Development of Innovative Diagnostic Procedures for Post-Liver Transplant Patients: At-Home Health Screening by Detection of Nuclear Antigen Release and Following Molecular Diagnosis for Precision Medicine

Liver transplantation is an effective therapy for end-stage liver diseases and the outcomes are dependent on the precise prediction/diagnosis of post-transplant complications for early and appropriate treatments. The incidence of acute rejection (AR) or post-transplant hepatocellular carcinoma (HCC) recurrence is approximately 15% in our institute. Therefore, the discovery of biomarkers for early prediction and precise diagnosis of post-transplant complications remains an important issue. In our previous studies, we have demonstrated that levels of circulating nuclear antigens such as histone H1 and high-mobility group box 1 (HMGB1) were dramatically elevated during AR in the lethal AR combination. The mild AR combination or other inflammation models such as acute hepatitis and allergic rhinitis revealed a lower level of circulating nuclear antigens. Therefore, the measurement of circulating nuclear antigens may provide an understanding into the intensity of inflammatory responses and may be suitable for at-home health screening. In addition, we have demonstrated AR-specific elevation of hepatic miR-301a and Th17 cell-mediated systemic inflammation in the lethal AR combination. Recently, we have demonstrated the elevation of circulating exosomal miR-92b in patients with post-transplant HCC recurrence. These molecular biomarkers could be applied into the diagnosis of AR and HCC recurrence. In this project, we will use immunochromatography for quick and easy detection of nuclear antigen release as an effective screening method for abnormal inflammatory responses in experimental and clinical liver transplantation (1st to 2nd year). For molecular diagnosis of AR, we will perform in situ hybridization with specific probe for miR-301a after pathological evaluation of AR in liver allografts as well as the characterization of AR-specific circulating exosomal microRNAs (1st to 2nd year). We will also explore the expression profiles of target microRNAs published/discovered by our group and others to develop circulating exosomal microRNA panels to predict AR and HCC recurrence (1st to 3rd year). We expect to gather supportive evidences for the development of innovative diagnostic procedures such as at-home health screening and molecular diagnosis for precision medicine.

Project ID:PC10908-0305
External Project ID:MOST109-2320-B182-014