A Pan-Cancer Blueprint of Early Tumor Microenvironment Reprogramming

Metabolic disruption is a defining early event in tumorigenesis, yet its coordination with transcriptional and inflammatory remodeling remains unclear. Across fourteen first-stage solid tumors, we integrate transcriptomic, metabolic, immune, microRNA, and network-topological analyses to construct a blueprint of early tumor microenvironment reprogramming. Gene-network evolution revealed preferential attachment of proliferative hubs (FOXM1, CDK1, CCNB1, CDC20, TOP2A) accompanied by loss of neighborhood connectivity in key metabolic regulators (PPARA, PPARG, PRKACA/B, CREB1, SRC), indicating early erosion of lipid sensing, oxidative restraint, and metabolic-neuronal signaling. Pathway analysis demonstrated consistent suppression of fatty acid degradation and PPAR signaling, establishing a shift toward anabolic growth. ADH1B was uniformly downregulated across all cancers, linking impaired aldehyde metabolism to redox stress and inflammatory activation. Integration of inflammatory and apoptotic modules highlighted recurrent IRG-AG pairs, including IL11-MMP9-FGF10, forming a conserved inflammation-apoptosis-metabolism axis.