Characterization of a hepatocellular carcinoma risk genotype serving as a predictor of recurrence after living donor liver transplantation and its relation to the modulated host milieu observed in the regeneration liver graft

• Antragsteller: Privatdozent Dr. Frank Weber
• Fachliche Zuordnung: Allgemein- und Viszeralchirurgie
• Förderung: Förderung von 2007 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5397027

Recurrence is a major problem after living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC), particularly in tumors exceeding the classic Milan criteria. Standard selection based on imaging results misinterprets the tumor stage in up to 30% of cases. In addition, due to a lack of "biological selection" while on the regular waiting list for transplantation, HCC candidates for LDLT might be at particular risk of incorrect selection. There is an obvious need for identification of a molecular signature of HCC that may serve as an additional marker for prediction of disease recurrence. In addition, LDLT recipients represent unique situation since the transplanted liver graft likely stimulates an array of cytokines and growth hormones not only related to regeneration but also to carcinogenesis. Therefore, we utilize a genome-wide gene expression analysis that will allow us to identify a molecular signature defining a risk-genotype of HCC related to early intrahepatic recurrence after LDLT. To this end, a pilot study allowed us to begin to understand the potential molecular pathways involved in HCC recurrence. These signatures, predictive of HCC recurrence, will be retrospectively validated and prospectively assessed and correlated with clinical outcome. Furthermore, we will assess the LDLT recipient for cytokine and growth hormone changes that are a result of the regenerating liver graft and that might be relevant for HCC recurrence. Finally, we will test those HCC with defined risk-genotype and investigate their oncogenic properties under modulated local milieu by orthotopic transplantation in established animal models. Based on previous observations we will focus here on the role of the hypoxia-induced factors and the Toll-Like Receptor pathways.

• DFG-Verfahren: Klinische Forschungsgruppen
• Teilprojekt zu: KFO 117: Optimierung der Leberlebendspende
• Beteiligte Personen: Professor Dr. Maximilian Bockhorn; Professor Dr. Joachim Fandrey; Professorin Dr. Andrea Frilling