Identifying genes as potential prognostic indicators in patients with serous ovarian cancer resistant to carboplatin using integrated bioinformatics analysis.

Identifying genes as potential prognostic indicators in patients with serous ovarian cancer resistant to carboplatin using integrated bioinformatics analysis.
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使用综合生物信息学分析将基因识别为对卡铂耐药的浆液性卵巢癌患者的潜在预后指标

DOI:
10.3892/or.2018.6383
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发表时间:
2018-06
期刊:
影响因子:
4.2
通讯作者:
Linghu H
Linghu H
中科院分区:
医学3区
文献类型:
--
作者:
Zhan SJ;Liu B;Linghu H

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浆液性卵巢癌(SOC)占所有上皮性卵巢癌的50%。然而,SOC患者对以铂为基础的化疗表现出不同程度的反应,因此,他们的存活率可能不同。本研究旨在通过分析微阵列数据集GDS 1381和GDS 3592来确定与SOC的致癌和耐药相关的候选基因。GDS 1381和GDS 3592从基因表达总览数据库()下载。共鉴定出219个差异表达基因(Deg)。分析了可能预测卡铂疗效和预测SOC预后的潜在基因。DEGS丰富的功能和途径包括胞外区、胞外间隙和胞外外体等。通过筛选连接图上上调和下调的基因,确定了10种可能有助于提高卵巢癌患者药物敏感性的小分子药物。构建蛋白质-蛋白质相互作用网络后,共筛选出30个Hub基因进行进一步分析。通过生存分析、基因比对和免疫组织化学方法,确定GNAI1、染色体非结构维持(Non-SMC)、凝聚素I复合体H(NCAPH)、基质金属多肽酶9(MMP9)、极光激酶A(AURKA)和ZEST2多梳抑制复合体2亚单位增强子(EZH2)可能与SOC的致癌和卡铂耐药有关。综上所述,GNAI1、NCAPH、MMP9、AURKA和EZH2参与SOC的致癌和卡铂反应的可能性有待进一步研究。
Serous ovarian cancer (SOC) accounts for >50% of all epithelial ovarian cancers. However, patients with SOC present with various degrees of response to platinum-based chemotherapy and, thus, their survival may differ. The present study aimed to identify the candidate genes involved in the carcinogenesis and drug resistance of SOC by analyzing the microarray datasets GDS1381 and GDS3592. GDS1381 and GDS3592 were downloaded from the Gene Expression Omnibus database (). A total of 219 differentially expressed genes (DEGs) were identified. Potential genes that may predict the response to carboplatin and, thus, the prognosis of SOC were analyzed. The enriched functions and pathways of DEGs included extracellular region, extracellular space and extracellular exosome, among others. Upon screening the upregulated and downregulated genes on the connectivity map, 10 small-molecule drugs were identified that may be helpful in improving drug sensitivity in patients with ovarian cancer. A total of 30 hub genes were screened for further analysis after constructing the protein-to-protein interaction network. Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non-structural maintenance of chromosomes (non-SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC.
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