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

Fei Ye; Wei Huang; Yuan Xue; Erjiang Tang; Mingjie Wang; Fengchun Shi; Dong Wei; Yue Han; Peizhan Chen; Xinxin Zhang; Demin Yu

doi:10.2147/JHC.S306966

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

J Hepatocell Carcinoma. 2021 Apr 27:8:285-300. doi: 10.2147/JHC.S306966. eCollection 2021.

Authors

Fei Ye^#¹, Wei Huang^#², Yuan Xue^#³, Erjiang Tang^{4

5}, Mingjie Wang⁶, Fengchun Shi¹, Dong Wei¹, Yue Han¹, Peizhan Chen⁷, Xinxin Zhang^#¹, Demin Yu¹

Affiliations

¹ Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200025, People's Republic of China.
² Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, 226000, People's Republic of China.
³ Institute of Hepatology, The Third People's Hospital of Changzhou, Changzhou, 213000, People's Republic of China.
⁴ Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, 200090, People's Republic of China.
⁵ Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, 200090, People's Republic of China.
⁶ Department of Gastroenterology & Hepatology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 201821, People's Republic of China.
⁷ Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201821, People's Republic of China.

^# Contributed equally.

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.

Keywords: HBV‐related liver cirrhosis; ITGBL1; biomarker; chronic hepatitis B; hepatocellular carcinoma.

Grants and funding

This study was financially supported by the grants from the National Science and Technology Major Project of China (2018ZX10302205), National Natural Science Foundation of China (81572047) and Chinese foundation for hepatitis prevention and control-TianQing liver disease research fund subject (TQGB20210029), Natural Science Foundation of Shanghai (20ZR1434100), Shanghai Science and Technology Commission (19411971500).