Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the liver. Since postoperative recurrence and intrahepatic metastases occur frequently, the postoperative 5-year survival rate is low. To investigate the molecular mechanisms of HCC progression, mRNA as well as microRNA (miRNA) expression levels have been profiled in various studies. However, no previous study has comprehensively compared the expression of miRNAs in HCC patients with various clinical features using the tumor and surrounding non-tumor tissues and normal liver samples. In this study, we profiled the expression of miRNAs in tumor and non-tumor tissues from 40 HCC patients with heterogeneous pathogenesis and 6 surrounding non-tumor tissues from patients with metastatic liver cancer. To identify miRNAs specific to each disease state, we comprehensively compared the expression of miRNAs in various combinations. The results indicate that the expression of many known as well as novel miRNAs was altered in patients with the hepatitis C virus infection compared with those with the hepatitis B virus and without any virus infection. The following miRNAs were downregulated in the tumor and non-tumor tissues, and thus could serve as novel biomarkers for chronic liver diseases: miR-18b*, miR-296-5p, miR-557, miR-581, miR-625*, miR-1228, miR-1249 and miR-2116*. Similarly, miR-129*, miR-146b-3p and miR-448 are novel candidates for HCC biomarkers regardless of virus infection.

Figure 1.

Representative miRNAs detected in pairwise comparisons between tumor and non-tumor tissues. The upward and downward arrows indicate up- and downregulation, respectively, of miRNA in the tumor tissues.

Figure 2.

Representative miRNAs detected in comparisons of the normal liver samples with non-tumor tissues. The upward and downward arrows indicate up- and downregulation, respectively, of miRNA in the non-tumor tissues. Combinations 7, 9, 11 and 13 are explained in Materials and methods.

Figure 3.

Representative miRNAs detected in comparisons of the normal liver samples with tumor tissues. The upward and downward arrows indicate up- and downregulation, respectively, of miRNA in the tumor tissues. Combinations 6, 8, 10 and 12 are explained in Materials and methods.