中文摘要：

目的：检测肿瘤相关成纤维细胞Twist1基因表达,探讨肿瘤相关成纤维细胞高表达Twist1对卵巢癌侵袭能力的影响。方法：CSIOVDB数据库检索Twist1基因在卵巢各种组织类型中的表达水平。分离原代正常成纤维细胞（NOF）,以及卵巢癌患者的原代肿瘤相关成纤维细胞（CAF）,免疫荧光实验验证Twist1基因在NOF和卵巢癌CAF细胞中的表达差异。TCGA数据库489例卵巢癌中从mRNA水平验证Twist1与CAF经典活化指标FAP的相关性,以及炎症因子IL-6的相关性。GSEA（Gene Set Enrichment Analysis）软件探究CAF高表达Twist1与IL-6通路富集的关系。Western blot法验证下调Twist1基因对IL-6表达的影响。Transwell实验探究卵巢癌CAF-肿瘤细胞共培养体系中IL-6对卵巢癌细胞系SKOV3侵袭能力的影响。结果：Twist1基因在卵巢癌CAF中的表达水平明显高于肿瘤细胞和正常成纤维细胞。TCGA数据库中Twist1基因和FAP及IL-6基因呈显著正相关（P〈0.0001）。GSEA软件分析结果示,卵巢癌患者中CAF高表达Twist1的同时,肿瘤上皮表现为IL-6通路明显富集（P〈0.05,FDR〈25%）。Western blot法结果表明,Twist1基因下调后,IL-6基因表达量明显降低。在共培养体系中加IL-6中和抗体,卵巢癌细胞侵袭力明显下降。结论：肿瘤相关成纤维细胞高表达Twist1,可能通过提高IL-6水平增强卵巢癌侵袭能力。

英文摘要：

Objective：To explore the influence of Twist1 overexpression in ovarian cancer associated fibroblast（CAF） on ovarian cancer invasion.Methods：Twist1 gene was retrieved in CSIOVDB online Database to identify expression in different tissue types.After isolation of primary normal ovarian fibroblast and primary cancer associated fibroblast,immunofluorescence was performed to detect Twist1 expression in cell level.TCGA database was used to analyze the mRNA expressions correlation between Twist1 and CAF marker FAP as well as IL-6 among 489 ovarian cancers.Gene Set Enrichment Analysis（GSEA） software was performed to explore the relationship between Twist1 overexpression CAF and IL-6 pathway in ovarian cancer.The influence of Twist1 silence on IL-6 expression was confirmed by Western blot.Transwell was employed to explore the invasion of SKOV3 after IL-6 blocked.Result：Twist1 expression level in ovarian cancer associated fibroblast was apparently higher than normal ovary fibroblast and normal ovary epithelium.The mRNA levels of Twist1 display significantly positivelycorrelated to CAF marker FAP and IL-6 mRNA expression level in TCGA datasets（P〈0.0001）.Gene Set Enrichment Analysis（GSEA） software analytical results demonstrated that Twist1 overexpression in CAF was related to IL-6 pathway enrichment（P〈0.05,FDR25%）.After silencing Twist1 of CAF,IL-6 expression levels also decreased.IL-6 was blocked by antibody in CAF-Ovarian cancer coculture system,invasion of ovarian cancer cells significantly decreased.Conclusion：Twist1 overexpression in CAF can promote invasion of ovarian cancer cells probably through IL-6 secretion.