Mechanisms
A four-protein urinary panel including CETP, combined with tumor diameter and AFP/GGT levels, predicts microvascular invasion in liver cancer with concordance indices up to 0.809 (BMC Med 2023)
Original title: Noninvasive urinary protein signatures combined clinical information associated with microvascular invasion risk in HCC patients
Microvascular invasion (MVI) is the main prognostic factor in hepatocellular carcinoma (HCC). The authors conducted label-free quantitative proteomic studies on urine from 91 HCC patients and 22 healthy controls to identify preoperative biomarkers predicting MVI status. Urinary proteomic features of healthy controls reflected active metabolic processes, while the HCC group showed pathways related to cell adhesion and proliferation, including extracellular matrix organization and cell-cell junction organization. Using expression levels of four urinary proteins, cholesteryl ester transfer protein (CETP), HGFL, L1CAM and LAIR2, combined with tumor diameter, serum AFP and GGT concentrations, the authors built a preoperative nomogram predicting MVI status, achieving concordance indexes of 0.809 in the training cohort and 0.783 in an independent testing cohort (n=23), confirmed by ELISA in a further validation cohort (n=57).
Original abstract
Background: Microvascular invasion (MVI) is the main factor affecting the prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify accurate diagnostic biomarkers from urinary protein signatures for preoperative prediction.
Methods: We conducted label-free quantitative proteomic studies on urine samples of 91 HCC patients and 22 healthy controls. We identified candidate biomarkers capable of predicting MVI status and combined them with patient clinical information to perform a preoperative nomogram for predicting MVI status in the training cohort. Then, the nomogram was validated in the testing cohort (n = 23). Expression levels of biomarkers were further confirmed by enzyme-linked immunosorbent assay (ELISA) in an independent validation HCC cohort (n = 57).
Results: Urinary proteomic features of healthy controls are mainly characterized by active metabolic processes. Cell adhesion and cell proliferation-related pathways were highly defined in the HCC group, such as extracellular matrix organization, cell-cell adhesion, and cell-cell junction organization, which confirms the malignant phenotype of HCC patients. Based on the expression levels of four proteins: CETP, HGFL, L1CAM, and LAIR2, combined with tumor diameter, serum AFP, and GGT concentrations to establish a preoperative MVI status prediction model for HCC patients. The nomogram achieved good concordance indexes of 0.809 and 0.783 in predicting MVI in the training and testing cohorts.
Conclusions: The four-protein-related nomogram in urine samples is a promising preoperative prediction model for the MVI status of HCC patients. Using the model, the risk for an individual patient to harbor MVI can be determined.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.