CDK1 and CCNA2 play important roles in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.

CCNA2 and KIF23 are molecular targets for the prognosis of adenoid cystic carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumor type derived from glands. However, relationship between CCNA2 and KIF23, and adenoid cystic carcinoma remains unclear. METHODS: GSE36820 and GSE88804 profiles for ACC were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Weighted Gene Co-expression Network Analysis (WGCNA) was conducted. Subsequently, the construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed. A gene expression heat map was generated to visually depict the expression difference of core genes between adenoid cystic carcinoma and normal samples. TargetScan was employed to identify miRNAs that regulated central DEGs. Western blotting (WB) was conducted for cell verification. RESULTS: A total of 885 DEGs were identified. GO and KEGG analyses revealed their main enrichment in responses to chemical stimuli, cell proliferation, tissue development, and regulation of cell proliferation. The GO and KEGG results indicated significant enrichment in aldosterone-regulated sodium reabsorption, the cell cycle, and the PPAR signaling pathway. Notably, core genes (CCNA2 and KIF23) were found to be highly expressed in Adenoid Cystic Carcinoma samples and expressed at low levels in normal samples. WB validated the overexpression of CCNA2 and KIF23 in the Adenoid Cystic Carcinoma group, confirming the protein-level changes associated with cell cycle, metastasis, apoptosis, and inflammatory factors in Adenoid Cystic Carcinoma groups with gene overexpression and knockout. CONCLUSIONS: CCNA2 and KIF23 exhibit high expression levels in ACC, suggesting their potential role as molecular targets for this malignancy.

SOX9 and IL1A as the Potential Gene Biomarkers of the Oral Cancer.

OBJECTIVE: Oral cancer is one of the most common malignant tumors in the head and neck. It is easy to relapse, and the prognosis is poor. However, the molecular mechanism in the development of oral cancer is still unclear. METHODS: A total of 30 normal individuals and 30 patients with head and neck cancer who underwent surgery were recruited in the Fourth Hospital of Hebei Medical University between February 2019 and November 2021. Furthermore, Human Protein Atlas (HPA) analysis, RT-qPCR, and immunofluorescence were used to verify the expression of SOX9 and IL1A. The GSE69002 dataset was downloaded from the Gene Expression Omnibus (GEO) database. GEO2R was used to identify the differentially expressed genes (DEGs). The Protein-Protein Interaction (PPI) network was constructed by using the STRING, and Cytoscape software was performed for visualization. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for enrichment analysis were made via the DAVID, Metascape, Gene Set Enrichment Analysis (GSEA), and Bin Gene Ontology (BINGO) analysis. Gene Expression Profiling Interactive Analysis (GEPIA) analysis was used to analyze the expression level of hub genes and pathological stage. The cBioPortal can be used for mutation analysis and pathway prediction of hub genes. Kaplan Meier Plotter was used for survival analysis of hub genes. RESULTS: The relative expression level of SOX9 (P=0.021, t=4.332) and IL1A (P=0.011, t= -4.213) in oral cancer was significantly higher than that in the standard group (P<0.05). The DEGs are mainly enriched in cell division, inflammation, interleukin-12 beta-subunit binding, and interleukin- 10 receptor binding. All the differentially expressed gene pathways eventually converge in cell growth and apoptosis. No relationship between the pathologic stage and the expression of hub genes. The poor overall survival of patients with the high expression of SOX9 (Hazard Ratio (HR) = 1.46, P = 0.009) and IL1A (HR = 1.49, P = 0.008). There were strong correlations between the hub genes and the head and neck neoplasms via the Comparative Toxicogenomics Database (CTD). The immunofluorescence and PCR results showed that the level of SOX9 (P<0.001, t = -23.368) in the cancer group was significantly higher than that in the normal group; The level of IL1A in the cancer group was significantly higher than that in the normal group (P<0.001, t = -11.960). CONCLUSION: SOX9 and IL1A genes are highly expressed in oral cancer and might be potential therapeutic targets for oral cancer. The poor overall survival of patients with the high expression of SOX9 and IL1A.

