Mechanism Of SHCBP1 Overexpression On Migration And Invasion Of Gliomas And Its Clinical Application

BackgroundGlioma is a tumor that originates in glial cells and occurs in the neuroectodermal layer.It is also the most common primary malignant tumor in the central nervous system,accounting for about 30% of all brain and central nervous system tumors and accounting for all malignant brains.80% of tumors have a cumulative 1-year survival rate of less than 30%.In spite of the surgical resection,conventional temozolomide(TMZ)chemotherapy and radiotherapy in all aspects,but the prognosis of patients with malignant glioma is still poor,most of the patients with glioma eventually died of the disease.Therefore,further study the molecular mechanism of glioma development,deepen the understanding of the degradation process of glioma,the clinical diagnosis of glioma and molecular targeted therapy provides valuable theory reference.Glioma is one of the most common and aggressive tumors in brain central nervous tumors,and is one of the worst prognosis in all malignant tumors.The median survival time of high-grade glioma is about 12 to 14 months,and most patients with high grade glioma die within 2 years afterdiagnosis.Therefore,it is very important to identify the genes for proliferation,migration and invasion of glioma cells.Secondly,it can be used as a molecular marker for the early clinical diagnosis and prognosis of gliomas,providing a reference for the early diagnosis of the disease,the development of clinical treatment plans,and postoperative care and nursing rehabilitation programs.PurposeTo investigate the relationship between SHCBP1 expression and prognosis in glioma and the mechanism of SHCBP1 in glioma and to explore the possibility of SHCBP1 as a diagnostic and prognostic evaluation biomarker for gliomas.It is expected to provide a valuable theoretical reference for the early disease diagnosis,clinical treatment,and the formulation and implementation of prognostic nursing plans for gliomas.MethodSubjects: From January 2007 to December 2013,86 patients with glioma surgeries were from a tertiary level hospital in Yuexiu District,Guangdong Province.The clinical and pathological data and follow-up data were all complete histopathological specimens were well preserved and the postoperative treatment and survival of patients were followed up(follow-up until December 2017).Experimental methods: The expression of SHCBP1 protein in IHC tissue was detected by histopathological specimens from patients.The expression of SHCBP1 in glioma tissues and normal brain tissues was detected by qRT-PCR.Patients were followed up for survival time and survival rate.SPSS 23.0 statistical software was used to analyze the correlation between SHCBP1 protein expression and prognosis in glioma tissues.The roles and relationships of SHCBP1 and its related signaling pathways were examined by Western Blot,cell scratch assay,Transwell cell invasion and invasion assay,3D sphere invasion assay and Luciferase assay.Research content:1.To investigate SHCBP1 gene expression in clinical glioma tissue samples;2.To study the biological function of SHCBP1 gene and its effect on cell proliferation,metastasis and invasion by over-expression and siRNA-mediated knockdown;3.To examine the correlation between SHCBP1 overexpression and activation / inhibition of related signaling pathways and its molecular mechanisms;4.Through the follow-up of relevant cases and the analysis of the impact of prognosis,with a view to provide new theoretical ideas and references for clinical treatment of glioma,nursing interventions and postoperative rehabilitation guidance,etc.,with more important clinical practical value.Result1.Analysis of clinical specimens of patients with gliomas,SHCBP1 expression was up-regulated in gliomas and was significantly associated with the clinical stage and poor prognosis of gliomas(P <0.01).Moreover,the expression of SHCBP1 in glioma tissue was significantly higher than that in normal brain tissue.After comparison and analysis of the data,the difference was statistically significant(P<0.05);2.After in vitro experiments demonstrated that overexpression of SHCBP1 promoted glioma cell migration and invasion,silencing SHCBP1 significantly inhibited glioma cell migration and invasion;3.The up-regulation of SHCBP1 activates the NF-κB signaling pathway in glioma cells,which promotes the proliferation and migration of gliomas;and the silencing of SHCBP1 leads to the inhibition of the expression of target genes downstream of the NF-κB signaling pathway,which further inhibits the glioma progression;4.Through case data collecting and follow-up and data record analysis,SHCBP1 expression significantly influences postoperative survival and recurrence time in patients with glioma,who with higher SHCBP1 gene expression had earlier relapses and shorter survival times.Conclusion1.Members of the SHCBP1,Src homologues and the Shc family of collagens are significantly overexpressed in glioma tissue and glioma cell lines compared to corresponding normal tissues and cells;2.Ectopicoverexpression of SHCBP1 promoted glioma cell migration and invasion,whereas knockdown of endogenous SHCBP1 had the opposite effect;3.SHCBP1 promotes the glioma invasiveness by activating the NF-κB signaling pathway;4.The determination of biological indicators for the early diagnosis and prognosis evaluation of gliomas can enable clinical health nursing workers to play a guiding role in preoperative,postoperative treatment and nursing rehabilitation of glioma patients.