Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma.

Wei RR, Huang GL, Zhang MY, Li BK, Zhang HZ, Shi M, Chen XQ, Huang L, Zhou QM, Jia WH, Zheng XF, Yuan YF, Wang HY.

Source

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center.

Abstract

PURPOSE:

MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma (HCC) and delineate their clinical significance for HCC.

EXPERIMENTAL DESIGN:

HCC patients undergoing hepatectomy were randomly divided into training set (60 patients) and test set (50 patients). Another 56 patients were used as an independent cohort. The miRNA expression levels were detected by microarray and verified by qRT-PCR.

RESULTS:

A 30-miRNA signature consisting of 10 down-regulated and 20 up-regulated miRNAs was established for distinguishing HCC from non-cancerous liver tissues in the training set with 99.2% accuracy. The classification accuracies of this signature were 97% and 90% in the test set and independent cohort, respectively. The expression level of 4 miRNAs in the 30-miRNA signature was verified by real-time RT-PCR in the training set. Twenty miRNAs were then selected to construct prognostic signature in the training set. Of the 20 miRNAs, 6 were risk factors and 14 were protective factors. A formula based on the 20 miRNAs was built to compute prognostic index. Kaplan-Meier analysis showed that patients with a higher prognostic index had a significantly lower survival than those with a low index. This was verified in the test and independent sets. Multivariate analysis indicated that the 20-miRNA signature was an independent prognostic predictor.

CONCLUSIONS:

The 30- and 20-miRNA signatures identified in this study should provide new molecular approaches for diagnosis and prognosis of HCC patients and clues for elucidating molecular mechanism of hepatocarcinogenesis.