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生物信息学分析浆液性卵巢癌基因表达谱,筛选关键基因和通路。

Bioinformatics analysis of gene expression profile of serous ovarian carcinomas to screen key genes and pathways.

机构信息

Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory of Embryo Original Diseases, Shanghai Municipal Key Clinical Specialty, Shanghai Jiao Tong University School of Medicine, No.910, Hengshan Road, Shanghai, 200030, People's Republic of China.

出版信息

J Ovarian Res. 2020 Jul 21;13(1):82. doi: 10.1186/s13048-020-00680-1.

Abstract

BACKGROUND

Serous ovarian carcinomas (SCA) are the most common and most aggressive ovarian carcinoma subtype which etiology remains unclear. To investigate the prospective role of mRNAs in the tumorigenesis and progression of SCA, the aberrantly expressed mRNAs were calculated based on the NCBI-GEO RNA-seq data.

RESULTS

Of 21,755 genes with 89 SCA and SBOT cases from 3 independent laboratories, 59 mRNAs were identified as differentially expressed genes (DEGs) (|logFold Change| > 1.585, also |FoldChange| > 3 and adjusted P < 0.05) by DESeq R. There were 26 up-regulated DEGs and 33 down-regulated DEGs screened. The hierarchical clustering analysis, functional analysis and pathway enrichment analysis were performed on all DEGs and found that Polo-like kinase (PLK) signaling events are important. PPI network constructed with different filtration conditions screened out 4 common hub genes (KIF11, CDC20, PBK and TOP2A). Mutual exclusivity or co-occurrence analysis of 4 hub genes identified a tendency towards co-occurrence between KIF11 and CDC20 or TOP2A in SCA (p < 0.05). To analyze further the potential role of KIF11 in SCA, the co-expression profiles of KIF11 in SCA were identified and we found that CDC20 co-expressed with KIF11 also is DEG that we screened out before. To verify our previous results in this paper, we assessed the expression levels of 4 hub DEGs (all up-regulated) and 4 down-regulated DEGs in Oncomine database. And the results were consistent with previous conclusions obtained from GEO series. The survival curves showed that KIF11, CDC20 and TOP2A expression are significantly related to prognosis of SCA patients.

CONCLUSIONS

From all the above results, we speculate that KIF11, CDC20 and TOP2A played an important role in SCA.

摘要

背景

浆液性卵巢癌(SCA)是最常见和最具侵袭性的卵巢癌亚型,其病因尚不清楚。为了研究 mRNAs 在 SCA 发生和进展中的潜在作用,基于 NCBI-GEO RNA-seq 数据计算了异常表达的 mRNAs。

结果

在来自 3 个独立实验室的 89 例 SCA 和 SBOT 病例的 21755 个基因中,通过 DESeq R 鉴定出 59 个差异表达基因(|logFold Change| > 1.585,|FoldChange| > 3,调整 P < 0.05)。筛选出 26 个上调的 DEGs 和 33 个下调的 DEGs。对所有 DEGs 进行了层次聚类分析、功能分析和通路富集分析,发现 Polo 样激酶(PLK)信号事件很重要。使用不同过滤条件构建的 PPI 网络筛选出 4 个常见的 hub 基因(KIF11、CDC20、PBK 和 TOP2A)。对 4 个 hub 基因的互斥或共发生分析表明,KIF11 和 CDC20 或 TOP2A 在 SCA 中存在共发生的趋势(p < 0.05)。为了进一步分析 KIF11 在 SCA 中的潜在作用,我们确定了 SCA 中 KIF11 的共表达谱,我们发现与 KIF11 共表达的 CDC20 也是我们之前筛选出的 DEG。为了验证本文中的先前结果,我们在 Oncomine 数据库中评估了 4 个 hub DEG(均上调)和 4 个下调 DEG 的表达水平。结果与从 GEO 系列获得的先前结论一致。生存曲线表明,KIF11、CDC20 和 TOP2A 的表达与 SCA 患者的预后显著相关。

结论

综上所述,我们推测 KIF11、CDC20 和 TOP2A 在 SCA 中发挥重要作用。

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