivo. Materials and Methods: HSC3 and HSC6 were treated with miR-221/222 inhibitor and the empty vector res...Background: To investigate the therapeutic activity of the miR-221/222 inhibitor against OSCC in vitro and in vivo. Materials and Methods: HSC3 and HSC6 were treated with miR-221/222 inhibitor and the empty vector respectively. After the recombinants were transfected into HSC3 and HSC6 with Lipofectamine<sup>TM</sup> MAX, the expression of miR-221/222 and PUMA was analyzed by RT-PCR. The proliferation and migration of HSC3 and HSC6 were detected by CCK-8 assay and Wound-healing assay. Cell cycle and apoptosis were detected by flow cytometry. The effect of the miR-221/222 inhibitor was also assessed in OSCC xenografts in BALB/c-nu mice. Results: Transfection of the miR-221/222 inhibitor increased cell apoptosis and upregulated PUMA expression in OSCC cell lines HSC3 and HSC6 with the significantly reduced expression of miR-221 and miR-222. Furthermore, the miR-221/222 inhibitor suppressed cell growth and invasion and blocked the cell cycle at the G1 phase. Obvious anti-tumor activity was achieved in BALB/c-nu mice by treatment with the miR-221/222 inhibitor, together with the upregulation of PUMA protein in tumors retrieved from the mice. Conclusions: There was a significant inhibitory effect of the miR-221/222 inhibitor on the growth of OSCC both in vitro and in vivo, and there might be a regulatory loop between miR-221/222 and PUMA. These findings demonstrated that downregulation of miR-221/222 could induce cell apoptosis, and it might be considered as a candidate target for gene therapy of OSCC.展开更多
Objective Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck,but its occurrence and progression mechanisms remain unclear.In addition-there is a lack of effective targeting drugs...Objective Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck,but its occurrence and progression mechanisms remain unclear.In addition-there is a lack of effective targeting drugs.The second major subunit of DNA polymerase(POLE2)catalyzes the prolongation of new strand replication and modifies exonuclease domain activity.Our previous study found that POLE2 was associated with OSCC progression,but the mechanism remains unclear.Methods The expression of POLE2 in OSCC tissues was detected using immunological assays.Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC.POLE2 expression was inhibited in OSCC cells,and the effects of gene and protein expression were detected using RT-PCR and Western blotting.The POLE2 knockout model was constructed by transfecting a lentiviral vector.Cell proliferation,apoptosis,and migration were detected using various assays including colony formation,MTT,flow cytometry,wound healing assay,Transwell assay,and the Human Apoptosis Antibody Array.The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice.After 30 days,tumors were removed under anesthesia and tumor weight and dimension were recorded.Tumor cell proliferation was analyzed using Ki67 staining.Results POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues.In addition,POLE2 gene levels were statistically correlated with tumor classification and prognosis.Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro.Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation.We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3,CD40,CD40L,DR6,Fas,IGFBP-6,p21,and SMAC.In addition,POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway.Conclusion POLE2 is closely related to the progression of OSCC.Thus,POLE2 may be a potential target for OSCC treatment.展开更多
Objective:To investigate the effect of interleukin 6/Janus kinase 2/signal transducer and activator of transcription 3(IL-6/JAK2/STAT3)on the biological behavior of oral squamous cell carcinoma(OSCC).Methods:OSCC cell...Objective:To investigate the effect of interleukin 6/Janus kinase 2/signal transducer and activator of transcription 3(IL-6/JAK2/STAT3)on the biological behavior of oral squamous cell carcinoma(OSCC).Methods:OSCC cells were transfected with the designed lentiviral vector plasmid pGMLV-SB3(experimental group)and the corresponding negative control plasmid pGMLV-SB3-shNC(control group);48 hours after transfection,a liposome transfection kit(Sigma,USA)was used for lentivirus packaging;after virus packaging,a medium containing pGMLV-SB3 lentiviral vector was added and cultured for 24 h;the cells were harvested,and RNA was extracted;Transwell chamber assay(Sigma,USA)was used to detect cell migration and invasion ability;dot-enzyme-linked immunosorbent assay(ELISA)kit was used to detect the level of interleukin 6(IL-6)in the culture supernatant,while serum IL-6 level was measured by ELISA.Results:The expressions of IL-6,JAK2,and STAT3 in the experimental group were significantly raised,as compared to the control group(P<0.05);the apoptosis rate of OSCC cells in the experimental group,which was detected by flow cytometry 48 h after transfection,was significantly higher than that of cells in the control group(P<0.05);and there was a significant improvement in the experimental group’s cell migration and invasion ability,as compared to that of the control group(P<0.05).Conclusion:The IL-6/JAK2/STAT3 signaling pathway plays an important role in the migration and invasion of OSCC cells.Inhibiting the expression of IL-6 can inhibit the growth and proliferation of OSCC cells as well as reduce their ability to invade and migrate.These results provide a new target for the treatment of OSCC.展开更多
Objective:To investigate the effect of MMP-9 inhibitor(Mki67)on the biology of human oral squamous cell carcinoma SCC15 cell line and to explore its mechanism of action through PI3K/Akt signaling pathway.Methods:SCC15...Objective:To investigate the effect of MMP-9 inhibitor(Mki67)on the biology of human oral squamous cell carcinoma SCC15 cell line and to explore its mechanism of action through PI3K/Akt signaling pathway.Methods:SCC15 cells were extracted,and the supernatant was discarded.The cells were then rinsed twice with PBS,and 0,2.5,5,and 10μL of Mki67(50 mg/mL)were added to the culture respectively.The inhibition rate of cell proliferation was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide(MTT)method,and the cell migration was measured by Transwell chamber test.The cell apoptosis rate was detected by cytometry,and the p-Akt protein content in the cells of each group was determined by a double-antibody sandwich enzyme-linked immunosorbent assay(ELISA)kit.Results:The cell proliferation rates of the 2.5μL,5μL,and 10μL dose groups were all lower than the 0μL group(P<0.05)before treatment,and the cell proliferation rates in the 2.5μL,5μL,and 10μL dose groups decreased overtime(P<0.05).After 24 h,with the increase of Mki67 concentration,the number of migration and invasion gradually decreased(P<0.05),and the number of apoptosis gradually increased(P<0.05);besides,the relative expression of MMP-9,PI3K,and Akt mRNA decreased gradually(P<0.05),and the expression level of Akt mRNA was not statistically significant(P>0.05).Conclusion:MMP-9 inhibitor(Mki67)can inhibit the proliferation and migration of SCC15 cell line and induce apoptosis,and its mechanism of action may be related to the inhibition of PI3K/Akt signaling pathway.展开更多
