Project description:Background and aims: Liver transplantation (LT) is the most radical treatment for hepatocellular carcinoma (HCC) with high rates of long-term survival, but tumor recurrence after LT is an unresolved problem. The aim of our study was to identify predictive markers for tumor recurrence after liver transplantation. Methods: In a retrospective single-center study, we included all patients with LT for HCC in our institution (01/2007-12/2012). Beside demographic data, we analyzed course, bridging therapies, Serum-AFP, time point of tumor recurrence, as well as the correlation of imaging and histopathology of our recipients. Additionally, we performed a microarray analysis to identify different miRNA profiles of patients with and without HCC recurrence after LT. Single assay stem-loop real-time PCR (Q-RT-PCR) was used for validation of the results. Results: During the study period, we performed 92 LT in patients with HCC (22 women, 70 men). Twenty-two (23.9%) patients developed a recurrent HCC after LT. Our subgroup with tumor recurrence after LT, presented with a mean disease-free survival of 10 months (3-55 months) and an overall survival of 25.5 months (4-77 months). Milan criteria, AFP levels and pathologic grading had an influence on the tumor recurrence. Performing miRNA analysis, we could identify significant upregulation of 8 miRNAs and downregulation of another 5 miRNAs in patients with tumor recurrence. Consecutively, array data were successfully validated using Q-RT-PCR. Multivariate Cox regression, ROC analysis and Kaplan-Meier showed that a score consisting of two miRNAs and Milan criteria are an independent predictor for tumor recurrence-free survival. Conclusions: Despite careful selection of patients, an early recurrence of HCC after LT cannot be avoided completely. Reliable prognostic markers related to tumor biology are still missing. Analysis and validation of specific miRNAs combined with radiological parameters might lead to a promising strategy for the prediction of tumor recurrence, but prospective studies have to follow.

Project description:Background and aims: Liver transplantation (LT) is the most radical treatment for hepatocellular carcinoma (HCC) with high rates of long-term survival, but tumor recurrence after LT is an unresolved problem. The aim of our study was to identify predictive markers for tumor recurrence after liver transplantation. Methods: In a retrospective single-center study, we included all patients with LT for HCC in our institution (01/2007-12/2012). Beside demographic data, we analyzed course, bridging therapies, Serum-AFP, time point of tumor recurrence, as well as the correlation of imaging and histopathology of our recipients. Additionally, we performed a microarray analysis to identify different miRNA profiles of patients with and without HCC recurrence after LT. Single assay stem-loop real-time PCR (Q-RT-PCR) was used for validation of the results. Results: During the study period, we performed 92 LT in patients with HCC (22 women, 70 men). Twenty-two (23.9%) patients developed a recurrent HCC after LT. Our subgroup with tumor recurrence after LT, presented with a mean disease-free survival of 10 months (3-55 months) and an overall survival of 25.5 months (4-77 months). Milan criteria, AFP levels and pathologic grading had an influence on the tumor recurrence. Performing miRNA analysis, we could identify significant upregulation of 8 miRNAs and downregulation of another 5 miRNAs in patients with tumor recurrence. Consecutively, array data were successfully validated using Q-RT-PCR. Multivariate Cox regression, ROC analysis and Kaplan-Meier showed that a score consisting of two miRNAs and Milan criteria are an independent predictor for tumor recurrence-free survival. Conclusions: Despite careful selection of patients, an early recurrence of HCC after LT cannot be avoided completely. Reliable prognostic markers related to tumor biology are still missing. Analysis and validation of specific miRNAs combined with radiological parameters might lead to a promising strategy for the prediction of tumor recurrence, but prospective studies have to follow. 8 macrodissected hepatocellular carcinoma (recurrent HCC) and 10 macrodissected hepatocellular carcinoma (non-recurrent HCC).

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