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

Hepatoma Research ›› 2017, Vol. 3 : 105 -11.

PDF
Hepatoma Research ›› 2017, Vol. 3:105 -11. DOI: 10.20517/2394-5079.2017.15
Original Article
Original Article

Detection of urine DNA markers for monitoring recurrent hepatocellular carcinoma

Author information +
History +
PDF

Abstract

Aim: This study aimed to explore the potential of detecting hepatocellular carcinoma (HCC)-associated DNA markers, TP53 249T mutations and aberrant methylation of RASSF1A and GSTP1 genes, for monitoring HCC recurrence. HCC remains a leading cause of death 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 due to its late diagnosis and high recurrence rate. Although there are no specific guidelines addressing how HCC recurrence should be monitored, recurrence is usually monitored by serum-alpha fetal protein and imaging methods such as magnetic resonance imaging (MRI). However, early detection of recurrent HCC remains limited, particularly at the site of treated lesion.

Methods: Here, the authors followed 10 patients that were treated for a primary HCC, and monitored for months or years later. At these follow-up visits, urine was collected and tested retrospectively for 3 DNA biomarkers that associate with HCC development.

Results: 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.

Keywords

Hepatocellular carcinoma / recurrence / circulating-tumor DNA / liver cancer / biomarker / urine tumor marker / hepatitis B virus

Cite this article

Download citation ▾
Hie-Won Hann, Surbhi Jain, Grace Park, Jamin D. Steffen, Wei Song, Ying-Hsiu Su. Detection of urine DNA markers for monitoring recurrent hepatocellular carcinoma. Hepatoma Research, 2017, 3: 105-11 DOI:10.20517/2394-5079.2017.15

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Hung IF,Poon RT,Chui AH,Fung JY,Yuen JC,Choi O,Yuen MF.Risk factors and post-resection independent predictive score for the recurrence of hepatitis B-related hepatocellular carcinoma..PLoS One2016;11:e0148493

[2]

Chong CC,Ip PC,Cheung SY,Ho SC.Pre-operative predictors of post-hepatectomy recurrence of hepatocellular carcinoma: can we predict earlier?.Surgeon2012;10:260-6

[3]

Marrero JA.Hepatocellular carcinoma..Clin Liver Dis2006;10:339-51

[4]

Sherman M.Recurrence of hepatocellular carcinoma..N Engl J Med2008;359:2045-7

[5]

Lok A.Chronic hepatitis B..Hepatology2001;34:1225-41

[6]

Portolani N,Ghidoni S,Benetti A,Giulini SM.Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications..Ann Surg2006;243:229-35 PMCID:PMC1448919

[7]

Kamiyama T,Yokoo H,Tahara M,Shimamura T,Matsushita M.Recurrence patterns after hepatectomy of hepatocellular carcinoma: implication of Milan criteria utilization..Ann Surg Oncol2009;16:1560-71

[8]

Minami Y,Kudo M.Therapeutic response assessment of RFA for HCC: contrast-enhanced US, CT and MRI..World J Gastroenterol2014;20:4160-6 PMCID:PMC3989952

[9]

Minami Y.Imaging Modalities for assessment of treatment response to nonsurgical hepatocellular carcinoma therapy: contrast-enhanced US, CT, and MRI..Liver Cancer2015;4:106-14 PMCID:PMC4682875

[10]

Piao CY,Iwasaki Y,Kaneyoshi T,Hashimoto K,Terada R,Kobashi H,Shiratori Y.Lamivudine treatment in patients with HBV-related hepatocellular carcinoma -- using an untreated, matched control cohort..Acta Med Okayama2005;59:217-24

[11]

Poon RT,Ng IO,Liu CL.Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma..Cancer2000;89:500-7

[12]

Hann HW,Brown D,Rosato E,Hann RS,Dunn S.A long-term study of the effects of antiviral therapy on survival of patients with HBV-associated hepatocellular carcinoma (HCC) following local tumor ablation..Cancer Med2014;3:390-6 PMCID:PMC3987088

[13]

Kim BK,Kim DY,Kim KS,Moon BS,Chon CY,Ahn SH.Persistent hepatitis B viral replication affects recurrence of hepatocellular carcinoma after curative resection..Liver Int2008;28:393-401

[14]

Hann HW,Coben R.Prevention of new hepatocellular carcinoma with concomitant antiviral therapy in chronic hepatitis B patients whose initial tumor was successfully ablated..Int J Cancer2011;128:739-42

[15]

Chan AC,Yuen WK,Poon RT,Fan ST.Impact of antiviral therapy on the survival of patients after major hepatectomy for hepatitis B virus-related hepatocellular carcinoma..Arch Surg2011;146:675-81

