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Hann et al. Hepatoma Res 2017;3:105-11 Hepatoma Research
DOI: 10.20517/2394-5079.2017.15
www.hrjournal.net
Original Article Open Access

Detection of urine DNA markers for monitoring

recurrent hepatocellular carcinoma

Hie-Won Hann , Surbhi Jain , Grace Park , Jamin D. Steffen , Wei Song , Ying-Hsiu Su 3
2
2
1
2
1
1 Liver Disease Prevention Center, Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
2 JBS Science, Inc., Doylestown, PA 18902, USA.
3 The Baruch S. Blumberg Institute, Doylestown, PA 18902, USA.
Correspondence to: Prof. Ying-Hsiu Su, The Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
E-mail: Ying-hsiu.su@bblumberg.org
How to cite this article: Hann HW, Jain S, Park G, Steffen JD, Song W, Su YH. Detection of urine DNA markers for monitoring recurrent hepatocellular
carcinoma. Hepatoma Res 2017;3:105-11.
ABSTRACT
Article history: Aim: This study aimed to explore the potential of detecting hepatocellular carcinoma (HCC)-
Received: 20-04-2017 associated DNA markers, TP53 249T mutations and aberrant methylation of RASSF1A
Accepted: 16-05-2017 and GSTP1 genes, for monitoring HCC recurrence. HCC remains a leading cause of death
Published: 06-06-2017 worldwide, with one of the fastest growing incidence rates in the US. While treatment options
are available and new ones emerging, there remains a poor prognosis of this disease mostly
Key words: due to its late diagnosis and high recurrence rate. Although there are no specific guidelines
Hepatocellular carcinoma, addressing how HCC recurrence should be monitored, recurrence is usually monitored by
recurrence, serum-alpha fetal protein and imaging methods such as magnetic resonance imaging (MRI).
circulating-tumor DNA, However, early detection of recurrent HCC remains limited, particularly at the site of treated
liver cancer, lesion. Methods: Here, the authors followed 10 patients that were treated for a primary HCC,
biomarker, and monitored for months or years later. At these follow-up visits, urine was collected and
urine tumor marker, tested retrospectively for 3 DNA biomarkers that associate with HCC development. Results:
hepatitis B virus This 10-patient study compared detection of urine DNA markers with MRI for monitoring
HCC recurrence. Five patients were confirmed by MRI for recurrence, and all 5 had detectable
DNA biomarkers up to 9 months before recurrence confirmation by MRI. Conclusion:
Overall, this suggests that detection of HCC-associated DNA markers in urine could provide
a promising tool to complement detection of recurrent HCC by imaging.

INTRODUCTION within 5 years) is mainly due to late detection and a
high recurrence rate. [1-5] Rates of recurrence range
Liver cancer is the sixth most common malignant from 15% for liver transplantation to nearly 100% for
neoplasm in the world and the second leading cause surgery or ablation. [6-10] Recurrence is most common
of cancer death worldwide, with an estimated 782,000 within 2 years. [11]
new liver cancer cases and 746,000 deaths during
2012. Hepatocellular carcinoma (HCC) constitutes Recently, a reduced recurrence rate has been
[1]
70-85% of all types of liver cancer. The high reported for hepatitis B virus (HBV)-associated HCC
[2]
mortality rate of HCC (where 85% of patients die with concomitant antiviral therapy following initial
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