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: 5.68). 02/2012; 12(2):428-37. DOI: 10.1111/j.1600-6143.2011.03788.x
Source: PubMed


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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Available from: Mary D'Souza, Jul 30, 2014
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    • "A French group also proposed that the prediction of HCC recurrence after LT is significantly improved by applying modified Milan criteria that incorporate the AFP level [21]. Recently, micro-RNA clusters were extensively investigated as a biomarker representing the biologic behavior of HCC [35, 36] in association with recurrence. "
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    ABSTRACT: Background 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. Summary Unlike DDLT, LDLT is not limited by the restrictions imposed by the nationwide allocation system, and the indication for LDLT in patients with HCC often depends on institutional or case-by-case considerations, balancing the burden on the donor, the operative risk, and the overall survival benefit for the recipient. Accumulating data from a nationwide survey as well as individual center experience indicate that extending the Milan criteria is warranted. Key Messages While the promotion of DDLT should be intensified in Japan and other Asian countries, LDLT will continue to be a mainstay for the treatment of HCC in cirrhotic patients.
    Full-text · Article · May 2014
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    • "Altered expression of certain miRNAs in the cancerous liver has been linked to an increased risk of disease recurrence following resection. Specifically, three studies defined miRNA expression signatures, consisting of 7, 18 and 67 miRNAs, respectively , from HCC tissue samples to distinguish patients with a high risk of recurrence from those with a low risk (Chung et al., 2010; Barry et al., 2012; Han et al., 2012). From these studies miRs- 10b, 21, 34c, 155 and let-7d positively correlated with recurrence, whilst miRs-15b, 20a, 24, 122, 145 and 182 negatively correlated with recurrence. "
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    ABSTRACT: Since their discovery more than a decade ago microRNAs have been demonstrated to have profound effects on almost every aspect of biology. Numerous studies in recent years have shown that microRNAs have important roles in development and in the etiology and progression of disease. This review is focused on microRNAs and the roles they play in liver development, regeneration and liver disease; particularly chronic liver diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, viral hepatitis and primary liver cancer. The key microRNAs identified in liver development and chronic liver disease will be discussed together with, where possible, the target messenger RNAs that these microRNAs regulate to profoundly alter these processes.
    Full-text · Article · Apr 2014 · The international journal of biochemistry & cell biology
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    • "In recent years, studies have shown that miRNAs are deregulated under different pathological conditions, such as cancer and liver injury. MiRNA expression profiles have also been reported for distinguishing cancerous from non-cancerous tissue for finding biomarkers or therapeutic targets [17,18]. MiRNA might also be an important factor in the complex interaction between parasites and their hosts, as well as in parasite drug resistance [19,20,21]. "
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    ABSTRACT: The reed vole Microtus fortis is the only mammal known in China in which the growth, development and maturation of schistosomes (Schistosoma japonicum) is prevented. It might be that the anti-schistosomiasis mechanisms of M. fortis associate with microRNA-mediated gene expression, given that the latter has been found to be involved in gene regulation in eukaryotes. In the present study, the difference between pathological changes in tissues of M. fortis and of mice (Mus musculus) post-schistosome infection were observed by using hematoxylin-eosin staining. In addition, microarray technique was applied to identify differentially expressed miRNAs in the same tissues before and post-infection to analyze the potential roles of miRNAs in schistosome infection in these two different types of host. Histological analyses showed that S. japonicum infection in M. fortis resulted in a more intensive inflammatory response and pathological change than in mice. The microarray analysis revealed that 162 miRNAs were expressed in both species, with 12 in liver, 32 in spleen and 34 in lung being differentially expressed in M. fortis. The functions of the differentially expressed miRNAs were mainly revolved in nutrient metabolism, immune regulation, etc. Further analysis revealed that important signaling pathways were triggered after infection by S. japonicum in M. fortis but not in the mice. These results provide new insights into the general mechanisms of regulation in the non-permissive schistosome host M. fortis that exploits potential miRNA regulatory networks. Such information will help improve current understanding of schistosome development and host-parasite interactions.
    Full-text · Article · Dec 2013 · PLoS ONE
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