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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  • Nature Reviews Gastroenterology &#38 Hepatology 01/2013; · 10.43 Impact Factor
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    ABSTRACT: AIM: It is reasonable to investigate non-tumor liver tissues to predict a risk for development of hepatocellular carcinoma (HCC). A molecular analysis of chronically damaged liver tissues may identify specific microRNA (miRNA)-expression profiles associated with a risk for multicentric (MC) HCC. METHODS: Twenty HCC patients, who underwent a curative hepatectomy were classified into two groups; a non-MC group (no MC recurrence in more than 3 years, n=10) and a MC group (MC recurrence within 3 years after hepatectomy, n=10). A miRNA microarray (955 probes) was used to compare the miRNA-expression patterns of the non-cancerous liver tissues between the two groups. This study identified the differentially expressed miRNAs related to MC recurrence in the liver remnant. RESULTS: No differences were observed between the two groups in the liver function tests and pathological variables including both tumor factors and non-tumor liver tissues. The investigation selected 20 differentially expressed miRNAs related to MC recurrence. Eighteen miRNAs were down-regulated, while 2 miRNAs were up-regulated in the MC group. A hierarchical clustering analysis identified a cluster that might be associated with risk of the MC recurrence of HCC. The MC recurrence-related miRNA included let-7d*, miR-328, and miR18a*, which potentially regulate K-ras gene expression. A significant inverse correlation between the miR-18a* expression and the K-ras mRNA expression was confirmed by quantitative reverse transcription-polymerase chain reaction. CONCLUSIONS: Specific miRNA-expression signatures in non-cancerous liver tissue may help to predict the risk for de novo development of HCC.
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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.
    Experimental and Molecular Pathology 10/2012; · 2.13 Impact Factor


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