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MicroRNA profile predicts recurrence after resection in patients with hepatocellular carcinoma within the Milan Criteria.

ABSTRACT: OBJECTIVE: Hepatocellular carcinoma (HCC) is difficult to manage due to the high frequency of post-surgical recurrence. Early detection of the HCC recurrence after liver resection is important in making further therapeutic options, such as salvage liver transplantation. In this study, we utilized microRNA expression profiling to assess the risk of HCC recurrence after liver resection. METHODS: We examined microRNA expression profiling in paired tumor and non-tumor liver tissues from 73 HCC patients who satisfied the Milan Criteria. We constructed prediction models of recurrence-free survival using the Cox proportional hazard model and principal component analysis. The prediction efficiency was assessed by the leave-one-out cross-validation method, and the time-averaged area under the ROC curve (ta-AUROC). RESULTS: The univariate Cox analysis identified 13 and 56 recurrence-related microRNAs in the tumor and non-tumor tissues, such as miR-96. The number of recurrence-related microRNAs was significantly larger in the non-tumor-derived microRNAs (N-miRs) than in the tumor-derived microRNAs (T-miRs, P<0.0001). The best ta-AUROC using the whole dataset, T-miRs, N-miRs, and clinicopathological dataset were 0.8281, 0.7530, 0.7152, and 0.6835, respectively. The recurrence-free survival curve of the low-risk group stratified by the best model was significantly better than that of the high-risk group (Log-rank: P?=?0.00029). The T-miRs tend to predict early recurrence better than late recurrence, whereas N-miRs tend to predict late recurrence better (P<0.0001). This finding supports the concept of early recurrence by the dissemination of primary tumor cells and multicentric late recurrence by the 'field effect'. CONCLUSION: MicroRNA profiling can predict HCC recurrence in Milan criteria cases.

SUBMITTER: Sato F

PROVIDER: S-EPMC3029327 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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MicroRNA profile predicts recurrence after resection in patients with hepatocellular carcinoma within the Milan Criteria.

Sato Fumiaki F Hatano Etsuro E Kitamura Koji K Myomoto Akira A Fujiwara Takeshi T Takizawa Satoko S Tsuchiya Soken S Tsujimoto Gozoh G Uemoto Shinji S Shimizu Kazuharu K

PloS one 20110127 1

<h4>Objective</h4>Hepatocellular carcinoma (HCC) is difficult to manage due to the high frequency of post-surgical recurrence. Early detection of the HCC recurrence after liver resection is important in making further therapeutic options, such as salvage liver transplantation. In this study, we utilized microRNA expression profiling to assess the risk of HCC recurrence after liver resection.<h4>Methods</h4>We examined microRNA expression profiling in paired tumor and non-tumor liver tissues from ...[more]

PMID: 21298008

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Project description:ObjectivesTo assess survival after liver resection and transplantation in patients with hepatocellular carcinoma (HCC) beyond Milan criteria.BackgroundThe role of liver resection and transplantation remains controversial for patients with HCC beyond Milan criteria. Resection of advanced tumors and transplantation using extended-criteria are pursued at select high-volume center.MethodsPatients from 5 liver cancer centers in the United States who had liver resection or transplantation for HCC beyond Milan criteria between 1990 and 2011 were included in the study. Multivariable and propensity-matching analyses estimated the effects of clinical factors and operative selection on survival.ResultsOf 608 patients beyond Milan without vascular invasion, 480 (79%) patients underwent resection and 128 (21%) underwent transplantation. Clinicopathologic profiles between resection and transplant patients differed significantly. Hepatitis C and cirrhosis were more prevalent in transplantation group (P < 0.001). Resection patients had larger tumors [median 9 cm, interquartile range (IQR): 6.5-12.9 cm vs. median 4.1, IQR: 3.4-5.3 cm, P < 0.001]; transplant patients were more likely to have multiple tumors (78% vs 28%, P < 0.001).Overall (OS) and disease-free survival (DFS) were both greater after tumor downstaging and transplantation than resection (all P < 0.001). OS did not differ between liver transplant recipients who were not pretreated or pretreated and failed to downstage compared with propensity-matched liver resection patients (P ≥ 0.176); DFS in this propensity matched cohort was greater after liver transplantation (P ≤ 0.017).ConclusionsLiver resection and transplantation provide curative options for patients with HCC beyond Milan criteria. Further treatment strategies aimed at the efficiency and durability of tumor downstaging and expansion of the role of transplantation among suitable candidates could improve outcomes in patients with large or multifocal HCC.

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MicroRNA profile predicts recurrence after resection in patients with hepatocellular carcinoma within the Milan Criteria.

Publications

MicroRNA profile predicts recurrence after resection in patients with hepatocellular carcinoma within the Milan Criteria.

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