Micro RNA expression profiles as adjunctive data to assess the risk of hepatocellular carcinoma recurrence after liver transplantation.

Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.
American Journal of Transplantation (Impact Factor: 6.19). 02/2012; 12(2):428-37. DOI: 10.1111/j.1600-6143.2011.03788.x
Source: PubMed

ABSTRACT Donor livers are precious resources and it is, therefore, ethically imperative that we employ optimally sensitive and specific transplant selection criteria. Current selection criteria, the Milan criteria, for liver transplant candidates with hepatocellular carcinoma (HCC) are primarily based on radiographic characteristics of the tumor. Although the Milan criteria result in reasonably high survival and low-recurrence rates, they do not assess an individual patient's tumor biology and recurrence risk. Consequently, it is difficult to predict on an individual basis the risk for recurrent disease. To address this, we employed microarray profiling of microRNA (miRNA) expression from formalin fixed paraffin embedded tissues to define a biomarker that distinguishes between patients with and without HCC recurrence after liver transplant. In our cohort of 64 patients, this biomarker outperforms the Milan criteria in that it identifies patients outside of Milan who did not have recurrent disease and patients within Milan who had recurrence. We also describe a method to account for multifocal tumors in biomarker signature discovery.

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    ABSTRACT: Organ transplantation, an accepted treatment for end stage organ failure, is often complicated by allograft rejection and disease recurrence. In this review we will discuss the potential role of microRNAs in allograft immunity especially leading to rejection of the transplanted organ. microRNAs (miRNAs), originally identified in C. elegans, are short non-coding 21-24 nucleotide sequences that bind to its complementary sequences in functional messenger RNAs and inhibits post-translational processes through RNA duplex formation resulting in gene silencing (Lau et al., 2001). Gene specific translational silencing by miRNAs regulates pathways for immune responses such as development of innate immunity, inflammation, T-cell and B-cell differentiation and signaling that are implicated in various stages of allograft rejection. miRNAs also play a role in development of post-transplant complicacies like fibrosis, cirrhosis, carcinogenesis often leading to graft loss and poor patient outcome. Recent advancements in the methods for detecting and quantifying miRNA in tissue biopsies, as well as in serum and urine samples, has led to identification of specific miRNA signatures in patients with allograft rejection and have been utilized to predict allograft status and survival. Therefore, miRNAs play a significant role in post-transplant events including allograft rejection, disease recurrence and tumor development impacting patient outcome.
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    ABSTRACT: The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise and liver transplantation (LT) represents an established curative treatment for early stage disease. As a result of organ shortage, guidelines have restricted transplantation to HCC patients with an expected 5-year post transplantation survival greater than 70 %. The Milan criteria (MC) remain a reliable and noninvasive instrument for selecting patients with 5-year survival meeting this criteria. Since the adoption of the MC by United Network for Organ Sharing (UNOS), attempts have been made to expand MC to account for the projected increase in the incidence of HCC over the next 20 years. An area of active debate focuses on identifying a subgroup of patients outside of MC with similar or better outcomes through either new expanded criteria or identifying other prognostic factors to enhance MC.
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    ABSTRACT: Liver transplantation has become an established treatment for cirrhotic patients with hepatocellular carcinoma (HCC), and the Milan criteria are now widely accepted and applied as an indication for deceased donor liver transplantation (DDLT) in Western countries. In contrast, however, due to the severe organ shortage, living donor liver transplantation (LDLT) is mainstream in Japan and in other Asian countries.
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