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Updated: Jul 11, 2025
Multidimensional Coculture System to Model Lung Squamous Carcinoma Progression
Published on: March 17, 2020
Multidimensional progressive single-cell sequencing reveals cell microenvironment composition and cancer
Hua Chen1,2, Anqi Song3, Faisal Ul Rehman4
1Department of Research and Development, Qingdao Bioman Biomedical Technology Co., LTD, Qingdao, China.
Abstract:
Despite substantial advances in cancer biology and treatment, the clinical outcomes of patients with lung cancer remain unsatisfactory. The tumor microenvironment (TME) is a potential target. Using single-cell RNA sequencing, we could distinguish eight distinct cell types in the lung cancer microenvironment, demonstrating substantial intratumoral heterogeneity in 19 different lung cancer tumor samples. Through the re-dimensional grouping of cancer-associated fibroblasts (CAFs), myeloid cells, epithelial cells, natural killer (NK) cells, and T cells, the difference in the TME of lung cancer was revealed. We discovered SFTPB, SFN, and KRT8 as possible predictive biomarkers for lung cancer by assessing the gene expression patterns in epithelial cells. Examining cell-to-cell communications showed a robust association between the quantity of matrix CAFs, epithelial cells, and macrophages in the thrombospondin signaling pathway. Additionally, we found that the amyloid precursor protein signaling pathway primarily originated from the matrix, and inflammatory cancer-associated endothelial and fibroblast cells showed a co-expression relationship with myeloid cells and B cells. Through cell-to-cell correlation analysis, we found positive regulation between NK cells, regulatory T cells, GZMB-CD8 T cells, and GZMK-CD8 T cells, which could play a role in developing immune TMEs. These findings support studies on cancer heterogeneity and add to our understanding of lung cancer's cellular microenvironment.
Insights
This study reveals significant lung cancer heterogeneity by analyzing the tumor microenvironment (TME) using single-cell RNA sequencing. Key biomarkers and cell communication pathways were identified, offering new insights into lung cancer progression.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Lung cancer treatment outcomes remain suboptimal despite advances in cancer biology.
- The tumor microenvironment (TME) presents a promising target for therapeutic intervention.
- Understanding intratumoral heterogeneity is crucial for developing effective lung cancer strategies.
Purpose of the Study:
- To characterize the cellular composition and heterogeneity of the lung cancer TME.
- To identify potential predictive biomarkers within the lung cancer microenvironment.
- To elucidate cell-to-cell communication networks within the TME.
Main Methods:
- Single-cell RNA sequencing was performed on 19 lung cancer tumor samples.
- Dimensionality reduction and cell type classification identified eight distinct cell populations.
- Gene expression patterns and cell-cell communication analyses were conducted.
Main Results:
- Eight distinct cell types were identified, highlighting substantial intratumoral heterogeneity.
- SFTPB, SFN, and KRT8 were identified as potential predictive biomarkers in epithelial cells.
- Key cell-cell communication pathways (thrombospondin, amyloid precursor protein) and immune cell interactions were elucidated.
Conclusions:
- The study provides a detailed cellular map of the lung cancer TME, revealing significant heterogeneity.
- Identified biomarkers and communication pathways offer potential targets for lung cancer diagnosis and therapy.
- Findings contribute to a deeper understanding of immune cell roles and interactions within the lung cancer microenvironment.
