FSD1蛋白对胶质瘤干细胞侵袭的影响

The effect of FSD1 protein on the invasion of glioma stem cells

目的研究具有SPRY结构域的纤连蛋白Ⅲ型(FSD1)在胶质瘤干细胞侵袭中发挥的作用,探索新的胶质瘤肿瘤标志物或治疗靶点。方法利用TCGA数据库数据,分析比较在多形性成胶质细胞瘤(GBM)组织、正常脑组织及不同分型级别胶质瘤组织中的FSD1的mRNA表达水平,并分析FSD1 mRNA表达水平与胶质瘤患者预后的相关性。利用慢病毒感染体系,在胶质瘤干细胞(GSC)T4121和D456中稳定过表达FSD1蛋白,通过Transwell侵袭实验检测过表达FSD1蛋白对T4121和D456两种GSC侵袭能力的影响。结果 FSD1基因在GBM组织中mRNA表达水平显著低于正常脑组织(P<0.01);FSD1的mRNA表达水平随胶质瘤分型级别提高而降低(Ⅱ级与Ⅲ级比较,P<0.05,Ⅲ级与Ⅳ级比较,P<0.01);FSD1 mRNA低表达的胶质瘤患者的生存期显著低于高表达患者(P<0.01)。在T4121和D456两种GSC细胞系中,过表达FSD1蛋白的GSC侵袭细胞数显著低于空白对照组(2株细胞系中均为P<0.01)。结论 FSD1表达水平是胶质瘤恶性程度的一个临床相关因素,低水平FSD1有利于维持GSC的侵袭能力。

Objective To investigate the effect of fibronectin type Ⅲ and SPRY domain containing 1(FSD1)protein on the invasion of glioma stem cells(GSCs),so as to probe into the new biomarkers or potential therapeutic targets for gliomas. Methods The Cancer Genome Altas(TCGA)database data were used to analyze and compare the FSD1 gene expression(the FSD1 mRNA level)in the glioblatoma(also known as glioblastoma multiforme,GBM)and normal brain tissues as well as in the different grade glioma tissues,and the correlation of the FDS1 gene expression(mRNA level)with the survival prognosis of patients was also analyzed using the TCGA database data. The lentivirus was used to overexpress the FSD1 protein in the GSCs,T4121 and D456. The effect of the overexpressed FSD1 protein on the invasive ability of the GSCs,T4121 and D456 was evaluated by Transwell invasion assay. Results The FSD1 gene expression(mRNA level)was significantly lower in GBM than in normal brain(P<0.01). The FSD1 gene expression(the mRNA level)in gliomas significantly decreased with the increase of the gliomas grade(gradeⅡvs Ⅲ,P<0.05;gradeⅢvs Ⅳ,P<0.01). The survival prognosis of patients with gilomas was well associated with the level of FSD1 gene expression(the FSD1 mRNA level),as indicated by the overall survival rate of the patients,which was significantly lower in the patients with the low FSD1 mRNA level than in the patients with the high FSD1 mRNA level(P<0.01). In the Transwell invasion assay,the count of the invasive cell numbers significantly decreased in the FSD1 protein-overexpressed T421 and D456 groups than in the corresponding control group(P<0.01 in both T4121 and D456 cell lines). Conclusion There is a clinical relevance of the FSD1 expression for the malignant progression of gliomas(the grade of gliomas). The low level FSD1 is favorable for keeping the invasive ability in GSCs.