Is metabolic dysfunction-associated steatotic liver disease truly irrelevant? Unmasking the heterogeneity and confounders in pancreatic cancer outcomes

Figure 1 Biological mechanisms of pancreatic cancer metastasis. A: In the inflammatory milieu, hepatic neutrophils undergo NETosis, expelling DNA webs decorated with granular proteins. These structures physically entrap circulating pancreatic cancer cells, acting as an initial scaffold for metastatic seeding; B: Activated hepatic stellate cells transdifferentiate to deposit a stiff extracellular matrix composed of collagen and fibronectin fibers. This rigid architecture facilitates cancer cell adhesion via integrin signaling and promotes survival; C: Lipid-engorged hepatocytes release exogenous fatty acids, which are actively taken up by cancer cells to fuel mitochondrial β-oxidation and support rapid biomass production; D: Tumor-associated macrophages adopt a protective phenotype, shielding the tumor from cytotoxic T-cells. Meanwhile, metabolically stressed senescent hepatocytes release senescence-associated secretory phenotype factors, which stimulate tumor proliferation in a paracrine manner.