[16]

Wu CY,Ho HJ,Kuo KN,Lin JT.Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection..JAMA2012;308:1906-14

[17]

Kuzuya T,Kumada T,Nakano I,Itoh A,Hayashi K,Goto H.Efficacy of antiviral therapy with lamivudine after initial treatment for hepatitis B virus-related hepatocellular carcinoma..J Gastroenterol Hepatol2007;22:1929-35

[18]

Hann HW,Yamada H,Coben R.Usefulness of highly sensitive AFP-L3 and DCP in surveillance for hepatocellular carcinoma in patients with a normal Alpha-Fetoprotein..J Med Microbiol Diagn2014;3:1-6

[19]

Carr BI,Wise M.Clinical evaluation of lens culinaris agglutinin-reactive α-fetoprotein and Des-γ-Carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States..Dig Dis Sci2007;52:776-82

[20]

Willatt JM,Adusumilli S.MR Imaging of hepatocellular carcinoma in the cirrhotic liver: challenges and controversies..Radiology2008;247:311-30

[21]

Yu JS.Hepatocellular carcinoma after transcatheter arterial chemoembolization: difficulties on imaging follow-up..Korean J Radiol2005;6:134-5 PMCID:PMC2685035

[22]

Zhao YJ,Li GC.Tumor markers for hepatocellular carcinoma..Mol Clin Oncol2013;1:593-8 PMCID:PMC3915636

[23]

Yin CQ,Qu Z,Chen H.Liquid biopsy of hepatocellular carcinoma: circulating tumor-derived biomarkers..Dis Markers2016;2016:1427849 PMCID:PMC4925990

[24]

Wan JC,Garcia-Corbacho J,Brenton JD,Pacey S,Rosenfeld N.Liquid biopsies come of age: towards implementation of circulating tumour DNA..Nat Rev Cancer2017;17:223-38

[25]

Su YH,Aiamkitsumrit B,Block TM.Detection of K-ras mutation in urine of patients with colorectal cancer..Cancer Biomarker2005;1:177-82

[26]

Su YH,Norton PA,Block TM.Detection of mutated K-ras DNA in urine, plasma and serum from patients with colorectal carcinoma or adenomatous polyps..Ann N Y Acad Sci2008;1137:197-201 PMCID:PMC2587049

[27]

Song BP,Lin SY,Block TM,Brenner DE.Detection of hypermethylated vimentin in urine of patients with colorectal cancer..J Mol Diagn2012;14:112-9 PMCID:PMC3349838

[28]

Su YH,Block TM,Botezatu I,Lichtenstein A,Tomei D.Transrenal DNA as a diagnostic tool: important technical notes..Ann N Y Acad Sci2004;1022:81-9

[29]

Lin SY,Jain S,Hu CT,Chen SH,Block TM.A locked nucleic acid clamp-mediated PCR assay for detection of a p53 codon 249 hotspot mutation in urine..J Mol Diagn2011;13:474-84 PMCID:PMC3157622

[30]

Jain S,Boldbaatar B,Hamilton JP,Chen SH,Block TM,Su YH.Differential methylation of the promoter and first exon of the RASSF1A gene in hepatocarcinogenesis..Hepatol Res2015;45:1110-23 PMCID:PMC4426255

[31]

Lin SY,Song W,Su YH.Strategic assay developments for detection of HBV 1762T/1764A double mutation in urine of patients with HBV-associated hepatocellular carcinomas. In: Hepatocellular Carcinoma - Clinical Research2012;139-54

[32]

Jain S,Chang KC,Hu CT,Hamilton JP,Chang TT,Song W,Block TM.Impact of the location of CpG methylation within the GSTP1 gene on its specificity as a DNA marker for hepatocellular carcinoma..PLoS One2012;7:e35789

[33]

Su YH,Song W.DNA markers in molecular diagnostics for hepatocellular carcinoma..Expert Rev Mol Diagn2014;14:803-17 PMCID:PMC4480673

[34]

Su YH,Brenner DE,Melkonyan H,Syngal S.Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer..J Mol Diagn2004;6:101-7

[35]

Su YH,Wang Z,Wang M,Block TM.Removal of high molecular weight DNA by carboxylated magnetic beads enhances the detection of mutated K-ras DNA in urine..Ann N Y Acad Sci2008;1137:82-91 PMCID:PMC2572261

[36]

Bruix J.Management of hepatocellular carcinoma..Hepatology2005;42:1208-36

PDF

51

Accesses

0

Citation

Detail

Sections
Recommended

/