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基于单细胞 RNA 测序联合转录组分析鉴定的细胞间通讯相关分子亚型和基因特征。

Intercellular Communication-Related Molecular Subtypes and a Gene Signature Identified by the Single-Cell RNA Sequencing Combined with a Transcriptomic Analysis.

机构信息

Departments of Geriatrics Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China.

Spinal Surgery of Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China.

出版信息

Dis Markers. 2022 May 16;2022:6837849. doi: 10.1155/2022/6837849. eCollection 2022.

DOI:10.1155/2022/6837849
PMID:35620271
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9127593/
Abstract

BACKGROUND

The tumor microenvironment (TME) of lung adenocarcinoma (LUAD) comprise various cell types that communicate with each other through ligand-receptor interactions. This study focused on the identification of cell types in LUAD by single-cell RNA sequencing (scRNA-seq) data and screening of intercellular communication-related genes.

METHODS

The Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo) provided the RNA-seq data of LUAD patients in the GSE149655, GSE31210, and GSE72094 datasets. Quality control of the scRNA-seq data in GSE149655 was performed by the Seurat package (http://seurat.r-forge.r-project.org) for identifying highly variable genes for principal component analysis (PCA) and cell clustering. The CellPhoneDB (http://www.cellphonedb.org) was used for filtering intercellular communication-related ligand-receptor pairs. According to ligand and receptor expressions, LUAD samples were clustered using ConsensusClusterPlus (https://www.bioconductor.org/packages/release/bioc/html/ConsensusClusterPlus). Additionally, the identification of prognosis-related ligand and receptor genes was conducted along with the development of a risk prediction model by the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.

RESULTS

This study identified twelve cell types in 8170 cells of LUAD tissues along with 219 ligand and receptor genes. LUAD was classified into three different molecular subtypes, among which cluster 3 (C3) had the longest overall survival (OS) time and cluster (C1) had the shortest OS time. In comparison with the other two molecular subtypes, it was observed that C1 had a higher rate of somatic mutations and lower levels of infiltrating immune cells and immune scores. Ten genes were screened from the total ligand and receptor genes to construct a risk model, which showed a strong prediction power in the prognosis of patients with LUAD.

CONCLUSION

The results of this study revealed cell types specific to LUAD, which were classified into different molecular subtypes according to intercellular communication-related genes. A novel prognostic risk model was developed in this study, providing new insights into prognostic assessment models for LUAD.

摘要

背景

肺腺癌 (LUAD) 的肿瘤微环境 (TME) 由各种细胞类型组成,这些细胞通过配体-受体相互作用相互沟通。本研究通过单细胞 RNA 测序 (scRNA-seq) 数据鉴定 LUAD 中的细胞类型,并筛选细胞间通讯相关基因。

方法

Gene Expression Omnibus (GEO) 数据库 (https://www.ncbi.nlm.nih.gov/geo) 提供了 GSE149655、GSE31210 和 GSE72094 数据集的 LUAD 患者 RNA-seq 数据。通过 Seurat 包 (http://seurat.r-forge.r-project.org) 对 GSE149655 中的 scRNA-seq 数据进行质量控制,用于主成分分析 (PCA) 和细胞聚类的高变异基因识别。使用 CellPhoneDB (http://www.cellphonedb.org) 筛选细胞间通讯相关的配体-受体对。根据配体和受体的表达情况,使用 ConsensusClusterPlus (https://www.bioconductor.org/packages/release/bioc/html/ConsensusClusterPlus) 对 LUAD 样本进行聚类。此外,通过最小绝对收缩和选择算子 (LASSO) Cox 回归分析,进行与预后相关的配体和受体基因的鉴定,并建立风险预测模型。

结果

本研究在 8170 个 LUAD 组织细胞中鉴定出 12 种细胞类型和 219 个配体-受体基因。LUAD 分为三个不同的分子亚型,其中 3 型 (C3) 的总生存时间最长,1 型 (C1) 的总生存时间最短。与其他两个分子亚型相比,C1 具有更高的体细胞突变率和更低的浸润免疫细胞和免疫评分。从总配体和受体基因中筛选出 10 个基因构建风险模型,该模型在 LUAD 患者的预后预测中具有较强的预测能力。

结论

本研究揭示了 LUAD 特异的细胞类型,并根据细胞间通讯相关基因将其分为不同的分子亚型。本研究建立了一种新的预后风险模型,为 LUAD 的预后评估模型提供了新的见解。

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