基于生物信息学分析丝甘蛋白聚糖对卵巢癌耐药性的影响及作用机制
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篇名: 基于生物信息学分析丝甘蛋白聚糖对卵巢癌耐药性的影响及作用机制
TITLE:
摘要: 目的:研究丝甘蛋白聚糖(SRGN)对卵巢癌耐药性的影响及作用机制。方法:采用基因表达谱交互分析工具(GEPIA)提取卵巢癌相关数据集并分析SRGN mRNA在人类正常卵巢组织与卵巢癌组织的表达差异;基于基因表达数据库(GEO)获取SRGN mRNA在顺铂敏感性与顺铂耐药性卵巢癌细胞株(A2780)中的表达差异;采用STRING在线数据库筛选SRGN的互作蛋白(置信度为0.900,联结数为10),然后通过生物学信息注释数据库(DAVID)进行京都基因和基因组百科全书(KEGG)代谢通路分析,预测SRGN调节卵巢癌耐药性的潜在通路;采用医学本体信息检索平台COREMINE挖掘SRGN、卵巢癌、耐药性三者显著关联的生物过程。结果:SRGN mRNA在卵巢癌组织中的表达显著高于正常卵巢组织(P<0.05),在顺铂耐药性卵巢癌细胞株中表达显著高于顺铂敏感性卵巢癌细胞株(P<0.001)。筛选出10个与SRGN互作的蛋白,包括白蛋白、转化生长因子β1、血小板因子4、血纤维蛋白溶酶原、血管内皮生长因子A等;SRGN参与调节卵巢癌耐药性的KEGG代谢通路有缺氧诱导因子1α信号通路、细胞因子-细胞因子受体通路、凝血与补体级联反应信号通路等,生物过程有基因表达、细胞生长、凋亡过程、细胞死亡。结论:SRGN介导卵巢癌耐药可能与缺氧诱导因子1α信号通路、细胞因子-细胞因子受体通路等有关。
ABSTRACT: OBJECTIVE: To study the effects of serglycan (SRGN) on drug resistance of ovarian cancer and its mechanism. METHODS: Gene expression profile interactive analysis tool (GEPIA) was used to extract related data set of ovarian cancer and analyze the difference of mRNA expression of SRGN between normal ovary tissue and ovarian cancer tissue. Gene expression database (GEO) was adopted to obtain the difference of the mRNA expression of SRGN in cisplatin sensitive and cisplatin resistant cell lines (A2780). STRING online database was used to screen proteins interacting with SRGN (confidence degree: 0.900, interactors: 10). Adopted biological information annotation database (DAVID) to analysis Kyoto encyclopedia of genes and genomers(KEGG)metabolism pathway to predict the potential pathways of SRGN regulating drug resistance of ovarian cancer. Medical ontology information retrieval platform COREMINE was used to mine the biological processes of significant relationship of SRGN and ovarian cancer with drug resistance. RESULTS: mRNA expression of SRGN in ovarian cancer tissue was significantly higher than normal ovarian tissue (P<0.05). mRNA expression of SRGN in cisplatin resistant ovarian cancer was significantly higher than cisplatin sensitive ovarian cancer (P<0.001). 10 proteins interacting with SRGN were screened, including albumin, transforming growth factor β1, platelet factor 4, fibrinolysin and vascular endothelial growth factor A. SRGN participated in KEGG metabolism pathway of regulating drug resistance of ovarian cancer, including HIF1α pathway, cytokine-cytokine receptor pathway, coagulation and complement cascades pathway, etc. Biological processes included gene expression, cell growth, apoptosis and cell death. CONCLUSION: SRGN mediates drug resistance of ovarian cancer, which is associated with HIF1α signaling pathway and cytokine-cytokine receptor pathway.
期刊: 2019年第30卷第1期
作者: 许丁文,熊彦,严慧深,雒森,姚伟娟
AUTHORS: XU Dingwen,XIONG Yan,YAN Huishen,LUO Sen,YAO Weijuan
关键字: 丝甘蛋白聚糖;卵巢癌;耐药性;KEGG代谢通路;生物信息学
KEYWORDS: Serglycan; Ovarian cancer; Drug resistance; KEGG metabolism pathway; Bioinformatics
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