COL11A1 as a potential prognostic target for oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a malignant tumor occurring in the oral cavity. However, the molecular mechanism of OSCC is not clear. Bioinformatics was used to screen and identify role of collagen type X1 alpha 1 (COL11A1) on OSCC. 200 patients with OSCC were recruited. Clinical and follow-up data were recorded and COL11A1 expression levels were tested. Pearson chi-square test and Spearman correlation coefficient were used to analyze relationship between prognosis and related parameters in patients with OSCC. Univariate and multivariate Logistic regression, univariate and multivariate Cox proportional risk regression were used for further analysis, survival curve was drawn. Through bioinformatics analysis, OSCC patients with higher expression of COL11A1 have poor overall survival compare with OSCC patients with lower expression of COL11A1 (hazard ratios [HR] = 1.32, P = .047). Pearson chi-square test showed that age (P = .011), tumor grade (P = .023), COL11A1 (P < .001) was significantly correlated with prognosis of OSCC. Univariate Logistic regression analysis showed age (odds ratio [OR] = 2.102, 95% confidence intervals [95%CI]: 1.180-3.746, P = .012), tumor grade (OR = 1.919, 95%CI: 1.093-3.372, P = .023) and COL11A1 (OR = 12.775, 95%CI: 6.509-25.071, P < .001). Multivariate Logistic regression analysis showed that COL11A1 (OR = 12.066, 95%CI: 6.042-24.096, P < .001) was significantly associated with prognosis of patients with OSCC. Univariate Cox regression analysis showed that age (HR = 1.592, 95%CI: 1.150-2.205, P = .005), tumor grade (HR = 1.460, 95%CI: 1.067-1.999, P = .018) and COL11A1 (HR = 1.848, 95%CI: 1.340-2.548, P < .001) were significantly correlated with survival time of OSCC patients. Multivariate Cox regression analysis showed that tumor grade (HR = 1.466, 95%CI: 1.064-2.020, P = .019) and COL11A1 (HR = 1.645, 95%CI: 1.164-2.325, P = .005) were significantly correlated with survival time of OSCC patients. COL11A1 is significantly correlated with occurrence of OSCC. When COL11A1 is highly expressed, prognosis of patients with OSCC is worse and the survival time is shorter.

Corneodesmosin as a potential target of oral squamous cell carcinoma.

OBJECTIVE: The relationship between oral squamous cell carcinoma (OSCC) and Corneodesmosin (CDSN) remains unclear. This study aims to explore the correlation between CDSN and the prognosis and survival time of patients with OSCC. METHODS: Bioinformatics were used to identify the hub role of CDSN in the OSCC. A total of 200 patients with OSCC were recruited. Clinical and follow-up data were recorded, and the expression level of CDSN was detected. Pearson chi-square test and Spearman correlation coefficient were used to analyze the relationship between prognosis and related parameters in patients with OSCC. Univariate and multivariate Logistic regression and Cox proportional risk regression were applied for further analysis, and receiver operating characteristic curve and survival curve of subjects were plotted. RESULTS: CDSN was identified as the most significant hub gene of the OSCC by the cytoHubba. By the comparative toxicogenomics database (CTD) analysis, there was strong relationship between the CDSN and mouth neoplasms, head and neck neoplasms, squamous cell carcinoma of head and neck. The OSCC patients with low expression level of CDSN have poor overall survival compared with the high expression level of CDSN (HR = 0.75, 95% confidence interval [95%CI]: 0.57-0.98, P = .036). Spearman correlation coefficient analysis showed that CDSN expression level was significantly correlated with prognosis (ρ = -0.528, P < .001). Multivariate Logistic regression analysis showed that poor prognosis (odds ratio [OR] = 0.096, 95%CI: 0.049-0.189, P < .001) was significantly associated with low expression of CDSN. Cox regression analysis showed that the survival time of OSCC patients was shorter when CDSN expression was low (HR = 0.588, 95%CI: 0.420-0.823, P = .002). Strong predictive value of CDSN for the OSCC survival time was obtained by the biological process (BP)-neural network and support vector machine (SVM). CONCLUSION: CDSN was significantly correlated with OSCC, and the shorter the survival time of patients with OSCC was, the worse the prognosis was.

