Identification of cancer stem cell-related biomarkers in intestinal-type and diffuse-type gastric cancer by stemness index and weighted correlation network analysis.

Identification of cancer stem cell-related biomarkers in intestinal-type and diffuse-type gastric cancer by stemness index and weighted correlation network analysis.
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DOI:
10.1186/s12967-020-02587-3
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发表时间:
2020-11-07
影响因子:
7.4
通讯作者:
Gong Y
Gong Y
中科院分区:
医学2区
文献类型:
--
作者:
Guo R;Chu A;Gong Y

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肿瘤干细胞(cancer stem cells,CSCs)在肿瘤的耐药、复发和转移中起着重要作用。鉴于肿瘤的异质性,本研究旨在探讨胃癌浸润型和弥漫型干细胞调控的关键基因。RNA-seq数据和相关临床信息从The Cancer Genome Atlas(TCGA)下载。WGCNA用于聚类具有相似表达谱的差异表达基因以形成模块。基于mRNA表达量的茎干指数(mRNAsi),进一步确定了重要模块和关键基因。接下来,通过Oncomine数据库进一步验证关键基因的表达。胃癌组织的MRNAsi评分明显高于正常组织。此外,弥漫型胃癌(DGC)的mRNAsi评分显著高于弥漫型胃癌(IGC)。WGCNA结果显示IGC的蓝色模块和DGC的棕色模块与mRNAsi的相关性最显著。筛选出16个IGC和43个DGC的关键基因,发现这些基因分别与IGC和DGC密切相关。功能分析显示了Oncomine数据库中确认的关键基因与细胞命运之间的关系。本研究在IGC和DGC中分别鉴定了16个和43个与CSC特性相关的基因。这些基因都与细胞周期相关,可以作为抑制两种类型GC干细胞的治疗靶点。
Cancer stem cells (CSCs) play an important role in drug resistance, recurrence, and metastasis of tumors. Considering the heterogeneity of tumors, this study aimed to explore the key genes regulating stem cells in intestinal-type and diffuse-type gastric cancer. RNA-seq data and related clinical information were downloaded from The Cancer Genome Atlas (TCGA). WGCNA was used to clustered differentially expressed genes with similar expression profiles to form modules. Furtherly, based on the mRNA expression-based stemness index (mRNAsi), significant modules and key genes were identified. Next, the expression of key genes was further verified by the Oncomine database. MRNAsi scores of GC were significantly higher than that of normal tissue. Additionally, mRNAsi scores of intestinal-type GC (IGC) were significantly higher than that of diffuse-type GC (DGC). WGCNA showed that the blue module of IGC and the brown module of DGC were both the most significantly associated with mRNAsi. We screened out 16 and 43 key genes for IGC and DGC and found that these genes were closely related, respectively. Functional analysis showed the relationship between the key genes confirmed in the Oncomine database and the fate of cells. In this study, 16 and 43 genes related to the characteristics of CSCs were identified in IGC and DGC, respectively. These genes were both associated with cell cycle, which could serve as therapeutic targets for the inhibition of stem cells from both types of GC.
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