Expression profiling of serum microRNA-101 in HBV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma - PubMed (original) (raw)
. 2014 Sep;15(9):1248-55.
doi: 10.4161/cbt.29688. Epub 2014 Jun 27.
Affiliations
- PMID: 24971953
- PMCID: PMC4128867
- DOI: 10.4161/cbt.29688
Expression profiling of serum microRNA-101 in HBV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma
Yun Xie et al. Cancer Biol Ther. 2014 Sep.
Abstract
MicroRNAs (miRNAs) represent a class of evolutionarily conserved, non-coding small RNAs (18-25 nt) that have emerged as master regulators of several biological processes. Recently, circulating miRNAs have also been reported to be promising biomarkers for various pathological conditions. In the present study, we report the comparative expression profiling of microRNA-101 (miR-101) in serum and tissue samples from chronic hepatitis B (CHB), HBV-associated liver cirrhosis (HBV-LC), and HBV-associated hepatocellular carcinoma (HBV-HCC) patients and healthy controls. The serum miR-101 levels were found to be significantly downregulated in the HBV-HCC patients compared with the HBV-LC patients (P<0.001), CHB patients (P<0.001) and healthy controls but were upregulated in the HBV-LC patients compared with the CHB patients (P<0.001) and healthy controls (P<0.001). Consistent with the serum data, the expression of miR-101 was also upregulated and downregulated in the HBV-LC and HBV-HCC tissue samples, respectively. A receiver operating characteristic (ROC) analysis of serum miR-101 yielded an area under the ROC curve (AUC) of 0.976 with 95.5% sensitivity and 90.2% specificity when differentiating between HBV-HCC and HBV-LC. Our results suggest that the serum miR-101 level can serve as a potential non-invasive biomarker to differentiate HBV-HCC from HBV-LC.
Keywords: circulating microRNA; expression profiling; hepatitis B; hepatocellular carcinoma; microRNA-101.
Figures
Figure 1. The expression levels of miR-101 in liver tissues. In situ hybridization was performed using locked nucleic acid (LNA)-modified probes for miR-101. Brown yellow staining in the cytoplasm represents positive staining for miR-101. (A) Normal liver tissues were graded positive for miR-101. (B) CHB liver tissues were graded positive for miR-101. (C) HBV-LC tissues were graded strong positive for miR-101. (D) HBV-HCC tissues were graded negative for miR-101. (E) The level of miR-101 expression in HBV-LC patients is higher than in healthy subjects and CHB patients, while it is lower in HBV-HCC patients. (* represents P < 0.05.)
Figure 2. Serum miR-101 levels in healthy subjects, patients with CHB, patients with HBV-LC and patients with HBV-HCC. The median level of serum miR-101 was significantly higher in patients with HBV-LC than in patients with CHB or healthy subjects (P < 0.001), whereas the median level was significantly lower in patients with HBV-HCC than in healthy subjects (P = 0.012) or patients with HBV-LC (P < 0.001). The lines represent the range, median and quartiles of relative miRNA expression (ΔCt values) measured by qRT-PCR.
Figure 3. ROC curve analysis of serum miR-101 for discriminating; (A) HBV-LC patients and healthy subjects, (B) HBV-HCC patients and healthy subjects.
Figure 4. ROC curve analysis of serum miR-101 for discriminating; (A) CHB patients from HBV-LC patients, (B) CHB patients from HBV-HCC patients, (C) HBV-LC patients from HBV-HCC patients, (D) AFP alone for discriminating HBV-LC from HBV-HCC patients. (E) AFP in combination with miR-101 for discriminating HBV-HCC from HBV-LC patients.
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