Anti-PD-1 Therapy is Beneficial for the Survival of Patients with Oral Squamous Cell Carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck. Programmed cell death protein 1 (PD-1), and programmed cell death 1 ligand 1 (PD-L1) are often overexpressed in OSCC patients, and their expression level is closely related to tumor prognosis. The objectives of this study were: 1) to evaluate the impact of anti-PD-1 treatment on the immune system and prognosis of OSCC patients and 2) to find possible associations between T-cell immunity and anti-PD-1 therapy. Methods: A total of 120 patients (divided into two equal groups: "non-anti-PD1 therapy" and "anti-PD1 therapy") with pathologically diagnosed OSCC participated in the study. Fresh peripheral blood samples (1 mL) were collected 2 days before and 20 days after the treatment. Heparin was used as an anticoagulant. Kaplan-Meier curves were plotted to compare the non-anti-PD-1 therapy and anti-PD-1 therapy groups. Results: Based on the Spearman-rho test, we found a significant correlation between anti-PD-1 treatment and survival time (P<0.001). Univariate/multivariate Cox regression analysis revealed that anti-PD-1 therapy is a significant independent risk factor of 5-year overall survival (OS) in OSCC patients (HR: 0.110, 95% CI: 0.062-0.195, P<0.001). One-way ANOVA showed that the mean levels of IFN-γ and IL-2 and numbers of CD4+ T cells were significantly increased in the anti-PD-1 therapy group compared with the non-anti PD-1 therapy group (control). The was no change in the number of CD8+ cells between the two groups. Kaplan-Meier curve results showed that the OS of patients in the anti-PD-1 therapy group was significantly longer than that in the non-anti-PD-1 therapy group. Conclusion: Anti-PD-1 therapy is beneficial to the survival and prognosis of patients with OSCC, improves T-cell immunity, and enhances tumor regression.

Effect of pembrolizumab on T lymphocyte subsets in patients with advanced oral cancer and its therapeutic effect.

BACKGROUND: The aim of this study is to investigate changes of peripheral blood lymphocyte subsets before and after treatment with pembrolizumab for advanced oral cancer and its clinical sig-nificance. METHODS: 32 patients with advanced oral cancer who received pembrolizumab treatment were selected as observation group, 30 healthy people during the same period were selected as control group. Before treatment and in cycles 1, 2, 3 and 4 after treatment, fluid cytometry was used to detect changes in levels of lymphocyte subsets in peripheral blood of patients. RESULTS: CD3+, CD4+, CD4+/CD8 + indexes of patients with advanced oral cancer before treatment were significantly lower than those in control group (P < .05), CD8 + level was significantly increased (P < .05); After 1 cycle of pembrolizumab treatment, there was no significant difference in changes of lymphocyte subsets compared with before immunotherapy; After 2 and 3 cycles of treatment, CD3+, CD4+, CD4+/CD8 + values were higher than before the treatment (P > .05), CD8 + index was slightly lower than before treatment (P < .05); After fourth cycle of treatment, CD3+, CD4+, CD4+/CD8 + values were significantly improved compared to before treatment (P < .05), CD8 + index was significantly lower than before treatment (P < .05); In treatment process of patients with stable disease (SD)/partial response (PR), the CD3+, CD4+, CD4+/CD8 + values of fourth cycles were higher than before treatment (P < .05), CD8 + index was lower than before treatment (P < .05); During treatment of progressive disease (PD) patients, changes of lymphocyte subsets in fourth cycles were not significantly different from those before treatment (P > .05). This article shows through analysis that expression of programmed cell death ligand 1 (PD-L1) and pathological types have no obvious influence on effect of immunotherapy. Multi-factor analysis shows that it is more meaningful to observe the changes of CD3+, CD4 + and CD8 + at the same time to predict effect of immunotherapy. CONCLUSION: Pembrolizumab can regulate changes of T lymphocyte subsets in patients with advanced oral cancer, improve immune status of patients, there is no obvious adverse reaction. Monitoring changes of lymphocyte subsets during treatment can predict effect of immunotherapy.

MKI67 an potential oncogene of oral squamous cell carcinoma via the high throughput technology.