Oral squamous cell carcinoma is a challenging oncology problem.A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined.Using quantitative immunohistochemistry,we examined t...Oral squamous cell carcinoma is a challenging oncology problem.A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined.Using quantitative immunohistochemistry,we examined the expression of vimentin,E-cadherin,and beta-catenin in 83 oral squamous cell carcinoma patients,and the relationships between the expression of these markers and specific clinicopathological features were analysed.The high expression of vimentin was observed in 23 of 43(53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death(P < 0.001 and < 0.001,respectively).The decreased expression of E-cadherin was observed in 36 of 43(84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death(P < 0.001 and < 0.001,respectively).Although no correlation between beta-catenin expression in whole-tumour sections and clinicopathological features was observed,decreased beta-catenin expression at the tumour invasive front was closely associated with recurrence and death(P=0.002 and 0.002,respectively).The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses.Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients.The combination of the upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma.展开更多
Objective: The management of early-stage(cT1/2N0) oral squamous cell carcinoma(OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation(OBS) and elective neck...Objective: The management of early-stage(cT1/2N0) oral squamous cell carcinoma(OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation(OBS) and elective neck dissection(END) in treating patients with cT1/2N0 OSCC.Methods: A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival(OS), diseasespecific survival(DSS), and recurrence-free survival(RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test.Results: There was no significant difference in 5-year OS and DSS rates between END and OBS groups(OS:89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group(90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group(7/51) had similar 5-year OS rate(57.1% vs. 64.1%, P=0.839) and DSS rate(71.4% vs. 74.4%, P=0.982) to those in END group(39/181). In the regional recurrence patients, the 5-year OS rate(57.1% vs. 11.1%, P=0.011) and DSS rate(71.4% vs. 22.2%, P=0.022) in OBS group(7/51) were higher than those in END group(9/181).Conclusions: The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.展开更多
Honokiol (HNK) is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma (OSCC) cells ...Honokiol (HNK) is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma (OSCC) cells is unknown. We investigated the antitumor activities of HNK on OSCC cells in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and propidium iodide (PI) assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling (TUNEL), and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 μg·mL-1 or 20 μg·mL-1 of HNK were more stronger compared with those of 20 μg·mL-1 5-fluorouracil (5-Fu, the control) applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.展开更多
Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated wit...Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.展开更多
Oral squamous cell carcinoma(OSCC) is a common malignant tumor of the head and neck, and recurrence is an important prognostic factor in patients with OSCC. We explored the factors associated with recurrence of OSCC a...Oral squamous cell carcinoma(OSCC) is a common malignant tumor of the head and neck, and recurrence is an important prognostic factor in patients with OSCC. We explored the factors associated with recurrence of OSCC and analyzed the survival of patients after recurrence. Clinicopathologic and follow-up data of 275 patients with OSCC treated by surgery in the Cancer Institute and Hospital of Tianjin Medical University between 2002 and 2006 were analyzed. Recurrence factors were analyzed with Chisquare or Fisher′s exact test and multivariate analysis. The prognosis of patients after recurrence was analyzed with the Kaplan-Meier method and log-rank test. The recurrence rate was 32.7%. The recurrence time ranged from 2 to 96 months, with a median of 14 months. Univariate analysis showed that T stage, degree of differentiation, pN stage, flap application, resection margin, and lymphovascular invasion were factors of recurrence (P<0.05). Multivariate analysis showed that T stage, degree of differentiation, and pN stage were independent factors of recurrence (P<0.001). The differences in gender, age, tumor site, region of lymph node metastasis, and perineural invasion between the recurrence and non-recurrence groups were not significant (P>0.05). Kaplan-Meier and log-rank tests showed that the 2- and 5-year survival rates were significantly lower in the recurrence group than in non-recurrence group(67.6% vs. 88.0%, 31.8% vs. 79.9%, P<0.001). Therefore, to improve prognosis, we recommend extended local excision, flap, radical neck dissection, and adjuvant chemoradiotherapy for patients more likely to undergo recurrence.展开更多
The aim of the study was a determination of the levels of nitric oxide(NO)and its biological markers such as malonyldialdehyde(MDA)and nitrotyrosine in the serum of patients with squamous cell carcinoma(SCC)of the ora...The aim of the study was a determination of the levels of nitric oxide(NO)and its biological markers such as malonyldialdehyde(MDA)and nitrotyrosine in the serum of patients with squamous cell carcinoma(SCC)of the oral cavity and identification of the relationships between NO and those markers.These studies were performed on patients with SCC of the oral cavity before and after treatment.Griess reaction was used for the estimation of the total concentration of NO in serum.The nitrotyrosine level in serum was assessed with an enzyme-linked immunosorbent assay(ELISA)kit,and MDA level using a spectrophotometric assay.Higher concentrations of NO in blood serum were determined in patients with stage IV of the disease before treatment in comparison to the control group and patients with stages II and III of the disease.Moreover,higher concentrations of MDA and nitrotyrosine were determined in the serum of patients in all stages of the disease in comparison to healthy people.After treatment,lower concentrations of NO in the serum of patients with stage IV of the disease were observed in comparison to the amounts obtained prior to treatment.In addition,lower levels of nitrotyrosine in the serum of patients with all stages of the disease were recorded,whereas higher concentrations of MDA were determined in these patients in comparison to results obtained before treatment.The compounds formed with the contribution of NO,such as MDA and nitrotyrosine,may lead to cancer progression in patients with SCC of the oral cavity,and contribute to formation of resistance to therapy in these patients as well.Moreover,the lack of a relationship between concentrations of NO and MDA,and between NO and nitrotyrosine in serum suggests that the process of lipid peroxidation and nitration in patients with SCC does not just depend on NO.展开更多
