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通过多种方法分选的卵巢癌细胞干细胞的常见遗传特征的综合分析。

Integrative analysis of the common genetic characteristics in ovarian cancer stem cells sorted by multiple approaches.

机构信息

Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv., Wuhan, 430030, Hubei, China.

Department of Gynecology and Obstetrics, The Central Hospital of Wuhan, Wuhan, Hubei, China.

出版信息

J Ovarian Res. 2020 Sep 25;13(1):116. doi: 10.1186/s13048-020-00715-7.

DOI:10.1186/s13048-020-00715-7
PMID:32977853
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7519480/
Abstract

BACKGROUND

Ovarian cancer is the second fatal malignancy of the female reproductive system. Based on the cancer stem cell (CSC) theory, its poor prognosis of ovarian cancer attributed to tumor recurrence caused by CSCs. A variety of cell surface-specific markers have been employed to identify ovarian cancer stem cells (OCSCs). In this study, we attempted to explore the common feature in ovarian cancer stem cells sorted by multiple approaches.

METHODS

We collected the gene expression profiles of OCSCs were from 5 public cohorts and employed R software and Bioconductor packages to establish differently expressed genes (DEGs) between OCSCs and parental cells. We extracted the integrated DEGs by protein-protein interaction (PPI) network construction and explored potential treatment by the Cellminer database.

RESULTS

We identified and integrated the DEGs of OCSCs sorted by multiple isolation approaches. Besides, we identified OCSCs share characteristics in the lipid metabolism and extracellular matrix changes. Moreover, we obtained 16 co-expressed core genes, such as FOXQ1, MMP7, AQP5, RBM47, ETV4, NPW, SUSD2, SFRP2, IDO1, ANPEP, CXCR4, SCNN1A, SPP1 and IFI27 (upregulated) and SERPINE1, DUSP1, CD40, and IL6 (downregulated). Through correlation analysis, we screened out ten potential drugs to target the core genes.

CONCLUSION

Based on the comprehensive analysis of the genomic datasets with different sorting methods of OCSCs, we figured out the common driving genes to regulating OCSC and obtained ten new potential therapies for eliminating ovarian cancer stem cells. Hence, the findings of our study might have potential clinical significance.

摘要

背景

卵巢癌是女性生殖系统第二大致命恶性肿瘤。基于癌症干细胞(CSC)理论,其预后不良归因于 CSCs 引起的肿瘤复发。已经采用了多种细胞表面特异性标记物来鉴定卵巢癌干细胞(OCSCs)。在这项研究中,我们试图探索通过多种方法分选的卵巢癌干细胞的共同特征。

方法

我们从 5 个公共队列中收集 OCSC 的基因表达谱,并使用 R 软件和 Bioconductor 软件包来建立 OCSC 与亲本细胞之间的差异表达基因(DEGs)。我们通过蛋白质-蛋白质相互作用(PPI)网络构建提取整合的 DEGs,并通过 Cellminer 数据库探索潜在的治疗方法。

结果

我们鉴定并整合了通过多种分离方法分选的 OCSC 的 DEGs。此外,我们发现 OCSC 在脂质代谢和细胞外基质变化方面具有共同特征。此外,我们获得了 16 个共表达的核心基因,如 FOXQ1、MMP7、AQP5、RBM47、ETV4、NPW、SUSD2、SFRP2、IDO1、ANPEP、CXCR4、SCNN1A、SPP1 和 IFI27(上调)和 SERPINE1、DUSP1、CD40 和 IL6(下调)。通过相关性分析,我们筛选出 10 种针对核心基因的潜在药物。

结论

基于不同分选方法的 OCSC 基因组数据集的综合分析,我们确定了调节 OCSC 的共同驱动基因,并获得了十种新的潜在治疗卵巢癌干细胞的方法。因此,我们的研究结果可能具有潜在的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/02131aabb325/13048_2020_715_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/2cb90b359257/13048_2020_715_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/8f36021b43ac/13048_2020_715_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/cdee0ac366b5/13048_2020_715_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/4d547bb67eb7/13048_2020_715_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/c695f0940c4b/13048_2020_715_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/26c5922e610f/13048_2020_715_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/6ad0df58ebd1/13048_2020_715_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/02131aabb325/13048_2020_715_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/2cb90b359257/13048_2020_715_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/8f36021b43ac/13048_2020_715_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/cdee0ac366b5/13048_2020_715_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/4d547bb67eb7/13048_2020_715_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/c695f0940c4b/13048_2020_715_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/26c5922e610f/13048_2020_715_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/6ad0df58ebd1/13048_2020_715_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a750/7519480/02131aabb325/13048_2020_715_Fig8_HTML.jpg

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