Oral squamous cell carcinoma is a malignant tumor that occurs in the oral cavity, with poor prognosis and easy recurrence. However, the relationship between MKI67 and oral squamous cell carcinoma remains unclear. The oral squamous cell carcinoma datasets GSE138206, GSE146483 and GSE184616 were downloaded from the gene expression omnibus database, and the differentially expressed genes (DEGs) were screened. The protein-protein interaction network was constructed and analyzed by search tool for the retrieval of interacting genes database and Cytoscape software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used for functional enrichment analysis. GO and KEGG analyses were performed on the whole genome, as formulated by gene set enrichment analysis. comparative toxicogenomics database was used to identify the diseases most associated with the core genes. TargetScan was used to screen miRNA regulating central DEGs. A total of 1472 DEGs were identified. GO analysis showed that the differentially expressed genes were mainly enriched in the tissues of extracellular matrix, type i interferon signaling pathway, human papillomavirus infection, adhesion spot, hepatitis C and ECM-receptor interaction. Enrichment items were similar to GO and KEGG enrichment items of differentially expressed genes. 10 core genes were obtained, and their expression was different between oral squamous cell carcinoma and normal tissue samples. MKI67 is highly expressed in oral squamous cell carcinoma and may be an oncogene in oral squamous cell carcinoma.

The exploration of new biomarkers for oral cancer through the ceRNA network and immune microenvironment analysis.

The competitive endogenous RNA (ceRNA) and tumor-penetrating immune cells may be related to the prognosis of oral cancer. However, few studies have focused on the correlation between ceRNAs and immune cells. Thus, we developed a method based on a ceRNA network and tumor-infiltrating immune cells to elucidate the molecular pathways that may predict prognosis in patients with oral cancer. Download RNAseq expression data of oral cancer and control samples from the Cancer Genome Atlas (TCGA), obtain differentially expressed genes and establish a ceRNA network. The cox analysis and lasso regression analysis were used to screen key RNAs to establish a prognostic risk assessment model, and draw a 1.3.5-year forecast nomogram. Then the CIBERSORT algorithm was used to screen important tumor immune infiltrating cells associated with oral cancer. Another prognostic predictive model related to immune cells was established. Finally, co-expression analysis was applied to explore the relationship between key genes in the ceRNA network and important immune cells. Multiple external data sets are used to test the expression of key biomarkers. We constructed prognostic risk models of ceRNA and immune cells, which included 9 differentially expressed mRNAs and 2 types of immune cells. It was discovered from the co-expression analysis that a pair of important biomarkers were associated with the prognosis of oral cancer. T cells regulatory and CGNL1 (R = 0.39, P < .001) showed a significant positive correlation. External data set validation also supports this result. In this study, we found that some crucial ceRNAs (GGCT, TRPS1, CGNL1, HENMT1, LCE3A, S100A8, ZNF347, TMEM144, TMEM192) and immune cells (T cells regulatory and Eosinophils) may be related to the prognosis of oral cancer.

SPP1 and FN1 are significant gene biomarkers of tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumor types in the oral and maxillofacial region. The etiology and pathogenesis behind TSCC is complicated. In the present study, three gene expression profiles, namely GSE31056, GSE13601 and GSE78060, were downloaded from the Gene Expression Omnibus (GEO). The GEO2R online tool was utilized to identify differentially expressed genes (DEGs) between TSCC and normal tissue samples. Furthermore, a protein-protein interaction (PPI) network was constructed and hub genes were validated and analyzed. A total of 83 common DEGs were obtained in three datasets, including 48 upregulated and 35 downregulated genes. Pathway enrichment analysis indicated that DEGs were primarily enriched in cell adhesion, extracellular matrix (ECM) organization, and proteolysis. A total of 63 nodes and 218 edges were included in the PPI network. The top 11 candidate hub genes were acquired, namely plasminogen activator urokinase (PLAU), signal transducer and activator of transcription 1, C-X-C motif chemokine ligand 12, matrix metallopeptidase (MMP) 13, secreted phosphoprotein 1 (SPP1), periostin, MMP1, MMP3, fibronectin 1 (FN1), serpin family E member 1 and snail family transcriptional repressor 2. Overall, 83 DEGs and 11 hub genes were screened from TSCC and normal individuals using bioinformatics and microarray technology. These genes may be used as diagnostic and therapeutic biomarkers for TSCC. In addition, SPP1 and FNl were identified as potential biomarkers for the progression of TSCC.

