The IGF2BP2 and FAM83A expression-positive malignant cell subpopulations identified in this study provide cytological insights into the development of LUAD, where the LUAD_IGF2BP2 subpopulation predominates in metastatic LUAD and is involved in vesicle synthesis, signaling molecule secretion, and exosome-related biological functions, from which we suggested that tumor microenvironment reprogramming during the malignant evolution of metastatic LUAD involves intercellular communication with exosomes as the main means. The gene discussed is SACK1A; the disease is neoplasm.