The prognostic value of combined analysis of KLF4 expression and the Milan criteria in hepatocellular carcinoma patients after orthotopic liver transplantation

Abstract

Objective To evaluate the prognostic value of combined analysis of the biomarker Kruppel-like factor 4 (KLF4) and the Milan criteria in hepatocellular carcinoma (HCC) patients treated by orthotopic liver transplantation (OLT).Method The clinicopathological data and outcome of the recruited 105 HCC patients undergoing OLT from October 2001 to April 2009 were retrospectively analyzed.KLF4 expression in HCC and paired non-tumor tissue was detected by immonohistochemistry and confirmed by Western blotting analysis.Five-year overall survival (OS) and recurrence-free survival (RFS) rate and survival curves of the grouped patients were calculated and plotted by Kaplan-Meier method.Result The level of KLF4 expression was lower in HCC than that in paired non-tumor tissue (P＜0.05).KLF4 expression was significantly lower in poorly differentiated HCC than that in well-moderately differentiated HCC (P =0.008).Loss of KLF4 was an independent risk factor for predicting tumor recurrence and survival of HCC after OLT (HR =0.459 and 5.42,respectively,P＜0.001).The level of KLF4 expression could not differentiate the OS and RFS rate in the patients with tumors meeting the Milan criteria,whereas the OS and RFS rate in the patients with tumors exceeding the Milan criteria differentiated according to KLF4 expression.The patients with tumors beyond the Milan criteria and exhibiting moderate to high KLF4 expression had unexpectedly favorable 5-year OS (91.7％) and RFS (70.5％) rate.Conclusion KLF4 is a useful biomarker for prognostication of HCC patients undergoing OLT.Integrated use of KLF4 biomarker and the Milan criteria improves accurate prediction of survival and tumor recurrence for HCC patients after OLT. Key words: Carcinoma, hepatocellular; Liver transplantation; KLF4; Prognosis