Although a few studies have shown that vascularity is increased from normal mucosa to dysplasia to carcinoma suggesting that disease progression in the oral mucosa is accompanied by angiogenesis. The role in lymph nod...Although a few studies have shown that vascularity is increased from normal mucosa to dysplasia to carcinoma suggesting that disease progression in the oral mucosa is accompanied by angiogenesis. The role in lymph node metastasis in oral squamous cell carcinoma (OSCC) is equivocal. Role of angiogenesis in OSCC development and metastasis is evaluated in this study. This retrospective study of 50 samples consisted of 9 normal buccal mucosa, 22 leukoplakias, and 19 OSCC. Polyclonal antibodies to von-Willebrand factor were used to highlight the microvessels. Images were captured and morphometric image analysis was done for microvessel density (MVD), area, and perimeter. Highest, as well as mean values of these three parameters were compared. MVD and perimeter, but not area, are significantly different between normal mucosa and OSCC, and leukoplakia and OSCC. There were no differences between normal mucosa and leukoplakia. MVD, area, and perimeter were not significantly different between the OSCC with and without lymph node metastasis. The highest and mean values of MVD are significantly correlated. In the development of OSCC, angiogenic phenotypic change occurs in carcinomas rather than in the pre-cancerous stage, and quantification of angiogenesis in OSCC does not predict the risk of lymph node metastasis.展开更多
Objective:This study aimed to examine a novel method for prognostic evaluation of patients with oral squamous cell carcinoma(OSCC)based on the expression of heterogeneous nuclear ribonucleoprotein C(HNRNPC),YTH domain...Objective:This study aimed to examine a novel method for prognostic evaluation of patients with oral squamous cell carcinoma(OSCC)based on the expression of heterogeneous nuclear ribonucleoprotein C(HNRNPC),YTH domain-binding protein 2(YTHDF2),and methyltransferase 14(METTL14).Methods:We obtained the RNA sequence and clinical information of OSCC patients from The Cancer Genome Atlas database.An optical method was established by the least absolute shrinkage and selection operator Cox regression algorithm,which was used to calculate the risk score of every sample.In addition,all samples(n=239)were classified into high-risk(n=119)and low-risk(n=120)groups,and the overall survival(OS)time and clinical characteristics were compared between groups.Moreover,bioinformatics analysis was carried out.Gene set enrichment analysis was performed to investigate the signaling pathways of HNRNPC,YTHDF2,and METTL14.Results:The two groups showed significantly different OS time,tumor grades,tumor stages,and pathologic T stages(P<0.05).The receiver operating characteristic analysis identified that our method was effective and it was more accurate than use of age,gender,tumor grade,tumor stage,pathologic T stage,and pathologic N stage in OSCC prognostic prediction.Gene set enrichment analysis revealed that HNRNPC,YTHDF2,and METTL14 were mainly associated with ubiquitin-mediated proteolysis,cell cycle,RNA degradation,and spliceosome signaling pathways.Conclusion:The method based on the expression of HNRNPC,YTHDF2,and METTL14 can predict the prognosis of patients with OSCC independently,and its prognostic value is better than that of clinicopathological characteristic indicators.展开更多
Objective: To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer. Metho...Objective: To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer. Methods: The immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC. Results: The expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) ( P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) ( P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM ( P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP ( P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM ( P<0.01). The COX-2 expression was associated with clinical stage ( P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis ( P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC. Conclusions: The abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.展开更多
Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of huma...Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of human solid tumors. We sought to determine the effects of Cordycepin on oral squamous cell carcinoma in vitro and in vivo. Two oral squamous cell carcinoma cell lines, KB and HSC3, were used in this study. Cells were treated with Cordycepin or diluent, followed by determinations of proliferation by sulforhodamine method and apoptosis by TUNEL assay in vitro. For in vivo experiments, tumor cells were transplanted into nude mice, followed by treatment with Cordycepin or control diluent. In addition, cells were examined for expression of adenosine receptor isotypes, and tested whether cordycepin-induced effects were mediated through adenosine receptors by combinatorial treatment of cordycepin and antagonists specific to each isotype of adenosine receptors. Two cell lines expressed protein of all types of adenosine receptors stronger than normal oral keratinocytes. Cordycepin showed anti-proliferating effect and apoptotic effect on both cell lines in vitro in a dose dependent manner. However, any adenosine receptors did not reverse the effect of cordycepin. In our in vivo experiments, cordycepin failed to decrease the tumor volume significantly, and failed to induce more apoptosis of tumor cells. Cordycepin has anti-proliferating effect and induces apoptosis not mediated by adenosine receptor on oral squamous cell carcinoma cells in vitro. However, in vivo results suggest that cordycepin in itself has a limited value as a novel chemotherapeutic agent for oral squamous cell carcinoma.展开更多
