Up-regulation of miR-9 expression predicate advanced clinicopathological features and poor prognosis in patients with hepatocellular carcinoma

Abstract

Background: MicroRNAs (miRNAs) are endogenous small (19-24 nt long) noncoding RNAs that regulate gene expression in a sequence specific manner. An increasing association between miRNA and cancer has been recently reported. Hepatocellular carcinoma (HCC), as the fifth most common cancer and the most common cause of death in men, has become the third leading cause of cancer-related deaths globally. In this study, we investigated the miR-9 expression in HCC to evaluate their value in prognosis of this tumor.

Methods: The expression of miR-9 in matched normal and tumor tissues of HCC was evaluated using a quantitative real-time RT-PCR. A Kaplan-Meier survival curve was generated following a log-rank test.

Results: It was observed that miR-9 expression was upregulated in HCC tissues compared with noncancerous liver tissues (7.26 ± 1.30 vs. 3.14 ± 1.08, P < 0.001). The up-regulation of miR-9 in HCC cancer tissues was also significantly correlated with aggressive clinicopathological features. We found that the patients with high miR-9 expression have a higher tumor staging (P = 0.0389) and are in higher risk of venous infiltration (P < 0.0001). Moreover, the results of Kaplan-Meier analyses showed that HCC patients with the high miR-9 expression tend to have shorter overall survival (P < 0.0001). The multivariate analysis clearly indicated that the high miR-9 expression in biopsy samples may be considered as an independent prognostic factor in HCC for decreased survival (4.28; 95%CI, 2.77-7.23, P < 0.001).

Conclusion: Our data indicate the potential of miR-9 as a novel prognostic biomarker for HCC. Large well-designed studies with diverse populations and functional evaluations are warranted to confirm and extend our findings.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_228.

Figure 1

Tumor differentiation according to the Edmondson grading system. Poor differentiation (a); Moderate (b); and Well (c).

Figure 2

miR-9 expression in 200 pairs of HCC and adjacent non-neoplatic liver tissues detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. (a) Comparison between all the HCC tissues and non-neoplastic tissues. (b) Comparison between early stage HCC tissues and non-neoplastic tissues. (c) Comparison between advantaged stage HCC tissues and non-neoplastic tissues. (d) Comparison between early and advantaged stage HCC tissues.

Figure 3

Kaplan-Meier survival curves for HCC patients with high or low expression of miR-9. (a) The 5-year overall survival rate of all 200 HCC patients with high or low miR-9 expression; (b) The 5-year overall survival rate of 71 HCC patients with early stage in high or low miR-9 expression group; (c) The 5-year overall survival rate of 129 HCC patients with advanced stage in high or low miR-9 expression group.