Transcriptional profile of tumor hybrid cells associated with non-small cell lung cancer progression at the single cell level

Tumor hybrid cells (THCs) are considered key contributors to cancer progression due to their proliferative activity, immune evasion, and therapy resistance. In our previous study, we identified THCs associated with the risk of hematogenous metastasis and locoregional recurrence in non-small cell lung cancer (NSCLC). However, the molecular factors underlying this association remain unclear. The aim of the present study was to investigate the transcriptional profiles of THCs associated with metastasis and recurrence in NSCLC. The analysis included transcriptomic data from primary tumor cells obtained from 102 NSCLC patients from the open-access single-cell RNA sequencing atlas. The Seurat package was used to identify THCs and analyze their transcriptional profiles, while clusterProfiler was applied to assess functional enrichment of signaling pathways and biological processes. Metastasis-associated THCs exhibited differential expression of genes involved in epithelial-mesenchymal transition (EMT) and energy metabolism, whereas recurrence-associated THCs were enriched with glucose metabolism, EMT, and maintenance of a stem-like phenotype. These findings provide new insights into the transcriptional characteristics of THCs associated with NSCLC progression.

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