Oral squamous cell carcinoma is a neoplasm that originates from the epithelial mucosa.It is usually more frequent between the fifth and sixth decades of life,and more than 90% of carcinomas of the oral cavity are squa...Oral squamous cell carcinoma is a neoplasm that originates from the epithelial mucosa.It is usually more frequent between the fifth and sixth decades of life,and more than 90% of carcinomas of the oral cavity are squamous cell carcinoma.It is an invasive neoplasia with a significant recurrence rate;40% of patients present with metastases in the cervical lymph nodes at the time of diagnosis.The tumor invasion front is a characteristic of tumor growth,which can be infiltrative or noninvasive.The histopathological parameters examined include the number of mitoses,depth of the tumor,invasion pattern,degree of keratinization,and nuclear pleomorphism.For the pathologist,these parameters are routinely evaluated but are not reported to the treating physician in all cases,which we consider to be useful information when determining the therapeutic route.展开更多
iASPP is an inhibitory member of the apoptosis-stimulating proteins of P53(ASPP) family. iASPP is over expressed in several malignant tumors and potentially affects cancer progression. However, the expression and pote...iASPP is an inhibitory member of the apoptosis-stimulating proteins of P53(ASPP) family. iASPP is over expressed in several malignant tumors and potentially affects cancer progression. However, the expression and potential role of iASPP in oral tongue squamous cell carcinoma(OTSCC) have not been addressed. In our study, we detected iASPP expression in OTSCC by immunohistochemistry. iASPP expression is up-regulated in OTSCC tissues. Moreover, in clinical pathology specimens, we found that increased iASPP expression correlates with poor differentiation and lymph node metastasis. Using multicellular tumor spheroids(MTS) and flow cytometry, we demonstrated that iASPP down-regulation arrests OTSCC cells at the G0/G1 phase, induces OTSCC cell apoptosis and inhibits OTSCC cell proliferation. These results indicate that iASPP plays a significant role in the progression of OTSCC and may serve as a biomarker or therapeutic target for OTSCC patients.展开更多
Objective Several studies have revealed the critical role of long non-coding RNAs(lncRNAs)as biomarkers for diagnosing oral squamous cell carcinoma(OSCC).However,the data remain inconsistent.This meta-analysis was per...Objective Several studies have revealed the critical role of long non-coding RNAs(lncRNAs)as biomarkers for diagnosing oral squamous cell carcinoma(OSCC).However,the data remain inconsistent.This meta-analysis was performed to summarize the potential of lncRNAs as OSCC biomarkers.Methods We searched PubMed,Cochrane Library,Web of Science,and China National Knowledge Infrastructure databases for literature published until December 10,2020.Study quality was assessed using Quality Assessment for Studies of Diagnostic Accuracy-2,and sensitivity,specificity,and other measures regarding lncRNAs for OSCC diagnosis were pooled using bivariate meta-analysis models.Data analyses were performed using STATA 14.0.Results Overall,8 studies with 981 cases and 585 controls were included in the pooled analysis.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic odds ratio,and area under the receiver operating characteristic curve values were as follows:0.76[95%confidence interval(CI),0.65–0.84],0.90(95%CI,0.82–0.95),7.5(95%CI,4.20–13.40),0.27(95%CI,0.18–0.39),28(95%CI,13.00–58.00),0.90(95%CI,0.87–0.93),respectively.Deeks’funnel plot asymmetry test(P=0.56)indicated no potential publication bias.Conclusion Our meta-analytical evidence suggests that lncRNAs could be employed as a potential non-invasive diagnostic tool for OSCC.展开更多
Squamous cell carcinoma accounts for 90% of all oral cancers. It may affect any anatomical site in the mouth, but most commonly the tongue and the floor of the mouth. It usually arises from a pre-existing potentially ...Squamous cell carcinoma accounts for 90% of all oral cancers. It may affect any anatomical site in the mouth, but most commonly the tongue and the floor of the mouth. It usually arises from a pre-existing potentially malignant lesion, and occasionally de novo;but in either case from within a field of precancerized epithelium. The use of tobacco and betel quid, heavy drinking of alcoholic beverages and a diet low in fresh fruits and vegetables are well known risk factors for oral squamous cell carcinoma. Important risk factors related to the carcinoma itself that are associated with a poor prognosis include large size of the tumour at the time of diagnosis, the presence of metastases in regional lymphnodes, and a deep invasive front of the tumour. Squamous cell carcinoma is managed by surgery, radiation, and chemotherapy singularly or in combination;but regardless of the treatment modality, the five-year survival rate is poor at about 50%. This can be attributed to the fact that about two-thirds of persons with oral squamous cell carcinoma already have a large lesion at the time of diagnosis.展开更多
Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral c...Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases (CLNM) in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy (aRT) and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.展开更多
文摘Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.
文摘Background: To investigate the therapeutic activity of the miR-221/222 inhibitor against OSCC in vitro and in vivo. Materials and Methods: HSC3 and HSC6 were treated with miR-221/222 inhibitor and the empty vector respectively. After the recombinants were transfected into HSC3 and HSC6 with Lipofectamine<sup>TM</sup> MAX, the expression of miR-221/222 and PUMA was analyzed by RT-PCR. The proliferation and migration of HSC3 and HSC6 were detected by CCK-8 assay and Wound-healing assay. Cell cycle and apoptosis were detected by flow cytometry. The effect of the miR-221/222 inhibitor was also assessed in OSCC xenografts in BALB/c-nu mice. Results: Transfection of the miR-221/222 inhibitor increased cell apoptosis and upregulated PUMA expression in OSCC cell lines HSC3 and HSC6 with the significantly reduced expression of miR-221 and miR-222. Furthermore, the miR-221/222 inhibitor suppressed cell growth and invasion and blocked the cell cycle at the G1 phase. Obvious anti-tumor activity was achieved in BALB/c-nu mice by treatment with the miR-221/222 inhibitor, together with the upregulation of PUMA protein in tumors retrieved from the mice. Conclusions: There was a significant inhibitory effect of the miR-221/222 inhibitor on the growth of OSCC both in vitro and in vivo, and there might be a regulatory loop between miR-221/222 and PUMA. These findings demonstrated that downregulation of miR-221/222 could induce cell apoptosis, and it might be considered as a candidate target for gene therapy of OSCC.
