Personalized translational medicine: Investigating YKL-40 as early biomarker for clinical risk stratification in hepatocellular carcinoma recurrence post-liver transplantation

Table 1 Mechanistic pathways linking YKL-40 to extracellular matrix remodeling and hepatocellular carcinoma recurrence

Mechanistic pathway	Role of YKL-40	Evidence	Ref.
Activation of hepatic stellate cells	Promotes activation and proliferation of hepatic stellate cells, driving liver fibrogenesis and contributing to extracellular matrix deposition	In vitro studies demonstrate direct effects on hepatic stellate cell activation	Nishimura et al[7]
TGF-β signaling pathway involvement	Regulates hepatocellular carcinoma cell proliferation, invasion, and metastasis through phosphorylation of SMAD2 and SMAD3 proteins	RNA-seq and Western blot analysis show activation of TGF-β signaling in HCC cell lines overexpressing YKL-40	Qiu et al[21]
Extracellular matrix remodeling	Enhances collagen deposition and matrix stiffening, creating a microenvironment conducive to tumor progression	Histological analysis indicates increased matrix stiffness and collagen deposition in YKL-40-rich liver tissues	Yan et al[15]
Lipid peroxide accumulation	Induces ROS and lipid accumulation, contributing to oxidative stress and tumor aggressiveness	Mouse cachectic models reveal elevated CHI3 L1 in muscle and circulation, linking lipid metabolism to HCC progression	Lu et al[20]
Macrophage activation and inflammation	Stimulates inflammatory responses, attracting macrophages to tumor sites and promoting angiogenesis and tissue remodeling	Immunofluorescence staining in NAFLD patients shows YKL-40 expression by macrophages in fibrotic liver tissue	Kumagai et al[18]

CHI3 L1: Chitinase-3-like protein 1; HCC: Hepatocellular carcinoma; LT: Liver transplantation; NAFLD: Non-alcoholic fatty liver disease; RNA-seq: Ribonucleic acid sequencing; ROS: Reactive oxygen species; TGF-β: Transforming growth factor-beta.