FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3161243576> ?p ?o ?g. }

• W3161243576 endingPage "100304" @default.
• W3161243576 startingPage "100304" @default.
• W3161243576 abstract "Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Its incidence is rising faster than any other cancer in the United States and it remains one of the leading causes of cancer-related deaths worldwide. While advances in massive parallel sequencing and integration of ‘omics information have transformed the field of oncology, tissue access is often limited in HCC and a single biopsy is poorly representative of the known genetic heterogeneity of tumours. Liquid biopsy has emerged as a promising strategy for analysing circulating tumour components including circulating tumour DNA. Cell-free DNA and tumour DNA are derived from necrotic, apoptotic and living eukaryotic cells. The profiling of genetic and epigenetic alterations in circulating cell-free DNA has potential clinical applications including early disease detection, prediction of treatment response and prognostication in real time. Novel biomarker candidates for disease detection and monitoring are under study. Of these, methylation analyses of circulating tumour DNA have shown promising performance for early HCC detection in at-risk patients. Assessments of assay performance in longitudinal validation cohorts are ongoing. Implementation of liquid biopsy for HCC will likely improve upon the current surveillance strategy. This review summarises the most recent developments on the role and utility of circulating cell-free DNA in the detection and management of HCC. Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Its incidence is rising faster than any other cancer in the United States and it remains one of the leading causes of cancer-related deaths worldwide. While advances in massive parallel sequencing and integration of ‘omics information have transformed the field of oncology, tissue access is often limited in HCC and a single biopsy is poorly representative of the known genetic heterogeneity of tumours. Liquid biopsy has emerged as a promising strategy for analysing circulating tumour components including circulating tumour DNA. Cell-free DNA and tumour DNA are derived from necrotic, apoptotic and living eukaryotic cells. The profiling of genetic and epigenetic alterations in circulating cell-free DNA has potential clinical applications including early disease detection, prediction of treatment response and prognostication in real time. Novel biomarker candidates for disease detection and monitoring are under study. Of these, methylation analyses of circulating tumour DNA have shown promising performance for early HCC detection in at-risk patients. Assessments of assay performance in longitudinal validation cohorts are ongoing. Implementation of liquid biopsy for HCC will likely improve upon the current surveillance strategy. This review summarises the most recent developments on the role and utility of circulating cell-free DNA in the detection and management of HCC. Key points•Early detection○Early detection of hepatocellular carcinoma leads to early curative treatment and improves survival.○Several methylation panels assayed from plasma DNA have demonstrated high sensitivity and specificity in detecting early disease in at-risk individuals.•Potential clinical utility of cell-free DNA○Longitudinal prospective studies are ongoing.○Detect cancer in individuals at high risk.○Measure residual disease following surgery, ablation or transplant with risk stratification for adjuvant therapy.○Enable treatment selection.○Elucidate mechanisms of resistance and disease progression. •Early detection○Early detection of hepatocellular carcinoma leads to early curative treatment and improves survival.○Several methylation panels assayed from plasma DNA have demonstrated high sensitivity and specificity in detecting early disease in at-risk individuals.•Potential clinical utility of cell-free DNA○Longitudinal prospective studies are ongoing.