基金the National Natural Science Foundation of China(No.82203418)the Natural Science Foundation of Hubei Province(No.2022CFB286 and No.2021CFB589).
文摘Objective Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck,but its occurrence and progression mechanisms remain unclear.In addition-there is a lack of effective targeting drugs.The second major subunit of DNA polymerase(POLE2)catalyzes the prolongation of new strand replication and modifies exonuclease domain activity.Our previous study found that POLE2 was associated with OSCC progression,but the mechanism remains unclear.Methods The expression of POLE2 in OSCC tissues was detected using immunological assays.Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC.POLE2 expression was inhibited in OSCC cells,and the effects of gene and protein expression were detected using RT-PCR and Western blotting.The POLE2 knockout model was constructed by transfecting a lentiviral vector.Cell proliferation,apoptosis,and migration were detected using various assays including colony formation,MTT,flow cytometry,wound healing assay,Transwell assay,and the Human Apoptosis Antibody Array.The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice.After 30 days,tumors were removed under anesthesia and tumor weight and dimension were recorded.Tumor cell proliferation was analyzed using Ki67 staining.Results POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues.In addition,POLE2 gene levels were statistically correlated with tumor classification and prognosis.Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro.Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation.We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3,CD40,CD40L,DR6,Fas,IGFBP-6,p21,and SMAC.In addition,POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway.Conclusion POLE2 is closely related to the progression of OSCC.Thus,POLE2 may be a potential target for OSCC treatment.
文摘Objective:To investigate the effect of interleukin 6/Janus kinase 2/signal transducer and activator of transcription 3(IL-6/JAK2/STAT3)on the biological behavior of oral squamous cell carcinoma(OSCC).Methods:OSCC cells were transfected with the designed lentiviral vector plasmid pGMLV-SB3(experimental group)and the corresponding negative control plasmid pGMLV-SB3-shNC(control group);48 hours after transfection,a liposome transfection kit(Sigma,USA)was used for lentivirus packaging;after virus packaging,a medium containing pGMLV-SB3 lentiviral vector was added and cultured for 24 h;the cells were harvested,and RNA was extracted;Transwell chamber assay(Sigma,USA)was used to detect cell migration and invasion ability;dot-enzyme-linked immunosorbent assay(ELISA)kit was used to detect the level of interleukin 6(IL-6)in the culture supernatant,while serum IL-6 level was measured by ELISA.Results:The expressions of IL-6,JAK2,and STAT3 in the experimental group were significantly raised,as compared to the control group(P<0.05);the apoptosis rate of OSCC cells in the experimental group,which was detected by flow cytometry 48 h after transfection,was significantly higher than that of cells in the control group(P<0.05);and there was a significant improvement in the experimental group’s cell migration and invasion ability,as compared to that of the control group(P<0.05).Conclusion:The IL-6/JAK2/STAT3 signaling pathway plays an important role in the migration and invasion of OSCC cells.Inhibiting the expression of IL-6 can inhibit the growth and proliferation of OSCC cells as well as reduce their ability to invade and migrate.These results provide a new target for the treatment of OSCC.
文摘Objective:To investigate the effect of MMP-9 inhibitor(Mki67)on the biology of human oral squamous cell carcinoma SCC15 cell line and to explore its mechanism of action through PI3K/Akt signaling pathway.Methods:SCC15 cells were extracted,and the supernatant was discarded.The cells were then rinsed twice with PBS,and 0,2.5,5,and 10μL of Mki67(50 mg/mL)were added to the culture respectively.The inhibition rate of cell proliferation was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide(MTT)method,and the cell migration was measured by Transwell chamber test.The cell apoptosis rate was detected by cytometry,and the p-Akt protein content in the cells of each group was determined by a double-antibody sandwich enzyme-linked immunosorbent assay(ELISA)kit.Results:The cell proliferation rates of the 2.5μL,5μL,and 10μL dose groups were all lower than the 0μL group(P<0.05)before treatment,and the cell proliferation rates in the 2.5μL,5μL,and 10μL dose groups decreased overtime(P<0.05).After 24 h,with the increase of Mki67 concentration,the number of migration and invasion gradually decreased(P<0.05),and the number of apoptosis gradually increased(P<0.05);besides,the relative expression of MMP-9,PI3K,and Akt mRNA decreased gradually(P<0.05),and the expression level of Akt mRNA was not statistically significant(P>0.05).Conclusion:MMP-9 inhibitor(Mki67)can inhibit the proliferation and migration of SCC15 cell line and induce apoptosis,and its mechanism of action may be related to the inhibition of PI3K/Akt signaling pathway.
文摘Oral squamous cell carcinoma is a challenging oncology problem.A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined.Using quantitative immunohistochemistry,we examined the expression of vimentin,E-cadherin,and beta-catenin in 83 oral squamous cell carcinoma patients,and the relationships between the expression of these markers and specific clinicopathological features were analysed.The high expression of vimentin was observed in 23 of 43(53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death(P < 0.001 and < 0.001,respectively).The decreased expression of E-cadherin was observed in 36 of 43(84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death(P < 0.001 and < 0.001,respectively).Although no correlation between beta-catenin expression in whole-tumour sections and clinicopathological features was observed,decreased beta-catenin expression at the tumour invasive front was closely associated with recurrence and death(P=0.002 and 0.002,respectively).The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses.Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients.The combination of the upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma.
