Citrullinated matrisome: An emerging stromal determinant in hepatocellular carcinoma prognostication

Figure 1 Conceptual framework of the citrullinated matrisome in hepatocellular carcinoma progression. Chronic liver injury activates hepatic stellate cells (HSCs), which upregulate glial fibrillary acidic protein (GFAP). Peptidylarginine deiminases (PADs), particularly PAD2, citrullinate GFAP and other extracellular matrix (ECM) proteins, generating the “citrullinated matrisome”. This leads to ECM remodeling, altered integrin signaling, and recruitment of regulatory T cells (Tregs) and myeloid-derived suppressor cells, ultimately promoting HCC progression, metastasis, and poor prognosis. HBV: Hepatitis B virus; HCV: Hepatitis C virus; MASLD: Metabolic dysfunction-associated steatotic liver disease; HSC: Hepatic stellate cell; α-SMA: Alpha-smooth muscle actin; GFAP: Glial fibrillary acidic protein; PAD: Peptidylarginine deiminase; ECM: Extracellular matrix; cit-GFAP: Citrullinated glial fibrillary acidic protein; HCC: Hepatocellular carcinoma.