○Detect cancer in individuals at high risk.○Measure residual disease following surgery, ablation or transplant with risk stratification for adjuvant therapy.○Enable treatment selection.○Elucidate mechanisms of resistance and disease progression. Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is one of the leading causes of cancer-related deaths worldwide.[1]Akinyemiju T. Abera S. Ahmed M. Alam N. Alemayohu M.A. Allen C. et al.The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level.JAMA Oncol. 2017; 98121: 1683-1691Google Scholar Each year, more than 800,000 individuals are diagnosed globally. The incidence of HCC is rising faster than that of any other cancer in the United States,[2]Henley S.J. Ward E.M. Scott S. Ma J. Anderson R.N. Firth A.U. et al.Annual report to the nation on the status of cancer, part I: national cancer statistics.Cancer. 2020; 126: 2225-2249Crossref PubMed Scopus (243) Google Scholar driven by HCV-associated cirrhosis and the rising prevalence of non-alcoholic fatty liver disease.[3]White D.L. Thrift A.P. Kanwal F. Davila J. El-Serag H.B. Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012.Gastroenterology. 2017; 152 (812-820.e5)Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar The annual risk of developing HCC in high risk groups, including chronic carriers of HBV and patients with cirrhosis (of infectious, metabolic or alcoholic aetiology) is 2–4% per year.[4]El-Serag H.B. Hepatocellular carcinoma.N Engl J Med. 2011; 365: 1118-1127Crossref PubMed Scopus (2983) Google Scholar Several studies have demonstrated that HCC surveillance is associated with early detection, receipt of curative treatment, and improved survival.[5]Singal A.G. Pillai A. Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis.Plos Med. 2014; 11e1001624Crossref PubMed Scopus (419) Google Scholar,[6]Zhang B.H. Yang B.H. Tang Z.Y. Randomized controlled trial of screening for hepatocellular carcinoma.J Canc Res Clin Oncol. 2004; 130: 417-422Crossref PubMed Scopus (1000) Google Scholar Consequently, for those patients at high risk, clinical practice guidelines recommend biannual HCC surveillance by ultrasound imaging with or without serum alpha-fetoprotein (AFP) testing.[7]EASL Clinical Practice GuidelinesManagement of hepatocellular carcinoma.J Hepatol. 2018; 69: 182-236Abstract Full Text Full Text PDF PubMed Scopus (2898) Google Scholar,[8]Marrero J.A. Kulik L.M. Sirlin C.B. Zhu A.X. Finn R.S. Abecassis M.M. et al.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases.Hepatology. 2018; 68: 723-750Crossref PubMed Scopus (1394) Google Scholar However, several limitations exist with this approach; the aggregate sensitivity is low at 63%, especially for those with early disease within and outside of Milan criteria for liver transplantation, and surveillance is underutilised.[9]Tzartzeva K. Obi J. Rich N.E. Parikh N.D. Marrero J.A. Yopp A. et al.Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis.Gastroenterology. 2018; 154: 1706-1718.e1Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar A recent meta-analysis involving more than 118,000 patients showed a pooled estimate for surveillance use of 24% (95% CI 18.4–30.1), with variable usage depending on the level of care (subspecialty care or primary care).[10]Wolf E. Rich N.E. Marrero J.A. Parikh N.D. Singal A.G. Use of hepatocellular carcinoma surveillance in patients with cirrhosis: a systematic review and meta-analysis.Hepatology. 2020; Google Scholar Furthermore, the diagnosis of HCC is made using radiological or histological criteria. Liver biopsy is invasive, poorly reflects the temporal and spatial heterogeneity within the tumour, and is often not available. This presents a large window of opportunity for the development of novel biomarkers that can detect HCC early and can accurately predict outcomes. Currently, liver resection and local ablation remain the mainstays of curative therapy, as liver transplant is limited by the size of the donor pool and stringent eligibility criteria.