Tumor microenvironment characterization in head and neck cancer identifies prognostic and immunotherapeutically relevant gene signatures.

The tumor microenvironment (TME) is of great clinical significance for predicting the therapeutic effect of tumors. Nonetheless, there was no systematic analysis of cellular interactions in the TME of head and neck cancer (HNSC). This study used gene expression data from 816 patients with HNSC to analyze the scores of 22 immune cells. On this basis, we have established a novel TMEscore-based prognostic risk model. The relationship between TMEscore and clinical and genomic characteristics was analyzed. The sample was divided into risk-H and risk-L groups based on the prognosis risk model of TMEscore, with significant differences in overall survival between the two groups (log rank p < 0.001). In terms of clinical features, the TMEscore is closely related to the T staging, Grade, and HPV. As for genomic characteristics, the genomic features of the Risk-H samples are a low expression of immune-related genes and high-frequency mutations of TP53 and CEP152. This model was validated in an external test set, in which the prognosis for Risk-H group and Risk-L group was also significantly different (log rank p = 0.017). A quantitative method of TME infiltration pattern is established, which may be a potential predictor of HNSC prognosis.

[Effect of miR-204-5p on the proliferation, migration, and invasion on tongue squamous cell carcinoma SCC25 cells by targeting bromodomain-containing protein 4].

OBJECTIVE: This study aimed to explore the target relationship between miR-204-5p and bromodomain-containing protein (BRD) 4, as well as their effects on cell proliferation, migration, and invasion in tongue squamous cell carcinoma SCC25. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-204-5p and BRD4 expression levels in tongue squamous cell carcinoma and different cell lines. TargetScan and dual luciferase reporter assay were used to confirm the target relationship between miR-204-5p and BRD4. The effects of miR-204-5p on SCC25 cell proliferation were examined by cell counting kit (CCK) 8 assay, whereas those on SCC25 cell migration and invasion were determined by Transwell assay. RT-qPCR and Western blot were used to detect the effects of miR-204-5p mimics and inhibitors on BRD4 expression. Transwell and CCK8 assays were used to detect the effects of miR-204-5p on proliferation, migration, and invasion through BRD4 regulation. RESULTS: miR-204-5p was significantly downregulated in the tissues and cells of squamous cell carcinoma, and BRD4 showed the opposite result. The increase in miR-204-5p expression can inhibit the proliferation, migration, and invasion of SCC25 cells. TargetScan and luciferase test confirmed that miR-204-5p and BRD4 had a negative regulatory relationship with BRD4, respectively. Moreover, miR-204-5p mimics can inhibit BRD4 expression, and miR-204-5p inhibitors can promote BRD4 expression upregulation. When miR-204-5p and BRD4 were overexpressed in SCC25 cells, BRD4 can make up for the inhibitory effect of miR-204-5p on SCC25 cells. CONCLUSIONS: miR-204-5p could inhibit proliferation, migration and invasion in tongue squamous cell carcinoma SCC25 cells by targeting BRD4 gene.

[Expression and clinical significance of Spindly and Bub3 in oral squamous cell carcinoma].

