J Korean Med Sci.  2017 Feb;32(2):212-220. 10.3346/jkms.2017.32.2.212.

An Explorative Analysis for the Role of Serum miR-10b-3p Levels in Predicting Response to Sorafenib in Patients with Advanced Hepatocellular Carcinoma

• Yoon EL
• Yeon JE
• Ko E
• Lee HJ
• Je JH
• Yoo YJ
• Kang SH
• Suh SJ
• Kim JH
• Seo YS
• Yim HJ
• Byun KS

• KMID: 2364164
• DOI: http://doi.org/10.3346/jkms.2017.32.2.212

Abstract

The prognostic role of aberrant serum miRNA expression for predicting response to sorafenib treatment in advanced hepatocellular carcinoma (HCC) patients has not been well characterized. We aimed to identify specific serum miRNAs that are associated with positive radiologic responses or improved survival in sorafenib-treated HCC patients. miR-18a, miR-21, miR-139-5p, miR-221, miR-224, and miR-10b-3p, were selected for analysis. Serum samples from 24 patients with advanced stage HCC and 25 patients with liver cirrhosis (LC) were analyzed. All of the miRNAs except miR-21 were found to be upregulated in serum samples from HCC patients. None of the miRNAs assayed differed significantly in terms of expression between the responder and non-responder groups among HCC patients. However, miR-10b-3p levels were significantly higher in the subgroup of HCC patients with worse overall survival (fold change = 5.8, P = 0.008). Serum miRNA-10b-3p was upregulated in the presence of macrovascular invasion (MVI), and those with higher serum miRNA-10b-3p had significantly shorter survival during treatment (P = 0.042). Although no single serum miRNA was predictive of response to sorafenib treatment, analysis of serum miR-10b-3p levels may be valuable for diagnosis of HCC and prediction of survival of sorafenib-treated patients.

Keyword

Serum MicroRNA; Hepatocellular Carcinoma; Sorafenib; Survival; Macrovascular Invasion

MeSH Terms

Carcinoma, Hepatocellular*
Diagnosis
Humans
Liver Cirrhosis
MicroRNAs
MicroRNAs

Figure

• 

  Fig. 1 Expression of serum miRNAs in LC and HCC patients. We selected 6 candidate miRNAs reported to be aberrantly expressed in HCC tissue specimens compared with non-cancerous liver tissues. With the exception of miR-21, all of the chosen miRNAs are significantly overexpressed in serum samples from HCC patients compared with those from LC patients. The numbers shown above each box represent the median fold changes compared to the median value of the samples obtained from LC patients. The box plots show the median (horizontal bar) and the interquartile ranges, and the bars show the minimum and maximum values. LC (n = 25); HCC (n = 24). LC = liver cirrhosis, HCC = hepatocellular carcinoma.

• 

  Fig. 2 Expression of serum miRNAs and overall survival. The expression of 6 candidate miRNAs was compared between the better and the worse survival groups of HCC patients. miR-139-5p is significantly downregulated in serum samples from the worse survival group (P = 0.005), while miR-10b-3p was significantly upregulated in samples from the worse survival group (P = 0.008). The numbers shown above each box represent median fold changes compared to the median value of samples for the better survival group. Better survival (n = 14); worse survival (n = 10). HCC = hepatocellular carcinoma.

• 

  Fig. 3 Expression of miR-10b-3p and miR-139-5p and the invasiveness of HCC. Levels of serum miR-10b-3p were significantly higher in patients with MVI (P = 0.001). Expression of miR-139-5p in serum samples did not differ significantly between patients with and without MVI. The numbers shown above each box represent the median fold changes compared to the median value of samples obtained from HCC patients without MVI. MVI (−), without MVI (n = 12); MVI (+), with MVI (n = 12). HCC = hepatocellular carcinoma, MVI = macrovascular invasion.

• 

  Fig. 4 Comparison of median overall survival between the low and high serum miR-10b-3p groups. The median survival of the low serum miR-10b-3p group was significantly longer than that of the high serum miR-10b-3p group (HR, 4.99; 95% CI, 4.60–5.57; P = 0.042). The numbers shown below the graph represent patients who survived until the time on the x-axis after the initiation of sorafenib treatment. HR = hazard ratio, CI = confidence interval.

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