2023 World Conference on Lung Cancer (Posters)-EP03.03. Single-nucleus RNA Sequencing Dissecting the Tumor Microenvironment of Liver Metastasis of Non-small Cell Lung Cancer

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Liver metastasis is a crucial factor that affects the survival of patients with non-small cell lung cancer (NSCLC) and limits the effectiveness of various treatment approaches. However, the detailed mechanisms underlying liver metastasis, particularly the complex tumor microenvironment, remain unclear. In this study, researchers used single-nucleus RNA sequencing to analyze the transcriptomic heterogeneity of liver metastatic tumors in NSCLC patients compared to healthy liver tissues. This approach provided insights into potential mechanisms of liver metastasis.<br /><br />The study involved sequencing biopsy samples from three NSCLC patients with liver metastasis. After quality control, a total of 47,339 cells were included for analysis. Additionally, single-nucleus RNA sequencing data from three healthy liver tissues were downloaded from a database for comparison. The researchers used bioinformatic tools to classify the cells into different clusters and labeled them based on known markers.<br /><br />The analysis revealed 17 clusters, with clusters 16 and 17 exclusively found in liver metastasis samples. Compared to healthy liver tissues, liver metastasis samples had more epithelial cells (including tumor cells) but fewer hepatocytes. Surprisingly, there were more Kupffer cells, endothelial cells, T cells, and B cells in liver metastasis samples compared to healthy liver tissues. Enrichment analysis identified specific genes associated with liver metastasis, including PRRC2B, HEPACAM2, KIT, and MMP9.<br /><br />Further analysis at the single-cell level revealed differences in gene expression between liver metastasis and healthy liver tissues. MMP7, SPP1, and S100A10 were significantly enriched in liver metastasis Kupffer cells, while IGF2, AREG, CD68, and FGL1 were enriched in healthy liver Kupffer cells. T cells in liver metastasis showed a more suppressive phenotype, with GSTA1, PRRC2B, CD74, and S100A11 highly expressed.<br /><br />Gene set enrichment analysis revealed various pathways that were enriched in the liver metastasis microenvironment compared to healthy controls, such as the ribosome, complement and coagulation cascades in Kupffer cells, and the Wnt signaling pathway in T cells.<br /><br />Overall, this study provides a comprehensive analysis of the transcriptome of the liver metastasis tumor microenvironment in NSCLC patients. These findings enhance our understanding of the underlying mechanisms of liver metastasis in NSCLC and may contribute to the development of targeted therapeutic strategies.

Asset Subtitle

Jie Huang

Meta Tag

Speaker Jie Huang

Topic Tumor Biology: Translational Biology - IO

Keywords

Liver metastasis

non-small cell lung cancer

tumor microenvironment

single-nucleus RNA sequencing

transcriptomic heterogeneity

biopsy samples

epithelial cells

Kupffer cells

T cells

Wnt signaling pathway