PURPOSE: To investigate the expression and significance of Spindly and Bub3 in oral squamous cell carcinoma(OSCC). METHODS: Sixty-five patients with OSCC admitted to the Fourth Hospital of Hebei Medical University from March 2017 to March 2019 were enrolled. RT-PCR was used to detect the expression of Spindly and Bub3 mRNA in oral squamous cell carcinoma and adjacent normal tissues from the patients. OSCC cell line was cultured. After siRNA transfection interference with the expression of Spindly and Bub3 genes, cell viability was detected by MTT assay, and the cell migration ability was detected by scratch test. Statistical analysis was performed with SPSS 22.0 software package RESULTS: The expression levels of Spindly and Bub3 mRNA in OSCC were significantly higher in adjacent tissues(P<0.05). The expression of Spindly and Bub3 mRNA was related to TNM staging, clinical staging and lymph node metastasis (P<0.05). The 5-year survival rate of patients with high expression of Spindly, Bub3, Spindly/Bub3 were significantly higher than the counterparts with low expression, and the 5-year survival rate of patients with high expression of Spindly/Bub3 was significantly lower than that of patients with high expression of Spindly and Bub3(P<0.05). The expression level of Spindly in siRNA-Spindly group was significantly lower than that in Spindly negative control group and blank control group, and the expression level of Bub3 in siRNA-Bub3 group was also significantly lower than that in Bub3 negative control group and blank control group. The expression level of Spindly in siRNA-Spindly group was significantly lower than that in Spindly negative control group and blank control group, and the expression level of Bub3 in siRNA-Bub3 group was also lower than that in Bub3 negative control group and blank control group. The migration ability of cells in siRNA-Spindly group at 24 and 48 hours was significantly lower than that in Spindly negative control group and blank control group; the migration ability at 24 and 48 hours was significantly lower than that of Bub3 negative control group and blank control group(P<0.05). CONCLUSIONS: Spindly and Bub3 are highly expressed in OSCC. Specific inhibition of Spindly and Bub3 gene expression can reduce the proliferation and migration of cancer cells, which might be used as one of the targets for the treatment of OSCC.

Identification of Key Biomarkers and Potential Molecular Mechanisms in Oral Squamous Cell Carcinoma by Bioinformatics Analysis.

The aim of this study was to explore the key genes, microRNA (miRNA), and the pathogenesis of oral squamous cell carcinoma (OSCC) at the molecular level through the analysis of bioinformatics, which could provide a theoretical basis for the screening of drug targets. Data of OSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified via GEO2R analysis. Next, protein-protein interaction (PPI) network of DEGs was constructed through Search Tool for the Retrieval of Interacting Gene and visualized via Cytoscape, whereas the hub genes were screened out with Cytoscape. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by Database for Annotation, Visualization and Integrated Discovery. The miRNA, which might regulate hub genes, were screened out with TargetScan and GO and KEGG analysis of miRNA was performed by DNA Intelligent Analysis-miRPath. Survival analyses of DEGs were conducted via the Kaplan-Meier plotter. Finally, the relationships between gene products and tumors were analyzed by Comparative Toxicogenomics Database. A total of 121 differential genes were identified. One hundred thirty-five GO terms and 56 pathways were obtained, which were mainly related to PI3K-Akt signals pathway, FoxO signaling pathway, Wnt signaling pathway, cell cycle, p53 signaling pathway, cellular senescence, and other pathways; 10 genes were identified as hub genes through modules analyses in the PPI network. Finally, a survival analysis of 10 hub genes was conducted, which showed that the low expression of matrix metalloproteinase (MMP)1, MMP3, and C-X-C motif chemokine ligand (CXCL)1 and the high expression of CXCL9 and CXCL10 resulted in a significantly poor 5-year overall survival rate in patients with OSCC. In this study, the DEGs of OSCC was analyzed, which assists us in a systematic understanding of the pathogenicity underlying occurrence and development of OSCC. The MMP1, MMP3, CXCL1, CXCL9, and CXCL10 genes might be used as potential targets to improve diagnosis and as immunotherapy biomarkers for OSCC.

Using weighted gene co-expression network analysis to identify key modules and hub genes in tongue squamous cell carcinoma.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors in head and neck, but its molecular mechanism is not clear. METHODS: Weighted gene co-expression network analysis (WGCNA) combining with gene differential expression analysis, survival analysis to screen key modules and hub genes related to the progress of TSCC. Gene Set Enrichment Analysis (GSEA) was used to identify biological pathways that might be involved. RESULTS: Weighted gene co-expression network was constructed based on dataset GSE34105. The blue module and turquoise module most related to the progress of TSCC were identified by the network. Gene Ontology (GO) enrichment analysis showed that 2 key modules were significantly enriched in apoptosis and immunity related biological processes and pathway. Network topology analysis, gene difference analysis and survival analysis were used to screen 9 hub genes (NOC2L, AIMP2, ANXA2, DIABLO, H2AFZ, MANBAL, PRDX6, SNX14, TIMM23). The expression of hub genes was significantly correlated with the prognosis of TSCC. GSEA showed that the high expression group of hub genes was mainly enriched in olfactory transduction, neuroactive ligand receptor interaction, nicotinate and nicotinamide metabolism, and the low expression group was mainly enriched in base excision repair, cysteine and methionine metabolism, oxidative phosphorylation. CONCLUSION: Two key modules and 9 hub genes screened by WGCNA were closely related to the occurrence and prognosis of TSCC. Hub genes can be used as biomarkers and potential therapeutic targets for the accurate diagnosis and treatment of TSCC in the future.