基金supported by grants from National Natural Science Foundation of China (No. 81372884 and No. 81672679)5010 Project of Clinical Study, Sun Yat-sen University (No. 2010018)
文摘Objective: The management of early-stage(cT1/2N0) oral squamous cell carcinoma(OSCC) remains a controversial issue. The aim of this study was to compare the clinical outcomes of neck observation(OBS) and elective neck dissection(END) in treating patients with cT1/2N0 OSCC.Methods: A total of 232 patients with cT1/2N0 OSCC were included in this retrospective study. Of these patients, 181 were treated with END and 51 with OBS. The survival curves of 5-year overall survival(OS), diseasespecific survival(DSS), and recurrence-free survival(RFS) rates were plotted using the Kaplan-Meier method for each group, and compared using the Log-rank test.Results: There was no significant difference in 5-year OS and DSS rates between END and OBS groups(OS:89.0% vs. 88.2%, P=0.906; DSS: 92.3% vs. 92.2%, P=0.998). However, the END group had a higher 5-year RFS rate than the OBS group(90.1% vs. 76.5%, P=0.009). Patients with occult metastases in OBS group(7/51) had similar 5-year OS rate(57.1% vs. 64.1%, P=0.839) and DSS rate(71.4% vs. 74.4%, P=0.982) to those in END group(39/181). In the regional recurrence patients, the 5-year OS rate(57.1% vs. 11.1%, P=0.011) and DSS rate(71.4% vs. 22.2%, P=0.022) in OBS group(7/51) were higher than those in END group(9/181).Conclusions: The results indicated that OBS policy could obtain the same 5-year OS and DSS as END. Under close follow-up, OBS policy may be an available treatment option for patients with clinical T1/2N0 OSCC.
基金supported by grants from the National Science Funds for Talented Professionals of China (No. 30725041)the National Natural Science Foundation of China (No. 30930100, 30672323, 81072218)+1 种基金State Key Laboratory of Oral Diseases Open Funding (SKLODOF 2010-01) of Chinathe Changjiang Professorship Support Program of Ministry of Education, China
文摘Honokiol (HNK) is a small organic molecule purified from magnolia species and has demonstrated anticancer activities in a variety of cancer cell lines; however, its effect on oral squamous cell carcinoma (OSCC) cells is unknown. We investigated the antitumor activities of HNK on OSCC cells in vitro for the first time. The inhibitory effects of HNK on the growth and proliferation of OSCC cells were demonstrated via in vitro 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and propidium iodide (PI) assays, and the apoptotic cells were investigated by the observation of morphological changes and detection of DNA fragmentation via PI, TdT-mediated dUTP-biotin nick end labeling (TUNEL), and DNA ladder assays, as well as flow cytometry assay. The results showed that HNK inhibited the growth and proliferation of OSCC cells in vitro in a time and dose-dependent manner. The inhibitory effect was associated with the cell apoptosis induced by HNK, evidenced by the morphological features of apoptotic cells, TUNEL-positive cells and a degradation of chromosomal DNA into small internucleosomal fragments. The study also demonstrated here that the inhibition or apoptosis mediated by 15 μg·mL-1 or 20 μg·mL-1 of HNK were more stronger compared with those of 20 μg·mL-1 5-fluorouracil (5-Fu, the control) applied to OSCC cells, when the ratio of OSCC cell numbers were measured between the treatment of different concentrations of HNK to the 5-Fu treatment for 48 h. HNK is a promising compound that can be potentially used as a novel treatment agent for human OSCC.
基金Supported by Hamburger Stiftung zur Forderung der KrebsbekampfungNo.188 to Grobe A and Riethdorf SERC Advanced Investigator Grant "DISSECT"(Pantel K),No.269081.
文摘Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.
文摘Oral squamous cell carcinoma(OSCC) is a common malignant tumor of the head and neck, and recurrence is an important prognostic factor in patients with OSCC. We explored the factors associated with recurrence of OSCC and analyzed the survival of patients after recurrence. Clinicopathologic and follow-up data of 275 patients with OSCC treated by surgery in the Cancer Institute and Hospital of Tianjin Medical University between 2002 and 2006 were analyzed. Recurrence factors were analyzed with Chisquare or Fisher′s exact test and multivariate analysis. The prognosis of patients after recurrence was analyzed with the Kaplan-Meier method and log-rank test. The recurrence rate was 32.7%. The recurrence time ranged from 2 to 96 months, with a median of 14 months. Univariate analysis showed that T stage, degree of differentiation, pN stage, flap application, resection margin, and lymphovascular invasion were factors of recurrence (P<0.05). Multivariate analysis showed that T stage, degree of differentiation, and pN stage were independent factors of recurrence (P<0.001). The differences in gender, age, tumor site, region of lymph node metastasis, and perineural invasion between the recurrence and non-recurrence groups were not significant (P>0.05). Kaplan-Meier and log-rank tests showed that the 2- and 5-year survival rates were significantly lower in the recurrence group than in non-recurrence group(67.6% vs. 88.0%, 31.8% vs. 79.9%, P<0.001). Therefore, to improve prognosis, we recommend extended local excision, flap, radical neck dissection, and adjuvant chemoradiotherapy for patients more likely to undergo recurrence.
基金the Medical University of Bialystok,Poland(projectno:3-06429F)
文摘The aim of the study was a determination of the levels of nitric oxide(NO)and its biological markers such as malonyldialdehyde(MDA)and nitrotyrosine in the serum of patients with squamous cell carcinoma(SCC)of the oral cavity and identification of the relationships between NO and those markers.These studies were performed on patients with SCC of the oral cavity before and after treatment.Griess reaction was used for the estimation of the total concentration of NO in serum.The nitrotyrosine level in serum was assessed with an enzyme-linked immunosorbent assay(ELISA)kit,and MDA level using a spectrophotometric assay.Higher concentrations of NO in blood serum were determined in patients with stage IV of the disease before treatment in comparison to the control group and patients with stages II and III of the disease.Moreover,higher concentrations of MDA and nitrotyrosine were determined in the serum of patients in all stages of the disease in comparison to healthy people.After treatment,lower concentrations of NO in the serum of patients with stage IV of the disease were observed in comparison to the amounts obtained prior to treatment.In addition,lower levels of nitrotyrosine in the serum of patients with all stages of the disease were recorded,whereas higher concentrations of MDA were determined in these patients in comparison to results obtained before treatment.The compounds formed with the contribution of NO,such as MDA and nitrotyrosine,may lead to cancer progression in patients with SCC of the oral cavity,and contribute to formation of resistance to therapy in these patients as well.Moreover,the lack of a relationship between concentrations of NO and MDA,and between NO and nitrotyrosine in serum suggests that the process of lipid peroxidation and nitration in patients with SCC does not just depend on NO.