[11]Mazzaferro V. Regalia E. Doci R. Andreola S. Pulvirenti A. Bozzetti F. et al.Carcinomas in patients with cirrhosis.N Engl J Med. 1996; 334: 693-699Crossref PubMed Scopus (5399) Google Scholar,[12]Yao F.Y. Ferrell L. Bass N.M. Watson J.J. Bacchetti P. Venook A. et al.Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival.Hepatology. 2001; 33: 1394-1403Crossref PubMed Scopus (1673) Google Scholar After resection, recurrence within the residual cirrhotic liver is high, with more than 50% of patients developing HCC recurrence within 3 years and 70–80% recurring within 5 years; the 5-year survival rate for these patients is approximately 40–50%.13Chapman W.C. Klintmalm G. Hemming A. Vachharajani N. Majella Doyle M.B. Dematteo R. et al.Surgical treatment of hepatocellular carcinoma in North America: can hepatic resection still be justified?.J Am Coll Surgeons. 2015; 220: 628-637Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 14Li Y. Xia Y. Li J. Wu D. Wan X. Wang K. et al.Prognostic nomograms for pre- and postoperative predictions of long-term survival for patients who underwent liver resection for huge hepatocellular carcinoma.J Am Coll Surgeons. 2015; 221: 962-974.e4Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 15She W.H. Chok K.S.H. Ang S.F. Ng E.S.H. Li H. Ong Y.H. et al.The Singapore Liver Cancer Recurrence (SLICER) Score for relapse prediction in patients with surgically resected hepatocellular carcinoma.Ann Surg. 2015; 261 (962-974.e4)Google Scholar, 16Shim J.H. Jun M.J. Han S. Lee Y.J. Lee S.G. Kim K.M. et al.Prognostic nomograms for prediction of recurrence and survival after curative liver resection for hepatocellular carcinoma.Ann Surg. 2015; 261: 939-946Crossref PubMed Scopus (141) Google Scholar, 17Yang P. Qiu J. Li J. Wu D. Wan X. Lau W.Y. et al.Nomograms for pre-and postoperative prediction of long-term survival for patients who under went hepatectomy for multiple hepatocellular carcinomas.Ann Surg. 2016; 263: 778-786Crossref PubMed Scopus (44) Google Scholar Over the last few years, significant advances have been made in the management of patients with advanced HCC. Since 2007, sorafenib[18]Llovet J.M. Ricci S. Mazzaferro V. Hilgard P. Gane E. Blanc J.F. et al.Sorafenib in advanced hepatocellular carcinoma.N Engl J Med. 2008; 359: 378-390Crossref PubMed Scopus (8111) Google Scholar – an oral multikinase inhibitor – and subsequently lenvatinib,[19]Kudo M. Finn R.S. Qin S. Han K.H. Ikeda K. Piscaglia F. et al.Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial.The Lancet. 2018; 391: 1163-1173Abstract Full Text Full Text PDF PubMed Scopus (1727) Google Scholar have been the first-line systemic therapies for patients with advanced HCC. Recently, atezolizumab – an anti-PD-L1 antibody – in combination with bevacizumab – a monoclonal anti-VEGF antibody – showed superior outcomes (67.2% overall survival (OS) at 12 months vs. 54.6% with sorafenib),[20]Finn R.S. Qin S. Ikeda M. Galle P.R. Ducreux M. Kim T.Y. et al.Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma.N Engl J Med. 2020; 382: 1894-1905Crossref PubMed Scopus (1172) Google Scholar which led to FDA approval of this combination as first-line systemic treatment for advanced HCC. Second-line treatments include the multikinase inhibitors cabozantinib[21]Abou-Alfa G.K. Meyer T. Cheng A.L. El-Khoueiry A.B. Rimassa L. Ryoo B.Y. et al.Cabozantinib in patients with advanced and progressing hepatocellular carcinoma.N Engl J Med. 2018; 379: 54-63Crossref PubMed Scopus (867) Google Scholar and regorafenib,[22]Bruix J. Qin S. Merle P. Granito A. Huang Y.H. Bodoky G. et al.Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet. 2017; 389: 56-66Abstract Full Text Full Text PDF PubMed Scopus (1738) Google Scholar the anti-VEGF antibody ramucirumab,[23]Zhu A.X. Kang Y.K. Yen C.J. Finn R.S. Galle P.R. Llovet J.M. et al.Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Oncol. 2019; 20: 282-296Abstract Full Text Full Text PDF PubMed Scopus (593) Google Scholar the anti-PD1 antibodies nivolumab,[24]El-Khoueiry A.B. Sangro B. Yau T. Crocenzi T.S. Kudo M. Hsu C. et al.Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.Lancet. 2017; 389: 2492-2502Abstract Full Text Full Text PDF PubMed Scopus (1936) Google Scholar pembrolizumab[25]Zhu A.X. Finn R.S. Edeline J. Cattan S. Ogasawara S. Palmer D. et al.Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial.Lancet Oncol. 2018; 19: 940-952Abstract Full Text Full Text PDF PubMed Scopus (972) Google Scholar and the combination of nivolumab with the CTLA-4 inhibitor, ipilimumab.[26]Yau T. Kang Y.-K. Kim T.-Y. El-Khoueiry A.B. Santoro A. Sangro B. et al.Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial.JAMA Oncol. 2020; 6 (e204564-e204564)Crossref Scopus (194) Google Scholar With the exception of ramucirumab, for which AFP >400 ng/dl is associated with response, there are no biomarkers to stratify patients with HCC. Thus, emerging novel biomarkers such as circulating tumour DNA (ctDNA) – the tumour-specific component of circulating cell-free DNA (cfDNA) – have garnered substantial attention in the last few years, owing to their potential to address 3 key clinical problems. First, can they be used to detect early HCC at a stage when current surveillance modalities are insensitive and difficult to access? Second, will cfDNA levels obtained before or after surgery be prognostic of long-term outcomes? Lastly, can cfDNA associated with HCC predict response to treatment? In this review, we discuss the most recent developments on the role and utility of circulating cfDNA in the detection and prognostication of HCC. Liquid biopsy, the minimally invasive assay of circulating cancer-associated biomarkers such as circulating nucleic acids, circulating tumour cells, miRNAs and exosomes, has several potential clinical applications.[27]Felden J.V. Craig A.J. Villanueva A. Role of circulating tumor DNA to help decision-making in hepatocellular carcinoma.Oncoscience. 2018; 5 (1-1)Crossref Google Scholar,[28]Li J. Han X. Yu X. Xu Z. Yang G. Liu B. et al.Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA.J Exp Clin Canc Res. 2018; 37: 1-13Crossref PubMed Scopus (48) Google Scholar Of these, the analysis of cfDNA is currently the most promising in HCC. Circulating cfDNA refers to fragments of DNA detected in both healthy individuals and patients with cancer.[29]Mandel P. Metais P. Nuclear acids in human blood plasma.C R Seances Soc Biol Fil. 1948; 142: 241-243PubMed Google Scholar,[30]Sorenson G.D. Pribish D.M. Valone F.H. Memoli V.A. Bzik D.J. Yao S.L. Soluble normal and mutated DNA sequences from single-copy genes in human blood.Canc Epidemiol Biomark Prev. 1994; 3: 67-71PubMed Google Scholar cfDNA mostly comprises DNA shed from the normal turnover of lymphoid and myeloid cells,[31]Snyder M.W. Kircher M. Hill A.J. Daza R.M. Shendure J. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin.Cell. 2016; 164: 57-68Abstract Full Text Full Text PDF PubMed Scopus (557) Google Scholar with ctDNA making up less than 1% of total cfDNA in patients with cancer (Fig. 1).[32]Newman A.M. Bratman S.V. To J. Wynne J.F. Eclov N.C. Modlin L.A. et al.An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage.Nat Med. 2014; 20: 548-554Crossref PubMed Scopus (1231) Google Scholar Most circulating cfDNA fragments are double-stranded, exist in plasma or serum, and are longer than 167 base pairs.33Jiang P. Chan C.W. Chan K.C. Cheng S.H. Wong J. Wong V.W. et al.Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients.Proc Natl Acad Sci U S A. 2015; 112: E1317-E1325Crossref PubMed Scopus (353) Google Scholar, 34Mouliere F. Chandrananda D. Piskorz A.M. Moore E.K. Morris J. Ahlborn L.B. et al.Enhanced detection of circulating tumor DNA by fragment size analysis.Sci Transl Med. 2018; 10Crossref PubMed Scopus (292) Google Scholar, 35Underhill H.R. Kitzman J.O. Hellwig S. Welker N.C. Daza R. Baker D.N. et al.Fragment length of circulating tumor DNA.Plos Genet. 