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High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection.

ABSTRACT: Hepatocellular 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.In 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.Ten 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.We 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.

SUBMITTER: von Felden J

PROVIDER: S-EPMC5242004 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection.

von Felden Johann J Heim Denise D Schulze Kornelius K Krech Till T Ewald Florian F Nashan Björn B Lohse Ansgar W AW Wege Henning H

BMC cancer 20170118 1

<h4>Background</h4>Hepatocellular 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.<h4>Methods</h4>In 52 patients u ...[more]

PMID: 28100188

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Project description:BackgroundEarly recurrence of hepatocellular carcinoma (HCC) is a major obstacle to improving the prognosis, and no widely accepted adjuvant therapy guideline for patients post-liver resection is available. Currently, all available methods and biomarkers are insufficient to accurately predict post-operation HCC patients' risk of early recurrence and their response to adjuvant therapy.MethodsIn this study, we downloaded four gene expression datasets (GSE14520, GSE54236, GSE87630, and GSE109211) from the Gene Expression Omnibus database and identified 34 common differentially expressed genes associated with HCC dysregulation and response to adjuvant sorafenib. Then, we constructed a novel 11-messenger RNA predictive model by using ROC curves analysis, univariate Cox regression analysis, and LASSO Cox regression analysis. Furthermore, we validated the predictive values of the risk model in GSE14520 and TCGA-LIHC cohorts by using Kaplan-Meier survival analysis, multivariable Cox regression analysis, and decision curve analysis, respectively.ResultsThe risk score model could identify patients with a high risk of HCC recurrence at the early stage and could predict the response of patients to adjuvant sorafenib. Patients with a high risk score had a worse recurrence rate in training cohorts (2-year: p < 0.0001, hazard ratio (HR): 4.658, confidence interval 95% CI [2.895-7.495]; 5-year: p < 0.0001, HR: 3.251, 95% CI [2.155-4.904]) and external validation cohorts (2-year: p < 0.001, HR: 3.65, 95% CI [2.001-6.658]; 5-year: p < 0.001, HR: 3.156, 95% CI [1.78-5.596]). The AUC values of the risk score model for predicting tumor early recurrence were 0.746 and 0.618, and that of the risk score model for predicting the response to adjuvant sorafenib were 0.722 and 0.708 in the different cohort, respectively. Multivariable Cox regression analysis and decision curve analysis also showed that the risk score model was superior to and independent of other clinicopathologic characteristics. Moreover, the risk score model had excellent abilities to predict the overall survival and HCC recurrence of patients with the same tumor stage category.ConclusionsOur risk model is a reliable and superior predictive tool. With this model, we could optimize the risk stratification based on early tumor recurrence and could evaluate the response of patients to adjuvant sorafenib after liver resection.

Dataset Information

High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection.

Publications

High expression of micro RNA-135A in hepatocellular carcinoma is associated with recurrence within 12 months after resection.

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