文摘Although a few studies have shown that vascularity is increased from normal mucosa to dysplasia to carcinoma suggesting that disease progression in the oral mucosa is accompanied by angiogenesis. The role in lymph node metastasis in oral squamous cell carcinoma (OSCC) is equivocal. Role of angiogenesis in OSCC development and metastasis is evaluated in this study. This retrospective study of 50 samples consisted of 9 normal buccal mucosa, 22 leukoplakias, and 19 OSCC. Polyclonal antibodies to von-Willebrand factor were used to highlight the microvessels. Images were captured and morphometric image analysis was done for microvessel density (MVD), area, and perimeter. Highest, as well as mean values of these three parameters were compared. MVD and perimeter, but not area, are significantly different between normal mucosa and OSCC, and leukoplakia and OSCC. There were no differences between normal mucosa and leukoplakia. MVD, area, and perimeter were not significantly different between the OSCC with and without lymph node metastasis. The highest and mean values of MVD are significantly correlated. In the development of OSCC, angiogenic phenotypic change occurs in carcinomas rather than in the pre-cancerous stage, and quantification of angiogenesis in OSCC does not predict the risk of lymph node metastasis.
基金supported by the National Natural ScienceFoundation of China(No.81802710).
文摘Objective:This study aimed to examine a novel method for prognostic evaluation of patients with oral squamous cell carcinoma(OSCC)based on the expression of heterogeneous nuclear ribonucleoprotein C(HNRNPC),YTH domain-binding protein 2(YTHDF2),and methyltransferase 14(METTL14).Methods:We obtained the RNA sequence and clinical information of OSCC patients from The Cancer Genome Atlas database.An optical method was established by the least absolute shrinkage and selection operator Cox regression algorithm,which was used to calculate the risk score of every sample.In addition,all samples(n=239)were classified into high-risk(n=119)and low-risk(n=120)groups,and the overall survival(OS)time and clinical characteristics were compared between groups.Moreover,bioinformatics analysis was carried out.Gene set enrichment analysis was performed to investigate the signaling pathways of HNRNPC,YTHDF2,and METTL14.Results:The two groups showed significantly different OS time,tumor grades,tumor stages,and pathologic T stages(P<0.05).The receiver operating characteristic analysis identified that our method was effective and it was more accurate than use of age,gender,tumor grade,tumor stage,pathologic T stage,and pathologic N stage in OSCC prognostic prediction.Gene set enrichment analysis revealed that HNRNPC,YTHDF2,and METTL14 were mainly associated with ubiquitin-mediated proteolysis,cell cycle,RNA degradation,and spliceosome signaling pathways.Conclusion:The method based on the expression of HNRNPC,YTHDF2,and METTL14 can predict the prognosis of patients with OSCC independently,and its prognostic value is better than that of clinicopathological characteristic indicators.
基金supported by Jinan Science and Technology Development Plans Grant (No.201121040)
文摘Objective: To observe cyclooxygenase (COX)-2 expression in normal oral mucosa (NOM), oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC) and explore its significance in the incidence of oral cancer. Methods: The immunohistochemical method and RT-PCR method were applied to detect the expression of COX-2 and MMP-7 in 10 cases with NOM, 33 cases of with OLP and 38 cases with OSCC. Results: The expression of COX-2 mRNA in OSCC tissues (68.4%, 26/38) was significantly higher than in the OLP (24.2%, 8/33) and NOM (0.0%, 0/10) ( P<0.01). The expression of MMP-7 mRNA in OSCC tissues (65.8%, 25/38) was significantly higher than in the OLP (30.3%, 10/33) and NOM (0.0%, 0/10) ( P<0.01). The expression of MMP-7 in OLP was significantly higher than in the NOM ( P<0.05). There was no significant expression of COX-2 protein in NOM, and the positive rate was 42.4% (14/33) and 89.5% (34/38) in OLP and OSCC group, respectively. The COX-2 expression in cancer tissues was significantly higher than in NOM and OLP ( P<0.05). The MMP-7 protein expression in cancer tissues (84.2%, 32/38) was significantly higher than in NOM (10.0%, 1/10) and in OLP (42.4%, 14/33), and the positive rate in OLP was significantly higher than in NOM ( P<0.01). The COX-2 expression was associated with clinical stage ( P<0.05), the MMP-7 expression was associated with clinical stage and lymph node metastasis ( P<0.05). The expressions of COX-2 and MMP-7 mRNA were positively correlated with OSCC. Conclusions: The abnormal expressions of COX-2 and MMP-7 are closely related to the biological behavior of OSCC, the MMP-7 may be induced by COX-2, and further lead to the invasion and metastasis of OSCC.
