Role of leukemia inhibitory factor in predicting recurrence of hepatocellular carcinoma in recipients undergoing liver transplantation

Abstract

Objective To investigate the role of leukemia inhibitory factor (LIF) in predicting the recurrence of hepatocellular carcinoma (HCC) in the recipients undergoing liver transplantation. Methods Clinical data of 105 HCC recipients undergoing liver transplantation in the First Affiliated Hospital of Zhejiang University from August 2009 to December 2015 were retrospectively analyzed. The informed consents of all patients and their family were obtained and the local ethical committee approval was received. Among the recipients, 100 were male and 5 female, aged (50±8) years on average. 43 patients were diagnosed with moderately-well or moderately-differentiated HCC and 62 cases of lowly-differentiated HCC. 22 patients met the Milan criteria. The LIF expression was detected by immunohistochemical tissue microarray and were statistically compared between HCC and para-cancerous tissues by t test. The model of predicting HCC recurrence after liver transplantation was established by Cox multivariate regression. The predictive value of the model was assessed by ROC curve and DeLong test. Survival analysis was performed by Kaplan-Meier method and Log-rank test. Results The LIF expression intensity in HCC tissues was 7.3±2.6, significantly higher than 5.0±2.4 in the para-cancerous tissues (t=6.670, P<0.05). Cox multivariate regression analysis indicated that LIF expression in HCC tissues, lnAFP and vascular invasion were the independent risk factors for HCC recurrence of the patients after liver transplantation (HR=1.178, 1.177, 2.280; P<0.05). A recurrence prediction model was established: 0.164×LIF expression level + 0.163×lnAFP + 0.824×vascular invasion. According to this model, all the recipients were divided into the low-risk and high-risk groups. The 1-, 3-, 5-year survival rates in low-risk group were 82.7%, 77.7%, 73.6%, significantly higher compared with 30.2%, 17.3%, 17.3% in high-risk group, respectively (χ2=36.890, P<0.05). The area under ROC curve of this model for predicting HCC recurrence in patients undergoing liver transplantation was 0.849, significantly better than 0.626 of the Milan criteria (Z=3.638, P<0.05). Conclusions LIF expression is up-regulated in HCC tissues. LIF expression is an independent risk factor for HCC recurrence in patients after liver transplantation. The corresponding model can tell patients with high-risk recurrence from those with low-risk recurrence. Compared with the Milan criteria, it can better predict HCC recurrence after liver transplantation. Key words: Carcinoma, hepatocellular; Liver transplantation; Leukemia inhibitory factor; Recurrence; Prognosis