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基于单细胞RNA测序数据集鉴定胃癌中与肿瘤微环境相关的新基因。

Identification of novel tumor microenvironment-associated genes in gastric cancer based on single-cell RNA-sequencing datasets.

作者信息

Wei Xujin, Liu Jie, Hong Zhijun, Chen Xin, Wang Kang, Cai Jianchun

机构信息

The Graduate School of Fujian Medical University, Fuzhou, China.

Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen, China.

出版信息

Front Genet. 2022 Aug 15;13:896064. doi: 10.3389/fgene.2022.896064. eCollection 2022.

Abstract

Tumor microenvironment and heterogeneity play vital roles in the development and progression of gastric cancer (GC). In the past decade, a considerable amount of single-cell RNA-sequencing (scRNA-seq) studies have been published in the fields of oncology and immunology, which improve our knowledge of the GC immune microenvironment. However, much uncertainty still exists about the relationship between the macroscopic and microscopic data in transcriptomics. In the current study, we made full use of scRNA-seq data from the Gene Expression Omnibus database (GSE134520) to identify 25 cell subsets, including 11 microenvironment-related cell types. The MIF signaling pathway network was obtained upon analysis of receptor-ligand pairs and cell-cell interactions. By comparing the gene expression in a wide variety of cells between intestinal metaplasia and early gastric cancer, we identified 64 differentially expressed genes annotated as immune response and cellular communication. Subsequently, we screened these genes for prognostic clinical value based on the patients' follow-up data from The Cancer Genome Atlas. and were then selected for the construction of LASSO risk scores, and a nomogram model incorporating another five clinical risk factors was successfully created. The effectiveness of least absolute shrinkage and selection operator risk scores was validated using gene set enrichment analysis and levels of immune cell infiltration. These findings will drive the development of prognostic evaluations affected by the immune tumor microenvironment in GC.

摘要

肿瘤微环境和异质性在胃癌(GC)的发生发展过程中起着至关重要的作用。在过去十年中,肿瘤学和免疫学领域发表了大量的单细胞RNA测序(scRNA-seq)研究,这些研究增进了我们对GC免疫微环境的了解。然而,转录组学中宏观和微观数据之间的关系仍存在许多不确定性。在本研究中,我们充分利用来自基因表达综合数据库(GSE134520)的scRNA-seq数据,鉴定出25个细胞亚群,包括11种与微环境相关的细胞类型。通过分析受体-配体对和细胞间相互作用,获得了MIF信号通路网络。通过比较肠化生和早期胃癌中多种细胞的基因表达,我们鉴定出64个差异表达基因,这些基因被注释为免疫反应和细胞通讯相关基因。随后,我们根据癌症基因组图谱中患者的随访数据,筛选这些基因的预后临床价值。然后选择 和 构建LASSO风险评分,并成功创建了一个纳入另外五个临床风险因素的列线图模型。使用基因集富集分析和免疫细胞浸润水平验证了最小绝对收缩和选择算子风险评分的有效性。这些发现将推动受GC免疫肿瘤微环境影响的预后评估的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dce/9421061/5e6431be5207/fgene-13-896064-g001.jpg

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