Digestive Diseases and Sciences

, Volume 58, Issue 4, pp 1010–1015 | Cite as

Detection of TFPI2 Methylation in the Serum of Hepatocellular Carcinoma Patients

  • Feng-Kai Sun
  • Yu-Chen Fan
  • Jing Zhao
  • Feng Zhang
  • Shuai Gao
  • Ze-Hua Zhao
  • Qi Sun
  • Kai Wang
Original Article



DNA methylation plays a key role in hepatocellular carcinogenesis and progression. Analysis of aberrant methylation in serum DNA might provide a strategy for noninvasive detection of hepatocellular carcinoma (HCC).


To explore the feasibility of this approach, we compared TFPI2 methylation status in serum samples of HCC, chronic hepatitis B (CHB) patients and normal control groups using methylation-specific polymerase chain reaction.


Our results showed that the percentage of serum TFPI2 promoter methylation was significantly higher in the HCC group (46.5 %, 20/43) compared with the CHB group (16.7 %, 4/24; p = 0.015) and the normal control group (19.2 %, 5/26; p = 0.022), respectively, indicating that TFPI2 methylation frequently existed in the serum of HCC patients. In our study, the detection rate of HCC using serum TFPI2 methylation was 46.5 % (20/43), which was quite close to the reported detection rate of α-fetoprotein (54 %). In cases where we combined both markers, the detection rate was 61.0 %, suggesting that serum TFPI2 methylation could be used as a potential marker for noninvasive detection of HCC. Then, we evaluated the correlation between the serum TFPI2 methylation status of HCC patients and their clinicopathological parameters. Patients with advanced TNM stage (III–IV) showed a significantly elevated serum methylation percentage of TFPI2 in comparison with those with early TNM stage (I–II) (p = 0.025). Moreover, TFPI2 methylation was observed more frequently according to the progression of TNM stage.


Our present study suggested that TFPI2 methylation in serum tended to be detected more easily in patients with advanced HCC and might be used as a predictor of HCC progression.


TFPI2 Methylation Serum Hepatocellular carcinoma 



American Association for the Study of Liver Diseases




Circulating cell-free DNA


Chronic hepatitis B


Extracellular matrix


Hepatitis B virus


Hepatocellular carcinoma


Matrix metalloproteinases


Methylation-specific polymerase chain reaction


Tissue factor pathway inhibitor-2





This work was supported by grants from the National Key Technology R&D Program (2011BAZ03191), Key Project of Chinese Ministry of Science and Technology (2012ZX10002007), National Natural Science Foundation of China (81171579,81201287), Natural Science Foundation of Shandong Province (ZR2010HM070, ZR2010HQ040), Independent Innovation Foundation of Shandong University (IIFSDU, 2010TS013), and Science and Technology Development Plan Project of Shandong Province (2012GGE27053).

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Feng-Kai Sun
    • 1
  • Yu-Chen Fan
    • 1
    • 2
  • Jing Zhao
    • 1
  • Feng Zhang
    • 1
  • Shuai Gao
    • 1
  • Ze-Hua Zhao
    • 1
  • Qi Sun
    • 3
  • Kai Wang
    • 1
    • 2
  1. 1.Department of HepatologyQilu Hospital of Shandong UniversityJinanChina
  2. 2.Institute of HepatologyShandong UniversityJinanChina
  3. 3.Department of Hepatobiliary SurgeryQilu Hospital of Shandong UniversityJinanChina

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