文摘Cordycepin is an active component of parasitic fungus, Cordyceps militaris, and investigated for its pharmacologic efficacy. Increasing evidence supports the anti-tumoral effects of Cordycepin in various types of human solid tumors. We sought to determine the effects of Cordycepin on oral squamous cell carcinoma in vitro and in vivo. Two oral squamous cell carcinoma cell lines, KB and HSC3, were used in this study. Cells were treated with Cordycepin or diluent, followed by determinations of proliferation by sulforhodamine method and apoptosis by TUNEL assay in vitro. For in vivo experiments, tumor cells were transplanted into nude mice, followed by treatment with Cordycepin or control diluent. In addition, cells were examined for expression of adenosine receptor isotypes, and tested whether cordycepin-induced effects were mediated through adenosine receptors by combinatorial treatment of cordycepin and antagonists specific to each isotype of adenosine receptors. Two cell lines expressed protein of all types of adenosine receptors stronger than normal oral keratinocytes. Cordycepin showed anti-proliferating effect and apoptotic effect on both cell lines in vitro in a dose dependent manner. However, any adenosine receptors did not reverse the effect of cordycepin. In our in vivo experiments, cordycepin failed to decrease the tumor volume significantly, and failed to induce more apoptosis of tumor cells. Cordycepin has anti-proliferating effect and induces apoptosis not mediated by adenosine receptor on oral squamous cell carcinoma cells in vitro. However, in vivo results suggest that cordycepin in itself has a limited value as a novel chemotherapeutic agent for oral squamous cell carcinoma.
文摘Oral squamous cell carcinoma is a neoplasm that originates from the epithelial mucosa.It is usually more frequent between the fifth and sixth decades of life,and more than 90% of carcinomas of the oral cavity are squamous cell carcinoma.It is an invasive neoplasia with a significant recurrence rate;40% of patients present with metastases in the cervical lymph nodes at the time of diagnosis.The tumor invasion front is a characteristic of tumor growth,which can be infiltrative or noninvasive.The histopathological parameters examined include the number of mitoses,depth of the tumor,invasion pattern,degree of keratinization,and nuclear pleomorphism.For the pathologist,these parameters are routinely evaluated but are not reported to the treating physician in all cases,which we consider to be useful information when determining the therapeutic route.
基金supported by grants from the Science and Technology Planning Project of Guangdong (2009B060700037, 2009B080701009, 2011B080701014)
文摘iASPP is an inhibitory member of the apoptosis-stimulating proteins of P53(ASPP) family. iASPP is over expressed in several malignant tumors and potentially affects cancer progression. However, the expression and potential role of iASPP in oral tongue squamous cell carcinoma(OTSCC) have not been addressed. In our study, we detected iASPP expression in OTSCC by immunohistochemistry. iASPP expression is up-regulated in OTSCC tissues. Moreover, in clinical pathology specimens, we found that increased iASPP expression correlates with poor differentiation and lymph node metastasis. Using multicellular tumor spheroids(MTS) and flow cytometry, we demonstrated that iASPP down-regulation arrests OTSCC cells at the G0/G1 phase, induces OTSCC cell apoptosis and inhibits OTSCC cell proliferation. These results indicate that iASPP plays a significant role in the progression of OTSCC and may serve as a biomarker or therapeutic target for OTSCC patients.
基金Supported by grants from the National Natural Science Foundation of China(No.813711841014238)Jilin Province Science and Technology Department(NO.20160519017JH)。
文摘Objective Several studies have revealed the critical role of long non-coding RNAs(lncRNAs)as biomarkers for diagnosing oral squamous cell carcinoma(OSCC).However,the data remain inconsistent.This meta-analysis was performed to summarize the potential of lncRNAs as OSCC biomarkers.Methods We searched PubMed,Cochrane Library,Web of Science,and China National Knowledge Infrastructure databases for literature published until December 10,2020.Study quality was assessed using Quality Assessment for Studies of Diagnostic Accuracy-2,and sensitivity,specificity,and other measures regarding lncRNAs for OSCC diagnosis were pooled using bivariate meta-analysis models.Data analyses were performed using STATA 14.0.Results Overall,8 studies with 981 cases and 585 controls were included in the pooled analysis.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic odds ratio,and area under the receiver operating characteristic curve values were as follows:0.76[95%confidence interval(CI),0.65–0.84],0.90(95%CI,0.82–0.95),7.5(95%CI,4.20–13.40),0.27(95%CI,0.18–0.39),28(95%CI,13.00–58.00),0.90(95%CI,0.87–0.93),respectively.Deeks’funnel plot asymmetry test(P=0.56)indicated no potential publication bias.Conclusion Our meta-analytical evidence suggests that lncRNAs could be employed as a potential non-invasive diagnostic tool for OSCC.
文摘Squamous cell carcinoma accounts for 90% of all oral cancers. It may affect any anatomical site in the mouth, but most commonly the tongue and the floor of the mouth. It usually arises from a pre-existing potentially malignant lesion, and occasionally de novo;but in either case from within a field of precancerized epithelium. The use of tobacco and betel quid, heavy drinking of alcoholic beverages and a diet low in fresh fruits and vegetables are well known risk factors for oral squamous cell carcinoma. Important risk factors related to the carcinoma itself that are associated with a poor prognosis include large size of the tumour at the time of diagnosis, the presence of metastases in regional lymphnodes, and a deep invasive front of the tumour. Squamous cell carcinoma is managed by surgery, radiation, and chemotherapy singularly or in combination;but regardless of the treatment modality, the five-year survival rate is poor at about 50%. This can be attributed to the fact that about two-thirds of persons with oral squamous cell carcinoma already have a large lesion at the time of diagnosis.
文摘Oral squamous cell carcinoma (OSCC) has a high incidence of cervical micrometastases and sometimes metastasizes contralaterally because of the rich lymphatic intercommunications relative to submucosal plexus of oral cavity that freely communicate across the midline, and it can facilitate the spread of neoplastic cells to any area of the neck consequently. Clinical and histopathologic factors continue to provide predictive information to contralateral neck metastases (CLNM) in OSCC, which determine prophylactic and adjuvant treatments for an individual patient. This review describes the predictive value of clinical-histopathologic factors, which relate to primary tumor and cervical lymph nodes, and surgical dissection and adjuvant treatments. In addition, the indications for elective contralateral neck dissection and adjuvant radiotherapy (aRT) and strategies for follow-up are offered, which is strongly focused by clinicians to prevent later CLNM and poor prognosis subsequently.
