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基于单细胞 RNA 测序的肺癌免疫细胞浸润特征及相关标记基因。

Immune cell infiltration features and related marker genes in lung cancer based on single-cell RNA-seq.

机构信息

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Huaihai West Road No. 241, Shanghai, 200030, China.

出版信息

Clin Transl Oncol. 2021 Feb;23(2):405-417. doi: 10.1007/s12094-020-02435-2. Epub 2020 Jul 12.

DOI:10.1007/s12094-020-02435-2
PMID:32656582
Abstract

PURPOSE

Immune cells in the immune microenvironment of lung cancer have a great impact on the development of lung cancer. Our purpose was to analyze the immune cell infiltration features and related marker genes for lung cancer.

METHODS

Single cell RNA sequencing data of 11,485 lung cancer cells were retrieved from the Gene Expression Omnibus. After quality control and data normalization, cell clustering was performed using the Seurat package. Based on the marker genes of each cell type from the CellMarker database, each cell was divided into G1, G2M, and S phases. Then, differential expression and functional enrichment analyses were performed. CIBERSORT was used to reconstruct immune cell types.

RESULTS

Following cell filtering, highly variable genes were identified for all cells. 14 cell types were clustered. Among them, CD4 + T cell, B cell, plasma cell, natural killer cell and cancer stem cell were the top five cell types. Up-regulated genes were mainly enriched in immune-related biological processes and pathways. Using CIBERSORT, we identified the significantly higher fractions of naïve B cell, memory CD4 + T cell, T follicular helper cell, T regulatory helper cell and M1 macrophage in lung cancer tissues compared to normal tissues. Furthermore, the fractions of resting NK cell, monocyte, M0 macrophage, resting mast cell, eosinophil and neutrophil were significantly lower in tumor tissues than normal tissues.

CONCLUSION

Our findings dissected the immune cell infiltration features and related marker genes for lung cancer, which might provide novel insights for the immunotherapy of lung cancer.

摘要

目的

肺癌免疫微环境中的免疫细胞对肺癌的发生发展有重要影响。本研究旨在分析肺癌的免疫细胞浸润特征及相关标记基因。

方法

从基因表达综合数据库中检索了 11485 个肺癌细胞的单细胞 RNA 测序数据。经过质量控制和数据归一化后,使用 Seurat 包进行细胞聚类。基于 CellMarker 数据库中每个细胞类型的标记基因,将每个细胞分为 G1、G2M 和 S 期。然后进行差异表达和功能富集分析。使用 CIBERSORT 重建免疫细胞类型。

结果

经过细胞过滤后,确定了所有细胞的高变基因。聚类出 14 种细胞类型。其中,CD4+T 细胞、B 细胞、浆细胞、自然杀伤细胞和癌症干细胞是前 5 种细胞类型。上调基因主要富集在免疫相关的生物学过程和途径中。使用 CIBERSORT,我们发现与正常组织相比,肺癌组织中幼稚 B 细胞、记忆性 CD4+T 细胞、滤泡辅助性 T 细胞、调节性辅助性 T 细胞和 M1 巨噬细胞的比例明显更高。此外,肿瘤组织中静止 NK 细胞、单核细胞、M0 巨噬细胞、静止肥大细胞、嗜酸性粒细胞和中性粒细胞的比例明显低于正常组织。

结论

本研究剖析了肺癌的免疫细胞浸润特征及相关标记基因,可能为肺癌的免疫治疗提供新的思路。

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