RESUMEN
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration.
RESUMEN
@# Objective: To explore the role of Thy-1 cell surface antigen（Thy-1）in promoting epithelial-mesenchymal transition (EMT) in liver cancer HepG2 and MHCC-97 cells by regulating Notch1 pathway. Methods: MHCC-97 cells with high metastatic characteristics and HepG2 cells with low metastatic characteristics were selected as subjects. WB was used to detect the expression levels of Thy-1 and Notch1 in cells. MHCC-97 and HepG2 cells were transfected with lentivirus to construct cells with high and low expression of Thy-1 protein. Cells were treated with Notch1 agonist rhNF-κB (1 gsu/ml) and Notch1 inhibitor MW167 (100 μmol/L) for 24 h respectively. Transwell assay was used to detect the effect of Thy-1 expression on cell invasion; qPCR was used to detect the effect on Notch1 mRNA expression; WB was used to detect the effect on intracellular EMT-related protein expression. Results: The expression levels of Thy-1 and Notch1 in MHCC-97 cells were higher than those in HepG2 cells (P<0.05). Thy-1 overexpressing HepG2 cells and Thy-1 low expressing MHCC-97 cells were successfully constructed. Compared with HepG2 cells, the invasion ability of Thy-1 overexpressing HepG2 cells was significantly enhanced (183.23±55.34 vs 475.78±80.37, P<0.05), vimentin expression was significantly increased (P<0.05), epithelial cadherin protein expression was significantly decreased (P<0.05), and the expression level of Notch1 mRNAwas significantly increased (P<0.05). Compared with MHCC-97 cells, the invasion ability of Thy-1 silenced MHCC97 cells was significantly decreased (543.56±77.94 vs 237.44±62.18, P<0.05), the expression of vimentin was significantly decreased (P<0.05), epithelial cadherin protein expression was significantly increased (P<0.05), and Notch1 mRNA expression level was significantly decreased (P<0.05). Treatment of liver cancer cells with Notch1 activators or inhibitors can reverse the changes caused by Thy-1 silencing or overexpression. Conclusion: Thy-1 can affect the EMT process of HepG2 and MHCC-97 cells by regulating the expression of Notch1.