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单细胞 RNA 测序揭示 LUAD 恶性和转移变化中肿瘤免疫微环境的异质性。

Heterogeneity of tumor immune microenvironment in malignant and metastatic change in LUAD is revealed by single-cell RNA sequencing.

机构信息

Department of Thoracic Surgery, Tangdu Hospital Air Force Medical University, Fourth Military Medical University, Xian, Shanxi, China.

出版信息

Aging (Albany NY). 2023 Jun 16;15(12):5339-5354. doi: 10.18632/aging.204752.


DOI:10.18632/aging.204752
PMID:37335089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10333068/
Abstract

Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer and accounts for approximately 40% of all lung cancer cases. Multiple distant metastases are the major cause of mortality in lung cancer. In this study, single-cell sequencing datasets of LUAD were utilized to depict the transcriptome characteristic of LUAD based on the bioinformatic method. Firstly, the transcriptome landscape of heterogeneous cell types in LUAD was analyzed and memory T cells, NK cells, and helper T cells were revealed to be the common immune cells in tumor, normal, and metastasis tissue, respectively. Then, marker genes were calculated and 709 genes were identified to play a vital role in the microenvironment of LUAD. While macrophages were reported to act as one of the cells in LUAD, enrichment analysis of macrophage marker genes revealed the important role of macrophages in the activation of neutrophils. Next, the results of cell-cell communication analysis suggested that pericytes interact with broad immune cells via MDK-NCL pathways in metastasis samples, MIF-(CD74+CXCR4) and MIF-(CD74+CC44) interaction especially occurred between different cell types in tumor and normal samples. Finally, bulk RNA-seq was integrated to validate the prognosis effect of the marker gene and the maker gene of M2 macrophage, CCL20, showed the most related to LUAD prognosis. Besides, ZNF90 (Helper T cells), FKBP4 (memory T, helper T, Cytotoxic T, and B cells), CD79A (B cells), TPI1 (pericyte), and HOPX (epithelial cells, pericytes) were also pivotal in the pathology of LUAD, helping researchers understand the molecular insight of microenvironment in LUAD.

摘要

肺腺癌 (LUAD) 是最常见的非小细胞肺癌类型,约占所有肺癌病例的 40%。远处转移是肺癌患者死亡的主要原因。本研究利用 LUAD 的单细胞测序数据集,采用生物信息学方法描绘 LUAD 的转录组特征。首先,分析 LUAD 异质性细胞类型的转录组图谱,揭示记忆 T 细胞、NK 细胞和辅助 T 细胞分别为肿瘤、正常和转移组织中的常见免疫细胞。然后,计算标记基因并鉴定出 709 个对 LUAD 微环境起重要作用的基因。虽然巨噬细胞被报道为 LUAD 中的一种细胞,但巨噬细胞标记基因的富集分析揭示了巨噬细胞在中性粒细胞激活中的重要作用。接下来,细胞间通讯分析的结果表明,在转移样本中,周细胞通过 MDK-NCL 途径与广泛的免疫细胞相互作用,MIF-(CD74+CXCR4)和 MIF-(CD74+CC44)相互作用特别发生在肿瘤和正常样本中的不同细胞类型之间。最后,整合批量 RNA-seq 验证了标记基因的预后效应,M2 巨噬细胞的标记基因 CCL20 与 LUAD 预后最相关。此外,ZNF90(辅助 T 细胞)、FKBP4(记忆 T、辅助 T、细胞毒性 T 和 B 细胞)、CD79A(B 细胞)、TPI1(周细胞)和 HOPX(上皮细胞、周细胞)在 LUAD 病理中也至关重要,有助于研究人员了解 LUAD 微环境的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/3cea7905db05/aging-15-204752-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/c2a5c9f20d32/aging-15-204752-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/1da6d598dbe6/aging-15-204752-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/2ea5022fa456/aging-15-204752-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/9a4b37f6c156/aging-15-204752-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/9613585c7ed2/aging-15-204752-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/81cf420e980c/aging-15-204752-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/3cea7905db05/aging-15-204752-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/c2a5c9f20d32/aging-15-204752-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/80691ef6fa56/aging-15-204752-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/1da6d598dbe6/aging-15-204752-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/2ea5022fa456/aging-15-204752-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/9a4b37f6c156/aging-15-204752-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/9613585c7ed2/aging-15-204752-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/81cf420e980c/aging-15-204752-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d332/10333068/3cea7905db05/aging-15-204752-g008.jpg

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本文引用的文献

[1]
Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma.

Clin Transl Med. 2023-3

[2]
Identification of OTUD6B as a new biomarker for prognosis and immunotherapy by pan-cancer analysis.

Front Immunol. 2022

[3]
The expression of POSTN and immune cell infiltration are prognostic factors of lung adenocarcinoma.

Medicine (Baltimore). 2022-8-26

[4]
The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing.

Signal Transduct Target Ther. 2022-8-26

[5]
CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition.

Int J Biol Sci. 2022

[6]
Identification and Validation of a Novel Signature Based on NK Cell Marker Genes to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma by Integrated Analysis of Single-Cell and Bulk RNA-Sequencing.

Front Immunol. 2022

[7]
Typical tumor immune microenvironment status determine prognosis in lung adenocarcinoma.

Transl Oncol. 2022-4

[8]
Integrated analysis of single-cell and bulk RNA-sequencing identifies a signature based on B cell marker genes to predict prognosis and immunotherapy response in lung adenocarcinoma.

Cancer Immunol Immunother. 2022-10

[9]
Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma.

J Immunother Cancer. 2022-1

[10]
Three Differential Expression Analysis Methods for RNA Sequencing: limma, EdgeR, DESeq2.

J Vis Exp. 2021-9-18

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