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Background: Bone and brain metastasis are common in the NSCLC, and tumor environment has played a vital role in the metastasis, endothelial cells are a key component of the tumor microenvironment and its role in the development need to be investigated.

Methods: We collected three scRNA‑Seq datasets: GSE254379, GSE131907 and GSE225209 associated with the metastasis of lung cancer, and we integrated three datasets. Dimensionality reduction, clustering, and visualization (t - SNE, UMAP) were conducted, leading to the annotation of six major cell types (T cells, B/plasma cells, ECs, myeloid cells, fibroblasts, epithelial cells) using canonical markers. Subpopulation analysis, differential gene expression, and enrichment analysis were performed for each major cell type using the SCP package, with cell clusters annotated via established marker databases (CellMarker, PanglaoDB). The distribution preference of cell categories across tissues was assessed using odds ratios. Cell-cell communication was inferred using CellChat, analysing multiple signalling categories.

Results: We integrated three single-cell databases of metastasis-related NSCLC (GSE254379, GSE131907 and GSE225209). And we found that he arterial ECs, CD8 + T cycling T cells, MZB1 + plasma cells, MMP9 + macrophages were most associated with the bone metastasis. The CD8 + T GZMB cells, RPL + B cells, RPL + B cells were more abundant in the brain metastasis tissue. Compared with other immune cells, bidirectional interactions became much more in ECs and B cells. In cellular interactions, APP-CD74 plays an important role in immune cells and tumors.

Conclusion: APP - CD74 might mediate B cells and endothelial cells to play a vital role in tumor development.