Immune perturbation network identifies an EMT subtype with chromosomal instability and tumor immune-desert microenvironment.

Most gastric cancer (GC) subtypes are identified through transcriptional profiling overlooking dynamic changes and interactions in gene expression. Based on the background network of global immune genes, we constructed sample-specific edge-perturbation matrices and identified four molecular network subtypes of GC (MNG). MNG-1 displayed the best prognosis and vigorous cell cycle activity. MNG-2 was enriched by immune-hot phenotype with the potential for immunotherapy response. MNG-3 and MNG-4 were identified with epithelial-mesenchymal transition (EMT) peculiarity and worse prognosis, termed EMT subtypes. MNG-3 was characterized by low mutational burden and stromal cells and considered a replica of previous subtypes associated with poor prognosis. Notably, MNG-4 was considered a previously undefined subtype with a dismal prognosis, characterized by chromosomal instability and immune-desert microenvironment. This subtype tended to metastasize and was resistant to respond to immunotherapy. Pharmacogenomics analysis showed three therapeutic agents (NVP-BEZ235, LY2606368, and rutin) were potential interventions for MNG-4.