2016; 12e1006162Crossref PubMed Scopus (311) Google Scholar This size approximates the length of DNA wrapped around a single nucleosome, which may protect DNA from degradation by blood nucleases. In contrast, ctDNA fragments, which are released by necrotic or apoptotic tumour cells, are typically shorter than 150 base pairs; these size differences, as well as sequence variation or epigenetic modifications, may be exploited to identify tumour-specific sequences.[34]Mouliere F. Chandrananda D. Piskorz A.M. Moore E.K. Morris J. Ahlborn L.B. et al.Enhanced detection of circulating tumor DNA by fragment size analysis.Sci Transl Med. 2018; 10Crossref PubMed Scopus (292) Google Scholar Indeed, cancer-specific alterations in ctDNA are measurable by next-generation sequencing (NGS) and targeted PCR-based technologies.[36]Diaz Jr., L.A. Bardelli A. Liquid biopsies: genotyping circulating tumor DNA.J Clin Oncol. 2014; 32: 579-586Crossref PubMed Scopus (1364) Google Scholar Early studies demonstrated that ctDNA harbour molecular characteristics known to be present in the genomic DNA of cancers, such as methylation changes37Balgkouranidou I. Chimonidou M. Milaki G. Tsarouxa E.G. Kakolyris S. Welch D.R. et al.Breast cancer metastasis suppressor-1 promoter methylation in cell-free DNA provides prognostic information in non-small cell lung cancer.Br J Canc. 2014; 110: 2054-2062Crossref PubMed Scopus (51) Google Scholar, 38Chan K.C. Jiang P. Chan C.W. Sun K. Wong J. Hui E.P. et al.Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing.Proc Natl Acad Sci U S A. 2013; 110: 18761-18768Crossref PubMed Scopus (248) Google Scholar, 39Chan K.C. Lai P.B. Mok T.S. Chan H.L. Ding C. Yeung S.W. et al.Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma.Clin Chem. 2008; 54: 1528-1536Crossref PubMed Scopus (124) Google Scholar, 40Wong I.H. Lo Y.M. Zhang J. Liew C.T. Ng M.H. Wong N. et al.Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients.Canc Res. 1999; 59: 71-73PubMed Google Scholar and point mutations,41Huang A. Zhang X. Zhou S.L. Cao Y. Huang X.W. Fan J. et al.Detecting circulating tumor DNA in hepatocellular carcinoma patients using droplet digital PCR is feasible and reflects intratumoral heterogeneity.J Canc. 2016; 7: 1907-1914Crossref PubMed Scopus (58) Google Scholar, 42Jiao J. Niu W. Wang Y. Baggerly K. Ye Y. Wu X. et al.Prevalence of aflatoxin-associated TP53R249S mutation in hepatocellular carcinoma in hispanics in south Texas.Canc Prev Res (Phila). 2018; 11: 103-112Crossref PubMed Google Scholar, 43Liao W. Yang H. Xu H. Wang Y. Ge P. Ren J. et al.Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing.Oncotarget. 2016; 7: 40481-40490Crossref PubMed Scopus (68) Google Scholar, 44Marchio A. Amougou Atsama M. Béré A. Komas N.P. Noah Noah D. Atangana P.J.A. et al.Droplet digital PCR detects high rate of TP53 R249S mutants in cell-free DNA of middle African patients with hepatocellular carcinoma.Clin Exp Med. 2018; 18: 421-431Crossref PubMed Scopus (16) Google Scholar which reflect the molecular heterogeneity of a cancer that may be comprised of different tumour clones and metastases. This non-invasive approach involving cfDNA/ctDNA sampling in liquid biopsy is of great interest as it overcomes the limitation of traditional tissue biopsy and temporally reflects the clonal evolution in real time. Potential clinical utilities of cfDNA/ctDNA have been and are being investigated for the detection of HCC,45Huang Z.H. Hu Y. Hua D. Wu Y.Y. Song M.X. Cheng Z.H. Quantitative analysis of multiple methylated genes in plasma for the diagnosis and prognosis of hepatocellular carcinoma.Exp Mol Pathol. 2011; 91: 702-707Crossref PubMed Scopus (78) Google Scholar, 46Lu C.Y. Chen S.Y. Peng H.L. Kan P.Y. Chang W.C. Yen C.J. Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma.Oncotarget. 