基于生物信息学分析高表达EFNA1对卵巢癌铂类耐药的影响Bioinformatics-based analysis of the effect of high expression of EFNA1 on platinum drug resistance in ovarian cancer
王可可,冉晓敏,严慧深,阎可,何亮
WANG Keke,RAN Xiaomin,YAN Huishen,YAN Ke,HE Liang
摘要(Abstract):
目的 研究肝配蛋白A1(ephrin-A1,EFNA1)与卵巢癌铂类耐药的关系。方法 运用Oncomine和基因表达谱交互分析在线工具分析EFNA1在全身肿瘤组织和卵巢癌组织中的表达;TISIDB结合TNMplot以及muTarget分析EFNA1与不同卵巢癌病理参数的相关性;Kaplan-Meier Plotter结合PrognoScan进行EFNA1表达量与卵巢癌患者生存率相关性分析;GEO数据库分析EFNA1在铂类敏感性与铂类耐药性的卵巢癌细胞株中的表达差异;采用反转录-聚合酶链反应及Western blot检测EFNA1在顺铂敏感或耐药性卵巢癌细胞系中的表达,CCK8检测顺铂耐药性卵巢癌细胞系A2780-DDP增殖,流式细胞术检测A2780-DDP细胞凋亡,Coremine文本挖掘分析EFNA1介导卵巢癌顺铂耐药的生物过程。结果 EFNA1在卵巢癌中高表达,而且与卵巢癌患者的病理参数、生存率显著相关;EFNA1在铂类耐药性卵巢癌组织或细胞中高表达,并且与卵巢癌铂类化疗患者的不良预后显著相关。EFNA1敲低后抑制了顺铂处理后的A2780-DDP细胞的增殖,促进了凋亡。细胞增殖、凋亡、细胞周期等生物过程与EFNA1介导的卵巢癌铂类耐药性显著相关。结论 高表达EFNA1与卵巢癌铂类药物化疗耐药相关。
Objective To analyze the association of EFNA1 and platinum resistance in ovarian.Methods Oncomine combined with GEPIA were used to detect the expression of EFNA1 in pan-cancer and ovarian cancer.TISIDB,TNMplot and muTarge was used to analyze correlation between EFNA1 mRNA expression level and clinicopathological parameters in ovarian cancer.Kaplan-Meier Plotter and PrognoScan were used to analyze correlation between EFNA1 mRNA expression level and survival rates in patients with ovarian cancer.GEO database was used to analyze EFNA1 expression in platinum resistant ovarian cancer tissue or cell lines.RT-PCR and Western Blot were used to detect EFNA1 expression in cisplatin sensitive or resistant ovarian cancer cell lines, CCK-8 assay were performed to evaluate the viability of A2780-DDP cells, and cell apoptosis of A2780-DDP was measured by flow cytometry.Text mining was perform by COREMINE to analyze the biological processes of EFNA1 mediated drug resistance in ovarian cancer.Results EFNA1 was upregulated in ovarian cancer, and significantly associated with clinicopathological parameters and survival rates in ovarian cancer.EFNA1 was upregulated in ovarian cancer tissue or cell lines with platinum resistance, and significantly associated with poor outcomes in ovarian cancer patients with platinum treatment.Knockdown of EFNA1 suppressed proliferation and promoted apoptosis in A2780-DDP cell treated with cisplatin.Cell proliferation, apoptotic process, and cell cycle were significantly associated with EFNA1 mediated drug resistance in ovarian cancer.Conclusion EFNA1 overexpression mediated platinum resistance and significantly associated with clinical parameters and prognosis in ovarian cancer.
关键词(KeyWords):
EFNA1;卵巢癌;铂类耐药
EFNA1;ovarian cancer;platinum resistance
基金项目(Foundation): 扬州市自然科学基金面上项目(YZ2017114)
作者(Author):
王可可,冉晓敏,严慧深,阎可,何亮
WANG Keke,RAN Xiaomin,YAN Huishen,YAN Ke,HE Liang
DOI: 10.14066/j.cnki.cn21-1349/r.2021.0681
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