| Hepatocellular carcinoma(HCC), the major form of primary liver cancer, has exhibited an increase in morbidity and mortality. Thus far, no perfect markers for the early detection of HCC have been identified. The majority of patients with HCC are usually diagnosed at advanced stages, which are associated with a poor prognosis and low survival rates owing to a lack of effective treatment. Accordingly, searching for a sensitive and specific biomarker to screen for early-stage HCC remains essential. In fact, several HCC-related mi RNAs have been found to be deregulated in the serum or plasma of patients with HCC. Some aberrant circulating mi RNAs may even have diagnostic value for HCC. In addition, whether HCC-specific circulating mi RNAs are expressed differently in the HBV-related small HCC compared to other HBV-related benign liver diseases has not been reported. The identification of aberrant circulating mi RNAs in HBV-related small HCC may contribute to the early diagnosis of HBV-positive HCC.OBJECTIVE: We sought to determine the differentially expressed circulating micro RNAs in patients with hepatitis B virus(HBV)-positive small hepatocellular carcinoma(HCC) compared to other HBV-positive benign liver diseases.METHODS: The mi Script mi RNA PCR Array was used to detect the levels of 84 mi RNAs in plasma or serum samples of patients with HBV-related small HCC(23 cases), liver cirrhosis(LC)(20 cases), chronic hepatitis B(CHB)(20 cases) and healthy controls(16 cases). Mi RNAs with fold-change values ≥2 or ≤0.5 compared to healthy controls were considered to be deregulated mi RNAs. Then, select serum samples of patients with HCC(30 cases), LC(30 cases), hepatitis(30 cases) and healthy controls(30 cases), and extract total RNA. The expression of mi R-222 in each group was detected using quantitative real-time reverse-transcription polymerase chain reaction(q RT-PCR) to validate the screening results.RESULTS: The results of duplicate plasma experiments were not reliable. Comprehensive analysis of the two serum experiments showed that the quality controls all met the requirements. We found 18 differentially expressed mi RNAs. Relative to healthy controls, nine(mi R-17, mi R-195, mi R-19 a, mi R-19 b, mi R-20 a,mi R-25, mi R-92 a, mi R-15 b, mi R-16), three(mi R-195, mi R-25, mi R-16), and 11(mi R-100, mi R-17, mi R-18 a, mi R-195, mi R-19 a, mi R-20 a, mi R-223, mi R-25, mi R-145, mi R-15 b, mi R-16) mi RNAs were up-regulated in the CHB group, LC group and small HCC group, respectively. In contrast, one(mi R-205), three(mi R-125b、mi R-205、mi R-26b), and three(mi R-200a、mi R-205、mi R-222) mi RNAs were down-regulated in the same patient groups, respectively. Interestingly, mi R-195, mi R-25 and mi R-16 were up-regulated, and mi R-205 was down-regulated, in all three experimental groups. Moreover, only in the HCC group, mi R-18 a, mi R-100, mi R-145 and mi R-223 were up-regulated 3.48-, 2.95-, 2.12- and 3.91-fold, respectively, and mi R-200 a and mi R-222 were down-regulated 2.56- and 2.00- fold, respectively. The screening results were verified further by the expression of mi R-222. The relative expression of mi R-222 was 1.799±1.898 in the control group, 2.210±2.340 in the hepatitis group, 2.167±2.173 in the LC group, and 1.056±1.024 in the small HCC group(P>0.05). Although there was no statistically significant difference, the relative expression of mi R-222 was declined relatively in HCC group than in the control group.CONCLUSIONS: Our study demonstrated the presence of six differentially expressed serum micro RNAs in HBV-positive small HCC compared to other benign liver diseases associated with HBV. The expression of mi R-222 was declined in HCC group than in the control group, suggesting that mi R-222 may be related to the development of HCC. |
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