Identification of circulating protein markers related to tumor recurrence after liver transplantation

Abstract

BACKGROUND: Liver transplantation is an effective treatment for patients with hepatocellular carcinoma (HCC). However, higher incident of tumor recurrence is a main concern in LDLT owing to in part the severe acute phase graft injury in small-for-size graft. There is no available circulating biomarker to predict the malignancy of the recurrent liver tumor after liver transplantation. AIM: We aimed to identify potential circulating protein markers predicting tumor recurrence after liver transplantation. MATERIALS AND METHODS: A rat othotopic liver transplantation model was established using whole (100%) graft (Group W) and small-for-size (50%) graft (Group S). The recipients were injected with a rat hepatoma cell line (MH7777) via the portal vein after reperfusion. The rats were sacrificed at days 1, 3, 14 and 21 after transplantation for histological and molecular analyses. Two-dimensional electrophoresis (2-DE) was performed to compare the proteomic expression profiles of plasma samples between Group W and Group S at day 21. The identities of the differential protein spots were analyzed by mass spectrometry (MS) and further confirmed by Western blot and ELISA. RESULT: Severe acute graft injury was found in Group S at early time point after liver transplantation compared to Group W. A more progressive and invasive patterns of liver tumors were detected at day 21 in Group S compared to group W. Thirty differential protein spots were identified by comparing the 2-DE profiles of plasma samples between Group W and Group S. MS analysis revealed the identities of several potential up-regulated protein candidates in Group S including apoliprotein M, nucleoside diphosphate kinase, crystalline gamma B and D, serum amyloid P-component precursor, complement component 3, phosphoglycerate mutase 1, proteasome subunit alpha type 1 and 6, myelin basic protein, preprohaptoglobin, delta-aminolevulinic acid dehydratase, complement component factor h-like 1, aminoacylase-1A, fumarylacetoacetase and aspartate aminotransferase, and down-regulated protein candidates including plasma glutathione peroxidase precursor, complement component 1 gamma and 4. CONCLUSION: The more progressive and invasive patterns of tumor due to small-for-size graft injury can be refl ected by the changes in circulating protein expression profi les. Further evaluation of these marker candidates for the diagnosis of HCC is needed.