2017; 8: 6406-6418Crossref PubMed Scopus (23) Google Scholar, 47Yeo W. Wong N. Wong W.L. Lai P.B. Zhong S. Johnson P.J. High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma.Liver Int. 2005; 25: 266-272Crossref PubMed Scopus (88) Google Scholar, 48Zhang Y.J. Wu H.C. Shen J. Ahsan H. Tsai W.Y. Yang H.I. et al.Predicting hepatocellular carcinoma by detection of aberrant promoter methylation in serum DNA.Clin Canc Res. 2007; 13: 2378-2384Crossref PubMed Scopus (154) Google Scholar disease monitoring,49Cai Z.X. Chen G. Zeng Y.Y. Dong X.Q. Lin M.J. Huang X.H. et al.Circulating tumor DNA profiling reveals clonal evolution and real-time disease progression in advanced hepatocellular carcinoma.Int J Canc. 2017; 141: 977-985Crossref PubMed Scopus (49) Google Scholar, 50Ikeda S. Tsigelny I.F. Skjevik Å A. Kono Y. Mendler M. Kuo A. et al.Next-generation sequencing of circulating tumor DNA reveals frequent alterations in advanced hepatocellular carcinoma.Oncologist. 2018; 23: 586-593Crossref PubMed Scopus (38) Google Scholar, 51Wong I.H.N. Zhang J. Lai P.B.S. Lau W.Y. Dennis Lo Y.M. Quantitative analysis of tumor-derived methylated <strong><em>p16INK4a</em></strong> sequences in plasma, serum, and blood cells of hepatocellular carcinoma patients.Clin Canc Res. 2003; 9: 1047-1052PubMed Google Scholar and prognostication.[41]Huang A. Zhang X. Zhou S.L. Cao Y. Huang X.W. Fan J. et al.Detecting circulating tumor DNA in hepatocellular carcinoma patients using droplet digital PCR is feasible and reflects intratumoral heterogeneity.J Canc. 2016; 7: 1907-1914Crossref PubMed Scopus (58) Google Scholar,[43]Liao W. Yang H. Xu H. Wang Y. Ge P. Ren J. et al.Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing.Oncotarget. 2016; 7: 40481-40490Crossref PubMed Scopus (68) Google Scholar,[52]Ren N. Qin L.X. Tu H. Liu Y.K. Zhang B.H. Tang Z.Y. The prognostic value of circulating plasma DNA level and its allelic imbalance on chromosome 8p in patients with hepatocellular carcinoma.J Canc Res Clin Oncol. 2006; 132: 399-407Crossref PubMed Scopus (53) Google Scholar CtDNA targets must be detected among the background of total cfDNA. Given the short half-life (of between 16 mins and 2.5 h[53]Diehl F. Schmidt K. Choti M.A. Romans K. Goodman S. Li M. et al.Circulating mutant DNA to assess tumor dynamics.Nat Med. 2008; 14: 985-990Crossref PubMed Scopus (1620) Google Scholar) and low abundance of ctDNA, it is important to select the right sample collection tube and optimal processing methods to ensure successful DNA isolation. The concentration of cfDNA has been shown to be about 20-fold higher in serum than in matched plasma samples, predominantly as a result of the clotting process in the collection tube.[54]Lee T.H. Montalvo L. Chrebtow V. Busch M.P. Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma.Transfusion. 2001; 41: 276-282Crossref PubMed Scopus (234) Google Scholar Thus, plasma is the preferred biological sample. During handling and processing of whole blood into plasma, lysis of leukocytes can cause enormous contamination of plasma with genomic DNA, reducing if not eliminating, resolution for ctDNA targets. CtDNA is most commonly extracted from peripheral blood plasma; in contrast, processing of whole blood to serum results in shearing and lysis of leukocytes in the clot matrix. DNAases in circulation or sampled whole blood can cause potential loss of global cfDNA from the time of collection to processing to storage to analysis. Specialised tubes such as LBguard (Biomatrica, San Diego CA), Streck (La Vista NE) or Cell-Free DNA Collection (Roche, Basel Switzerland) tubes contain proprietary cfDNA preservation and cell stabilisation buffers for better ctDNA yield and quality.[55]Browne C.D. Mattmann M.E. Wycoco M.J. Chen S.N. Ravichandran R. Desharnais J. et al.Abstract 2758: comparison of cell-free DNA blood collection tubes.Canc Res. 2017; 77 (2758-2758)Google Scholar The separation of plasma from whole blood requires a 2000 x g centrifugation. The recommended storage temperature is -80oC. In the last decade, more robust methods with high analytical sensitivity have been developed for ctDNA analysis. These include digital droplet PCR, BEAMing (Beads, Emulsion, Amplification, Magnetic) technology, quantitative allele-specific real-time target and signal amplification and the resulting TELQAS (target enrichment long-probe quantitative amplified signal).56Diehl F. Li M. He Y. Kinzler K.W. Vogelstein B. Dressman D. BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions.Nat Methods. 