Research Paper Volume 15, Issue 12 pp 5339—5354
Heterogeneity of tumor immune microenvironment in malignant and metastatic change in LUAD is revealed by single-cell RNA sequencing
- 1 Department of Thoracic Surgery, Tangdu Hospital Air Force Medical University, Fourth Military Medical University, Xian, Shanxi, China
Received: February 10, 2023 Accepted: May 9, 2023 Published: June 16, 2023
https://doi.org/10.18632/aging.204752How to Cite
Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.