Single-cell transcriptomics reveals the multidimensional dynamic heterogeneity from primary to metastatic gastric...

Reprogramming of the tumor microenvironment (TME) plays a critical role in gastric cancer (GC) progression and metastasis. However, the multidimensional features between primary tumors and organ-specific metastases remain poorly understood. In this study, we characterized the dynamic heterogeneity of GC from primary to metastatic stages. We identified seven major cell types and 27 immune and stromal subsets. Immune cells decreased, while immunosuppressive cells increased in ovarian and peritoneal metastases. A 30-gene signature for ovarian metastasis was validated in GC cohorts. Additionally, critical ligand-receptor interactions, including LGALS9-MET in liver metastasis and PVR-TIGIT in lymph node metastasis, were identified as potential therapeutic targets. Furthermore, CLOCK, a transcription factor, was associated with poor prognosis and influenced immune cell interactions and migration. Collectively, this study provides valuable insights into TME dynamics in GC and highlights potential avenues for targeted therapies.