Hepatology International

, Volume 7, Issue 1, pp 199–207 | Cite as

Serum miR-483-5p as a potential biomarker to detect hepatocellular carcinoma

  • Zhoujing Zhang
  • Shengxiang Ge
  • Xiaomin Wang
  • Quan Yuan
  • Qiang Yan
  • Huiming Ye
  • Yaojian Che
  • Yanyan Lin
  • Jun Zhang
  • Pingguo LiuEmail author
Original Article


Background and goals

There are no highly sensitive and specific minimally invasive biomarkers for hepatocellular carcinoma (HCC) to date. The objective of this study was to identify serum microRNAs (miRNAs) as potential HCC biomarkers.


Using miRCURY LNA™ microRNA arrays, the levels of circulating miRNAs in the serum of patients with HCC were compared and controls were matched. Then 253 subjects (112 HCC, 85 chronic hepatitis B [CHB], and 56 healthy controls) were recruited and 12 serum miRNAs were compared by quantitative real-time polymerase chain reaction (qRT-PCR). It was followed by the comparison of serum miRNA concentrations before and after the surgical resection in HCC group.


Median levels of miR-483-5p and miR-500a were higher in HCC patients than in patients with CHB and in healthy controls (p < 0.0001), but there were no differences between CHB patients and healthy controls (p > 0.05) and miR-483-5p levels were significantly reduced in serum samples obtained 30 days after surgical resection (p < 0.0001). The area under receiver operating characteristic curves of miR-483-5p and miR-500a was 74% (cutoff [Ct] value = 2.824, sensitivity = 74%, and specificity = 66%) and 66% (Ct value = 1.830, sensitivity = 74%, and specificity = 51%) for the prediction of HCC, respectively. In detecting HCC, combining α-fetoprotein (AFP) and serum miR-483-5p (sensitivity = 81% and specificity = 83%) was better than AFP alone (sensitivity = 78%, specificity = 70%).


Our observations suggest that serum miR-483-5p and miR-500a might serve as novel, noninvasive biomarkers for HCC. Serum miR-483-5p might complement AFP in detecting HCC.


Biomarker Hepatocellular carcinoma Microrna miR-483-5p Serum 



This study was supported by grants from the Medical Innovation Project of Fujian Province, China (2009-CXB-55) and the Science and Technology Project of Xiamen, China (3502Z20100002).

Conflicts of interest

The authors confirm that there are no conflicts of interest.

Supplementary material

12072_2012_9341_MOESM1_ESM.tif (1.8 mb)
Fig. S1. Scatter plot analysis of the miRNA Array (A–F). a HCC-1 versus Control-1; b HCC-1 versus Control-2; c HCC-2 versus Control-1; d HCC-2 versus Control-2; e HCC-1 versus HCC-2; and f Control-1 versus Control-2. (TIFF 1888 kb)
12072_2012_9341_MOESM2_ESM.tif (123 kb)
Fig. S2. The miR-483-5p IGF-2 relative expression level in liver tissue. The miR-483-5p relative expression level (according to U6, [a]), IGF-2 expression level (according to GAPDH, [b]), and IGF-2 protein expression level (c) in 10 HCC tissue control to paired normal liver tissue. Primer and probe sequences for real-time PCR: U6, forward: ctgcgcaaggatgaca, reverse: tatggaacgcttcacg. IGF-2, forward: actgcttccaggtgtcatatt, reverse: cctggagacgtactgtgcta. probe: FAM–cggacaacttccccagataccccg-BHQ-1. GAPDH, forward: ggcgatgctggcgctgagtac, reverse: tggtccacacccatgacga. probe: ROX-ttcaccaccatggagaaggctggg-BHQ-2. Antibody used for IGF-2 western blot were purchased from abcam, NO. Anti-IGF2 antibody (ab9574). (TIFF 123 kb)
12072_2012_9341_MOESM3_ESM.tif (1.9 mb)
Fig. S3. The qRT-PCR amplification curve of miR-483-5p, miR-500a, and Ath-miR-156a (A–C). The qRT-PCR amplification curve of miR-483-5p, miR-500a, and Ath-miR-156a, using miRNAs standard preparation and analysis were performed on CFX Manager (Bio-Rad). Tenfold serial dilution of miRNA was used to generate the standard curves. (TIFF 1958 kb)
12072_2012_9341_MOESM4_ESM.tif (3.1 mb)
Fig. S4. Initial cluster result of Fig. 1 and Table S3. (TIFF 3151 kb)
12072_2012_9341_MOESM5_ESM.doc (2.9 mb)
Supplementary material 5 (DOC 2944 kb)


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Copyright information

© Asian Pacific Association for the Study of the Liver 2012

Authors and Affiliations

  • Zhoujing Zhang
    • 1
  • Shengxiang Ge
    • 2
  • Xiaomin Wang
    • 1
  • Quan Yuan
    • 2
  • Qiang Yan
    • 2
  • Huiming Ye
    • 1
  • Yaojian Che
    • 2
  • Yanyan Lin
    • 1
  • Jun Zhang
    • 2
  • Pingguo Liu
    • 1
    Email author
  1. 1.Clinical Laboratory CenterZhongshan Hospital of Xiamen UniversityXiamenChina
  2. 2.National Institute of Diagnostic and Vaccine Development in Infectious DiseaseXiamen UniversityXiamenChina

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