Noninvasive urinary protein signatures combined clinical information associated with microvascular invasion risk in HCC patients

Abstract

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.

Keywords

• Hepatocellular carcinoma (HCC)
• Microvascular invasion (MVI)
• Urine proteomics
• Biomarker diagnosis