Abstract
BackgroundHepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection. Early recurrence is driven by synchronous microscopic intrahepatic metastases. The predictive value of histological parameters is discussed controversially and adjuvant therapy is not established. The aim of this study was to identify patients at high risk for early intrahepatic recurrence by expression profiling of selected micro RNAs.MethodsIn 52 patients undergoing HCC resection between 2011 and 2014, liver and tumor tissue was collected during surgery. Twelve patients with incomplete data regarding HCC recurrence, secondary liver transplantation, or perioperative death were excluded, leaving 40 patients with early recurrence <12 months (R+) or without recurrence for >24 months (R-) to compare grading, T, L, V, and R status. If tissue quality permitted, micro RNAs were measured in HCC and liver tissue.ResultsTen women and 30 men (64.0 ± 10.2 years) were analyzed. R+ occurred in 29 patients 6.2 ± 4.5 months after resection. Surveillance of R- was 26.2 ± 5.2 months. High intratumoral expression of miR-135a was associated with high risk of recurrence (HR = 4.2, p = 0.024, time to recurrence 8.8 ± 2.0 vs. 24.8 ± 4.4 months in patients with low miR-135a expression). As expected, T3 status was correlated with early recurrence, while other histological parameters and expression of miR-21, miR-122, and miR-125a did not.ConclusionsWe show a significant association between high expression of miR-135a and early HCC recurrence. Therefore, high intratumoral miR-135a expression might serve as a novel biomarker to identify patients urgently requiring adjuvant therapy post resection.
Highlights
Hepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection
The passenger Micro RNAs (miRNAs) is typically degraded, while the guiding miRNA strand is incorporated into the Ribonucleic acid (RNA)-induced silencing complex (RISC) to mediate messenger RNA degradation or translational inhibition depending on the base pairing between miRNA and target mRNA [7, 8]
Patient characteristics Twelve of 52 patients were excluded from our analysis because of incomplete data regarding Hepatocellular carcinoma (HCC) recurrence, secondary liver transplantation, or death within 30 days after operation, leaving 40 patients for further investigation
Summary
Hepatocellular carcinoma has a dismal prognosis due to recurrence rates of up to 70% after curative resection. The aim of this study was to identify patients at high risk for early intrahepatic recurrence by expression profiling of selected micro RNAs. Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in men and the third most frequent cause of cancer death worldwide [1]. Micro RNA 122 (miR-122) is liver specific and plays a role in hepatocyte differentiation, viral hepatitis, and HCC development as a tumor suppressor. Micro RNA 125b (miR-125b) acts primarily as a tumor suppressor in HCC by targeting Bcl-2 and inducing cancer cell apoptosis [17]. It inhibits cell migration and invasion by targeting LIN28B, and has recently been connected to epithelialmesenchymal transition in HCC [18, 19]. Two other studies showed that miR-135a down-regulates Krüppel-like factor 4, up-regulates the expression of matrix metalloproteinase-2 and Akt, and down-regulates forkhead box O1, resulting in higher proliferation and invasiveness of HCC cells [21, 22]
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