Micro RNA Expression Profiles as Adjunctive Data to Assess the Risk of Hepatocellular Carcinoma Recurrence After Liver Transplantation

• Published in: American journal of transplantation Vol. 12; no. 2; pp. 428 - 437
• Main Authors: Barry, C. T., D'Souza, M., McCall, M., Safadjou, S., Ryan, C., Kashyap, R., Marroquin, C., Orloff, M., Almudevar, A., Godfrey, T. E.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.02.2012; Wiley
• Subjects: Biological and medical sciences; Biomarker; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Biopsy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; HCC; Humans; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - surgery; liver transplant; Liver Transplantation; Liver, biliary tract, pancreas, portal circulation, spleen; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; MicroRNAs - biosynthesis; MicroRNAs - genetics; Middle Aged; Milan criteria; miRNA; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Prognosis; Retrospective Studies; RNA, Neoplasm - genetics; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the digestive system; Tumors; Milan criteria; Relapse; Biomarker; RNA interference; Liver; Biological marker; Hepatic disease; Hepatocellular carcinoma; Risk; Homotransplantation; Profile; Liver cancer; Criterion; Surgery; Graft; miRNA; liver transplant; Digestive system; Micro RNA; HCC; Data; Malignant tumor; Gene expression; Gene silencing; Treatment; Risk factor; Digestive diseases; Cancer; Liver transplantation
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2011.03788.x

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. Micro RNA expression profiling distinguishes patients with and without hepatocellular carcinoma recurrence after liver transplant, and therefore may serve as an adjunct to current selection criteria.