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基于肝内胆管癌免疫细胞单细胞RNA测序数据的预后特征的开发

Development of a Prognostic Signature Based on Single-Cell RNA Sequencing Data of Immune Cells in Intrahepatic Cholangiocarcinoma.

作者信息

Su Miao, Qiao Kuang-Yuan, Xie Xiao-Li, Zhu Xin-Ying, Gao Fu-Lai, Li Chang-Juan, Zhao Dong-Qiang

机构信息

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Gastroenterology, Hengshui People's Hospital, Hengshui, China.

出版信息

Front Genet. 2021 Feb 4;11:615680. doi: 10.3389/fgene.2020.615680. eCollection 2020.

Abstract

Analysis of single-cell RNA sequencing (scRNA-seq) data of immune cells from the tumor microenvironment (TME) may identify tumor progression biomarkers. This study was designed to investigate the prognostic value of differentially expressed genes (DEGs) in intrahepatic cholangiocarcinoma (ICC) using scRNA-seq. We downloaded the scRNA-seq data of 33,991 cell samples, including 17,090 ICC cell samples and 16,901 ICC adjacent tissue cell samples regarded as normal cells. scRNA-seq data were processed and classified into 20 clusters. The immune cell clusters were extracted and processed again in the same way, and each type of immune cells was divided into several subclusters. In total, 337 marker genes of macrophages and 427 marker genes of B cells were identified by comparing ICC subclusters with normal subclusters. Finally, 659 DEGs were obtained by merging B cell and macrophage marker genes. ICC sample clinical information and gene expression data were downloaded. A nine-prognosis-related-gene (PRG) signature was established by analyzing the correlation between DEGs and overall survival in ICC. The robustness and validity of the signature were verified. Functional enrichment analysis revealed that the nine PRGs were mainly involved in tumor immune mechanisms. In conclusion, we established a PRG signature based on scRNA-seq data from immune cells of patients with ICC. This PRG signature not only reflects the TME immune status but also provides new biomarkers for ICC prognosis.

摘要

对肿瘤微环境(TME)中免疫细胞的单细胞RNA测序(scRNA-seq)数据进行分析,可能会识别出肿瘤进展的生物标志物。本研究旨在利用scRNA-seq研究肝内胆管癌(ICC)中差异表达基因(DEG)的预后价值。我们下载了33991个细胞样本的scRNA-seq数据,其中包括17090个ICC细胞样本和16901个被视为正常细胞的ICC癌旁组织细胞样本。scRNA-seq数据经过处理后被分类为20个簇。对免疫细胞簇进行提取并以同样的方式再次处理,每种免疫细胞被分为几个亚簇。通过将ICC亚簇与正常亚簇进行比较,共鉴定出337个巨噬细胞标记基因和427个B细胞标记基因。最后,通过合并B细胞和巨噬细胞标记基因获得了659个DEG。下载了ICC样本的临床信息和基因表达数据。通过分析DEG与ICC总生存期之间的相关性,建立了一个九预后相关基因(PRG)特征。验证了该特征的稳健性和有效性。功能富集分析表明,这九个PRG主要参与肿瘤免疫机制。总之,我们基于ICC患者免疫细胞的scRNA-seq数据建立了一个PRG特征。这个PRG特征不仅反映了TME免疫状态,也为ICC预后提供了新的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0712/7890365/65a1d65de799/fgene-11-615680-g0001.jpg

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