The role of long non-coding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) in sinonasal squamous cell carcinoma (SNSCC) remained obscure. Target genes and potential binding sites of NEAT1, miR-195-5p and VEGFA were predicted using Starbase and TargetScan, and confirmed by dual-luciferase reporter assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of NEAT1, vascular endothelial growth factor A (VEGFA) and miR-195-5p. Pearson’s correlation analysis of NEAT1, miR-195-5p and VEGFA was conducted. Cell viability, apoptosis and tube formation capability were assessed by MTT assay, flow cytometry and capillary-like tube formation assay, respectively. Expressions of VEGFA and proteins related to the phosphatidylinositide 3-kinases/Protein Kinase B (PI3K/AKT) pathway were measured by Western blot. In SNSCC tissues and cells, the expressions of NEAT1 and VEGFA were up-regulated while the expression of miR-195-5p was down-regulated, and NEAT1 was negatively correlated with miR-195-5p yet positively correlated with VEGFA. Overexpressed VEGFA promoted the viability and capillary-like tube formation of SNSCC cells yet suppressed their apoptosis, while silencing VEGFA led to the opposite results. MiR-195-5p could bind to NEAT1, and down-regulating miR-195-5p reversed the effects of silencing NEAT1 on the expressions of NEAT1 and miR-195-5p, cell viability, apoptosis and capillary-like tube formation as well as PI3K/AKT pathway activation. VEGFA was the target of miR-195-5p, and overexpressed VEGFA reversed the effects of miR-195-5p. Down-regulating NEAT1 inhibited the viability and vasculogenic mimicry formation of SNSCC cells yet promoted their apoptosis via the miR-195-5p/VEGFA axis, providing a possible therapeutic target for SNSCC treatment.
Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most serious diseases affecting populations worldwide and lymph node metastasis is a key pathological feature of HNSCC which predicts poor survival. However, the molecular mechanisms associated with the development of lymph node metastasis in HNSCC have not been fully elucidated.Methods: Differentially expressed genes (DEGs) were identified in two HNSCC datasets (GES6631 and GES58911). Functional annotation analysis was constructed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Meanwhile, the proteinprotein interaction (PPI) network and module analysis using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape were carried out to identify the hub genes. The expression differences, overall survival (OS), and disease-free survival (DFS) of hub genes were analyzed by Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and verified by immunohistochemistry (IHC) from Human Protein Atlas (HPA). Moreover, receiver operating characteristic (ROC) curve analysis was conducted to judge whether those hub genes had good diagnostic and prognostic ability, and the web tool Tumor Immune Estimation Resource (TIMER) was used to analyze the correlation of hub genes' expression and immune infiltration.Results: In total, 913 DEGs including 476 upregulated and 437 downregulated genes were identified.The genes Aurora kinase A (AURKA), CyclinB1 (CCNB1), Cyclin-dependent kinase regulatory subunit 1B (CKS1B), Serpin Family H Member 1(SERPINH1), and Transforming growth factor-beta-induced protein (TGFBI) were screened out as hub genes and were associated with lymph node metastasis, showing notably abnormal expression in HNSCC samples, and the high expression of all the hub genes in HNSCC patients was related to worse overall survival. Conclusions:The genes AURKA, CCNB1, CKS1B, SERPINH1, and TGFBI may be involved in the lymph node metastasis of HNSCC and reveal the potential to serve as molecular biomarkers in the diagnosis of HNSCC. This study may help to elucidate the molecular mechanisms of the development of lymph node metastasis and facilitate the selection of targets for the treatment and diagnosis of HNSCC.
Background: Oropharyngeal cancer (OPC) is a type of head and neck squamous cell cancer, the incidence of which has increased in recent years. Many studies have reported a variety of prognostic markers of OPC, but they are either expensive or difficult to obtain. Therefore, we retrospectively studied the prognostic value of circulating neutrophil count (CNC) in patients with OPC, with the aim of providing a theoretical basis for further prognostic stratification. Methods:The clinicopathological data of 153 patients diagnosed with OPC from January 2010 to June 2017 were retrospectively analyzed. The CNC of each patient was measured before treatment. Then, the relationship between CNC and the clinicopathological characteristics of the patients was analyzed.The receiver operating characteristic (ROC) curve was used to calculate the cutoff value of CNC. The cox proportional hazards model was used to perform univariate and multivariate analysis of the relevant prognostic factors to determine the factors related to overall survival (OS) and progression-free survival (PFS). Results:The cutoff value for CNC was 4.48. Neutrophilia was significantly associated with disease stage, P16 status, and the type of therapy. In the univariate and multivariate analyses, CNC was found to be correlated with OS and PFS. Increased neutrophil count was predictive of poor OS (P<0.001) and PFS (P=0.001). Neutrophil count was an independent risk factor for OS (HR =2.09, 95% CI: 1.25-3.51, P=0.005) and PFS (HR =1.78, 95% CI: 1.10-2.88, P=0.02) in patients with OPC.Conclusions: Pre-treatment CNC is an independent prognostic factor for OPC.
Background: Oropharyngeal squamous cell carcinoma (OPSCC) is a kind of squamous cell carcinoma of head and neck, and its incidence is on the rise in recent years. A variety of prognostic markers for OPSCC have been reported in many studies, but they are expensive or difficult to obtain. So, we retrospectively studied the prognostic significance of cytokeratin 19 soluble fragment (Cyfra21-1) in patients with OPSCC, in order to provide theoretical basis for accurate prognosis assessment. Methods: A retrospective analysis of the clinicopathological data of 85 OPSCC patients with concurrent radiotherapy and chemotherapy (CRT) admitted from January 2010 to June 2017. Serum Cyfra21-1 levels were measured before treatment. Analyze the relationship between Cyfra21-1 and clinical pathological characteristics of patients. The receiver operating characteristic (ROC) curve was used to calculate the cutoff value of Cyfra21-1. The Cox proportional hazard model was used to conduct univariate and multivariate analysis of related prognostic factors, and to determine the factors related to overall survival (OS) and progression-free survival (PFS).Results: The cutoff value for Cyfra21-1 was 2.93 ng/mL. The baseline data of patients in different Cyfra21-1 groups were balanced and comparable. In the univariate and multivariate analyses, it was found that Cyfra21-1 was associated with OS and PFS. A measurement of Cyfra21-1 ≥2.93 ng/mL indicated poor OS (P<0.001) and PFS (P=0.001). After adjusting for age and disease stage, Cyfra21-1 can independently affect the OS (HR =3.57, 95% CI: 1.60-7.99, P=0.002) and PFS (HR =2.89, 95% CI: 1.41-5.91, P=0.004) of patients with OPSCC treated with CRT.Conclusions: Pre-treatment Cyfra21-1 can be used as a prognostic marker for patients with OPSCC treated with CRT, which has important clinical significance.
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