Variation and significance of secretory immunoglobulin A, interleukin 6 and dendritic cells in oral cancer.

The present study aimed to determine changes in the concentration of secretory immunoglobulin A (SIgA) and interleukin 6 (IL-6) in the saliva of patients with oral cancer, to evaluate the abnormal expression of cluster of differentiation (CD) 1a, CD83, CD80 and CD86 on dendritic cells (DCs) of oral cancer tissues and to discuss the interaction between SIgA, IL-6 and DCs in oral cancer. A total of 40 patients between 27 and 70 years of age, median age 52 years, with primary oral cancer were enrolled in the present study, and a group of 20 healthy male and female volunteers was used as the control group. The concentration of SIgA and IL-6 in the saliva of the preoperative patients was determined by ELISA. The expression levels of CD1a, CD83, CD80 and CD86 were detected by immunohistochemistry and flow cytometry, which was performed on histopathological sections from paraffin-embedded tumor and corresponding adjacent control tissues. The specimens were assessed using the semi-quantitative immunoreactive score (IRS). The concentration of SIgA in the saliva from patients with oral cancer decreased, whereas the IL-6 level significantly increased compared with the control subjects (P<0.05). In addition, the decrease of SIgA level and increase of IL-6 level exhibited a negative correlation (r=-0.543, P<0.05). According to the IRS score, the expression levels of CD1a, CD83, CD80 and CD86 in the cancer tissue were lower than the expression levels of the control group (P<0.05). Furthermore, the expression of CD80 and CD86 exhibited no correlation with histological grade or pathological type (P>0.05), but exhibited a negative correlation with clinical stage and lymph node metastasis (P<0.05). The concentration of SIgA and IL-6 in saliva may be used as an auxiliary diagnostic indicator for oral cancer. The detection of CD80 and CD86 expressed on DCs in oral cancer tissue may be useful for the diagnosis and evaluation of the prognosis of tumors. The present study hypothesized that the use of SIgA vaccines or IL-6 inhibitors may be useful for reversing the immune deficiency associated with DCs in oral cancer.

Tetrandrine attenuates spatial memory impairment and hippocampal neuroinflammation via inhibiting NF-κB activation in a rat model of Alzheimer's disease induced by amyloid-ß(1-42).

BACKGROUND: The neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb radix Stephania tetrandra, has been demonstrated to decrease the expression of proinflammatory mediators by inhibition of nuclear factor-κB (NF-κB) activation. The purpose of the study was to investigate effects of tetrandrine on experimental model of AD. MATERIALS AND METHODS: Tetrandrine was administered in a rat model of AD induced by amyloid-ß (Aß)(1-42). The learning and memory impairment was examined using Morris water maze; the extent of histological injury in hippocampus was determined by Nissl staining; NF-κB DNA binding activity was assessed by electrophoretic mobility shift assay; the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß was measured by enzyme-linked immunosorbent assay. RESULTS: A significant improvement was observed in learning and memory impairment in rats with tetrandrine, and the increase in NF-κB DNA binding activity, the over-expression in IL-1ß and TNF-α as well as the increased histological injury in hippocampus in rats induced by Aß(1-42) were significantly reduced following administration of tetrandrine. CONCLUSION: Tetrandrine could significantly ameliorate Aß(1-42)-induced spatial learning and memory impairment, and the beneficial effect of tetrandrine treatment could be linked, at least in part, to the inhibition of NF-κB activity and the downregulation of expression of IL-1ß and TNF-α, suggesting that administration of tetrandrine may provide a therapeutic approach for AD.