Serum Levels of ITGBL1 as an Early Diagnostic Biomarker for Hepatocellular Carcinoma with Hepatitis B Virus Infection.

ABSTRACT

PURPOSE: Early diagnostic biomarkers of hepatocellular carcinoma (HCC) are needed to distinguish hepatitis B virus (HBV) associated HCC (HBV-HCC) patients from at-risk patients. We assessed the diagnostic values of serum Integrin beta-like 1 (ITGBL1) for early-stage HBV-HCC. PATIENTS AND METHODS: We recruited 716 participators including 299 in the training and 417 in the validation stage, (HBV-HCC, chronic hepatitis B (CHB), HBV-related liver cirrhosis (HBV-LC), and healthy controls) between 2017 and 2020 from three centers. Serum ITGBL1 was measured by ELISA. Receiver operating characteristic (ROC) was used to calculate diagnostic accuracy. RESULTS: The serum levels of ITGBL1 in HBV-HCC patients were significantly lower than those in CHB and HBV-LC patients. This result was confirmed in the follow-up patients who progressed from HBV-LC to HCC. The optimum diagnostic cutoff value of serum ITGBL1 was 47.93ng/mL for detection of early-stage HBV-HCC. The serum ITGBL1 has higher diagnostic accuracy than AFP20 in differentiating the early-stage HBV-HCC from the at-risk patients (area under curve [AUC] 0.787 vs 0.638, p<0.05). For AFP-negative (<20ng/mL) HBV-HCC patients, serum ITGBL1 maintained diagnostic accuracy (training cohort AUC 0.756, 95% confidence interval [CI] 0.683-0.819, sensitivity 68.18%, and specificity 68.85%; validation cohort 0.744, 0.686-0.796, 81.13%, and 55.88%). Combination ITGBL1 with AFP20 significantly increased diagnostic accuracy in differentiating the HBV-HCC from at-risk patients (AUC 0.840; 0.868) than ITGBL1 (AUC 0.773, p<0.05; 0.732, p<0.0001) or AFP20 (AUC 0.705, p<0.0001; 0.773, p<0.0001) alone. CONCLUSION: The serum level of ITGBL1 improved identification of AFP-negative HBV-HCC patients, and increased diagnostic accuracy with AFP20 together in the early detection of HBV-HCC.