Prognostic Value of Preoperative Serum Leucine Aminopeptidases in Hepatocellular Carcinoma Patients Who Underwent Liver Transplantation

Cancer Manag Res. 2021 Feb 5:13:1053-1066. doi: 10.2147/CMAR.S292128. eCollection 2021.

Abstract

Background: Leucine aminopeptidases (LAPs) have been reported to be involved in tumor cell proliferation, invasion and angiogenesis. However, the relationship between serum leucine aminopeptidases and prognosis of hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) was not yet reported. We aimed to evaluate the prognostic value of preoperative serum leucine aminopeptidases in these patients.

Methods: Clinical data of 106 HCC patients who underwent LT were retrospectively analyzed. The sex ratio, age, HBV infection, Child-Pugh stage, preoperative tumor therapy, AFP, the largest tumor size, tumor number, Edmondson grading, macro- and micro-vascular invasion of patients with different serum LAP level and compositions of patients who met the criteria of Milan, UCSF or Hangzhou were compared using the chi-square test. The Kaplan-Meier method was performed in survival analysis and the log rank test was used in survival comparison.

Results: Serum LAPs were correlated with alpha-fetoprotein (AFP), the largest tumor size, tumor number and macro-vascular invasion. Patients with serum LAPs > 87 U/L showed significantly poorer disease-free survival (DFS) and overall survival (OS) than those with serum LAPs ≤ 87 U/L. Univariate analysis indicated that serum LAPs, AFP, the largest tumor size, tumor number, and macro- and micro-vascular invasion were all associated with DFS and OS. Multivariate analysis showed that serum LAPs, macro-vascular invasion and the largest tumor size were independently correlated with DFS and OS. Serum LAPs could also distinguish prognosis between patients with different status of AFP, the largest tumor size, tumor number, and macro- and micro-vascular invasion, as well as patients within and beyond selection criteria, such as Milan, University of California, San Francisco and Hangzhou criteria.

Conclusion: Elevated preoperative serum LAPs were associated with advanced tumor stage and aggressive biological behavior, and thus a poor outcome, which could be a prognostic marker for HCC patients who underwent LT.

Keywords: disease-free survival; hepatocellular carcinoma; leucine aminopeptidases; liver transplantation; overall survival.

Grants and funding

This study was supported by the Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (2013A061401007), the Guangdong Provincial international Cooperation Base of Science and Technology (Organ Transplantation) (2015B050501002), the Science and Technology Planning Project of Guangzhou City (201605131229503), the Science and Technology Planning Project of Guangdong Province (2013B040200019), the Special Foundation for Science and Technology Development of Guangdong Province (2017B090904010), the Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20190809095801653, JCYJ20190809100217290), the Sanming Project of Medicine in Shenzhen (SZSM201612021) and the Scientific Research Project of Health and Family Planning Commission of Shenzhen Municipality (SZXJ2018086).