2006; 3: 551-559Crossref PubMed Scopus (349) Google Scholar, 57Imperiale T.F. Ransohoff D.F. Itzkowitz S.H. Levin T.R. Lavin P. Lidgard G.P. et al.Multitarget stool DNA testing for colorectal-cancer screening.N Engl J Med. 2014; 370: 1287-1297Crossref PubMed Scopus (876) Google Scholar, 58Taly V. Pekin D. Benhaim L. Kotsopoulos S.K. Le Corre D. Li X. et al.Multiplex picodroplet digital PCR to detect KRAS mutations in circulating DNA from the plasma of colorectal cancer patients.Clin Chem. 2013; 59: 1722-1731Crossref PubMed Scopus (364) Google Scholar These methods allow for more targeted analyses of single nucleotide mutations or methylation changes for example. While the targeted PCR approach is lower cost and has very high sensitivity (mutation to wild-type ratios as low as 0.01%),[59]Chan K.C. Jiang P. Zheng Y.W. Liao G.J. Sun H. Wong J. et al.Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single-nucleotide variants, and tumoral heterogeneity by massively parallel sequencing.Clin Chem. 2013; 59: 211-224Crossref PubMed Scopus (372) Google Scholar small gene panels will miss mutations that are not selected. Much more costly, untargeted NGS approaches include whole genome sequencing (WGS), whole exome sequencing (WES) and whole genome bisulfite sequencing to screen the genome, exome or methylome for the discovery of known and new aberrations.[32]Newman A.M. Bratman S.V. To J. Wynne J.F. Eclov N.C. Modlin L.A. et al.An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage.Nat Med. 2014; 20: 548-554Crossref PubMed Scopus (1231) Google Scholar,[60]Kinde I. Wu J. Papadopoulos N. Kinzler K.W. Vogelstein B. Detection and quantification of rare mutations with massively parallel sequencing.Proc Natl Acad Sci U S A. 2011; 108: 9530-9535Crossref PubMed Scopus (727) Google Scholar A hybrid of these approaches uses NGS after targeted capture of hundreds or even thousands of known allelic or methylated variants. Early detection of HCC is critical as curative approaches are available when the tumour is small. Despite the current recommendations, standard ultrasound has several disadvantages including suboptimal performance (with sensitivity as low as 42% for lesions smaller than 1 cm), being operator dependent, and involving a cumbersome process for patients. Both CT and MRI perform better for the early detection of HCC. A systematic review including 20 studies reported a pooled sensitivity of 67.5% at 92.5% specificity for CT and 80.6% at 84.8% specificity for MRI.[61]Colli A. Fraquelli M. Casazza G. Massironi S. Colucci A. Conte D. et al.Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review.Am J Gastroenterol. 2006; 101: 513-523Crossref PubMed Scopus (399) Google Scholar For lesions greater than 2 cm, these imaging modalities showed great sensitivity and specificity. However, for small tumours and those that lack arterial-phase hyper-enhancement, which may be up to 40% of HCC, these imaging modalities are limiting in diagnosing HCC. For HCC ≤1 cm in size, detection rates can be as low as 34% and 10% for MRI and CT, respectively.[62]Choi J.Y. Lee J.M. Sirlin C.B. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects.Radiology. 2014; 272: 635-654Crossref PubMed Scopus (257) Google Scholar Other disadvantages of these tests include cost, access and radiation exposure. Thus, there is a clear need for non-invasive biomarkers that can identify early disease, ideally those patients with lesions <2 cm, and thereby minimise morbidity and mortality associated wi" @default.
• W3161243576 created "2021-05-24" @default.
• W3161243576 creator A5017521990 @default.
• W3161243576 creator A5038949267 @default.
• W3161243576 creator A5041256351 @default.
• W3161243576 date "2021-08-01" @default.
• W3161243576 modified "2023-10-11" @default.
• W3161243576 title "Using cell-free DNA for HCC surveillance and prognosis" @default.
• W3161243576 cites W1722699910 @default.
• W3161243576 cites W1913581775 @default.
• W3161243576 cites W1926072517 @default.
