Abstract
ObjectiveHepatocellular 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.MethodsWe 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).ResultsThe 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’.ConclusionmicroRNA profiling can predict HCC recurrence in Milan criteria cases.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and is the fourth most common cause of mortality [1,2]
The impaired liver function caused by liver cirrhosis often restricts treatment options, even for early HCC
There has been an intense debate about which treatment option of Liver resection (LR) or orthotopic liver transplantation (OLT) is the optimal initial treatment for HCC patients with no to mild liver cirrhosis (Child-Pugh A/B)
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and is the fourth most common cause of mortality [1,2]. The impaired liver function caused by liver cirrhosis often restricts treatment options, even for early HCC. For HCC patients with severe liver cirrhosis (Child-Pugh C), OLT is considered the first-line treatment. In these cases, LR is contraindicated because of impaired liver function. The strategy of a primary LR and salvage transplantation for intrahepatic HCC recurrence is a reasonable tactic for early resectable HCC with preserved liver function. In this strategy, it is important to predict recurrent tumors for selecting the follow-up protocol of patients after LR
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