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

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:

• leucine aminopeptidases
• hepatocellular carcinoma
• liver transplantation
• disease-free survival
• overall survival

Abbreviations

LAPs, leucine aminopeptidases; HCC, hepatocellular carcinoma; LT, liver transplantation; AFP, alpha-fetoprotein; DFS, disease-free survival; OS, overall survival; UCSF, University of California, San Francisco; ROC curve, receiver operating characteristic curve; APN, aminopeptidase N; P-LAP, placental leucine aminopeptidase.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author Weiqiang Ju on reasonable request.

Ethics and Consent Statement

The study was approved by the medical ethic committee of the First Affiliated Hospital, Sun Yat-sen University, and due to the retrospective nature of the study, written informed consent was waived.

Consent for Publication

Written informed consent for publication was obtained.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to declare.