• W3161243576 cites W1971837077 @default.
• W3161243576 cites W1976892534 @default.
• W3161243576 cites W1983466841 @default.
• W3161243576 cites W1985444222 @default.
• W3161243576 cites W1991472738 @default.
• W3161243576 cites W1994306447 @default.
• W3161243576 cites W1994564728 @default.
• W3161243576 cites W2002960320 @default.
• W3161243576 cites W2004915826 @default.
• W3161243576 cites W2005655114 @default.
• W3161243576 cites W2009026548 @default.
• W3161243576 cites W2021299297 @default.
• W3161243576 cites W2025890159 @default.
• W3161243576 cites W2027735722 @default.
• W3161243576 cites W2029197798 @default.
• W3161243576 cites W2046509449 @default.
• W3161243576 cites W2048014608 @default.
• W3161243576 cites W2052099831 @default.
• W3161243576 cites W2057848194 @default.
• W3161243576 cites W2068093256 @default.
• W3161243576 cites W2069129640 @default.
• W3161243576 cites W2074137258 @default.
• W3161243576 cites W2077852082 @default.
• W3161243576 cites W2079345276 @default.
• W3161243576 cites W2084952307 @default.
• W3161243576 cites W2089470652 @default.
• W3161243576 cites W2094523641 @default.
• W3161243576 cites W2096837288 @default.
• W3161243576 cites W2099828433 @default.
• W3161243576 cites W2101887942 @default.
• W3161243576 cites W2115556288 @default.
• W3161243576 cites W2122231541 @default.
• W3161243576 cites W2138713106 @default.
• W3161243576 cites W2150027485 @default.
• W3161243576 cites W2152241467 @default.
• W3161243576 cites W2160756341 @default.
• W3161243576 cites W2239118478 @default.
• W3161243576 cites W2277004004 @default.
• W3161243576 cites W2315027248 @default.
• W3161243576 cites W2324757592 @default.
• W3161243576 cites W2412644869 @default.
• W3161243576 cites W2479773785 @default.
• W3161243576 cites W2552432336 @default.
• W3161243576 cites W2560499218 @default.
• W3161243576 cites W2561038004 @default.
• W3161243576 cites W2595761631 @default.
• W3161243576 cites W2598108680 @default.
• W3161243576 cites W2606367731 @default.
• W3161243576 cites W2618056026 @default.
• W3161243576 cites W2740053081 @default.
• W3161243576 cites W2764195238 @default.
• W3161243576 cites W2774536919 @default.
• W3161243576 cites W2783674487 @default.
• W3161243576 cites W2786099441 @default.
• W3161243576 cites W2787358630 @default.
• W3161243576 cites W2787984882 @default.
• W3161243576 cites W2790720112 @default.
• W3161243576 cites W2793971888 @default.
• W3161243576 cites W2794450296 @default.
• W3161243576 cites W2796067155 @default.
• W3161243576 cites W2800639499 @default.
• W3161243576 cites W2805592007 @default.
• W3161243576 cites W2809889937 @default.
• W3161243576 cites W2900295924 @default.
• W3161243576 cites W2908573150 @default.
• W3161243576 cites W2922467660 @default.
• W3161243576 cites W2944104549 @default.
• W3161243576 cites W2948870906 @default.
• W3161243576 cites W2952804432 @default.
• W3161243576 cites W2953533385 @default.
• W3161243576 cites W2964930572 @default.
• W3161243576 cites W2979099750 @default.
• W3161243576 cites W2997328224 @default.
• W3161243576 cites W3013924915 @default.
• W3161243576 cites W3020301997 @default.
• W3161243576 cites W3025022288 @default.
• W3161243576 cites W3029117824 @default.
• W3161243576 cites W3030573318 @default.
• W3161243576 cites W3031176267 @default.
• W3161243576 cites W3033879864 @default.
• W3161243576 cites W3082105590 @default.
• W3161243576 cites W3090413519 @default.
• W3161243576 cites W3094435218 @default.
• W3161243576 cites W3134082987 @default.
• W3161243576 cites W4235642752 @default.
• W3161243576 cites W4245403358 @default.
• W3161243576 cites W4250584784 @default.

• next