Plasma levels of methylated septin 9 are capable of detecting hepatocellular carcinoma and hepatic cirrhosis

He, Na; Feng, Guohua; Zhang, Chunyan; Wu, Fangxiong; Zhang, Ting; Yang, Yongqin

doi:10.3892/mmr.2020.11356

Cited by 6 publications

(12 citation statements)

References 31 publications

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“…1 ). Eventually, the full text of 59 eligible articles (60 studies) was incorporated into this meta-analysis ( Huang et al, 2003 ; Wang et al, 2021 ; Wong et al, 2000 ; Wong et al, 2003 ; Chu et al, 2004 ; Lin et al, 2005 ; Yeo et al, 2005 ; Iizuka et al, 2006 ; Ren et al, 2006 ; Wang et al, 2006 ; Zhang et al, 2007 ; Chan et al, 2008 ; Chang et al, 2008 ; Igetei et al, 2008 ; Ahmed et al, 2010 ; El-Shazly et al, 2010 ; Hu et al, 2010 ; Huang et al, 2011 ; Iizuka et al, 2011 ; Yang et al, 2011 ; Chen et al, 2012 ; Huang et al, 2012 ; Mohamed et al, 2012 ; Chen et al, 2013 ; Sun et al, 2013 ; Zhang et al, 2013 ; Han et al, 2014 ; Huang et al, 2014 ; Ji et al, 2014 ; Kuo et al, 2014 ; Li et al, 2014 ; Yang et al, 2014 ; Dong et al, 2015 ; Huang et al, 2015 ; Ramadan et al, 2015 ; Teng et al, 2016 ; Dong et al, 2017 ; Hu et al, 2017 ; Mansour et al, 2017 ; Tian et al, 2017 ; Wu et al, 2017 ; Gai et al, 2018 ; Li et al, 2018 ; Oussalah et al, 2018 ; Wei et al, 2018 ; Linlin et al, 2018 ; Bai et al, 2019 ; Kisiel et al, 2019 ; Marchio et al, 2019 ; Pasha, Mohamed & Radwan, 2019 ; El-Bendary et al, 2020 ; He et al, 2020 ; Kotoh et al, 2020 ; Li et al, 2020a …”

Section: Resultsunclassified

“…Table S1 summarizes the characteristics of all 59 papers ( n = 92). All the included studies included quantitative analysis to measure ctDNA concentration and single-gene methylation concentration ( n = 19) ( Wang et al, 2021 ; Iizuka et al, 2006 ; Ren et al, 2006 ; Chan et al, 2008 ; El-Shazly et al, 2010 ; Iizuka et al, 2011 ; Yang et al, 2011 ; Chen et al, 2012 ; Huang et al, 2012 ; Mohamed et al, 2012 ; Chen et al, 2013 ; He et al, 2020 ; Kotoh et al, 2020 ; Li et al, 2020a ; Xie et al, 2021 ; Mansour et al, 2017 ; Gai et al, 2018 ; Linlin et al, 2018 ; El-Bendary et al, 2020 ) and qualitative analysis of tumor-specific ctDNA single gene-mutation and methylation ( n = 40) ( Wong et al, 2000 ; Wong et al, 2003 ; Chu et al, 2004 ; Lin et al, 2005 ; Yeo et al, 2005 ; Wang et al, 2006 ; Zhang et al, 2007 ; Chang et al, 2008 ; Igetei et al, 2008 ; Ahmed et al, 2010 ; Hu et al, 2010 ; Huang et al, 2011 ; Sun et al, 2013 ; Zhang et al, 2013 ; Han et al, 2014 ; Huang et al, 2014 ; Ji et al, 2014 ; Kuo et al, 2014 ; Li et al, 2014 ; Yang et al, 2014 ; Dong et al, 2015 ; Huang et al, 2015 ; Ramadan et al, 2015 ; Teng et al, 2016 ; Dong et al, 2017 ; Hu et al, 2017 ; Tian et al, 2017 ; Wu et al, 2017 ; Li et al, 2018 ; Oussalah et al, 2018 ; Wei et al, 2018 ;…”

Section: Resultsmentioning

confidence: 99%

“…Publications were judged as having high risk in one field, which was consider as having an overall high risk of bias. However, two studies were excluded due to the high risk of bias in patient selection and reference concerns ( Lleonart et al, 2005 ; Marchio et al, 2018 ) , and four articles ( Chan et al, 2008 ; Ahmed et al, 2010 ; Huang et al, 2012 ; Lewin et al, 2021 ) had a high risk of bias regarding patient selection and others had a risk of bias in index text ( He et al, 2020 ) or reference standards ( Huang et al, 2003 ). Additionally, due to missing information, the risk of bias could not be assessed for another 16 studies ( Yeo et al, 2005 ; Iizuka et al, 2006 ; Igetei et al, 2008 ; Chen et al, 2013 ; Li et al, 2014 ; Yang et al, 2014 ; Ramadan et al, 2015 ; Dong et al, 2017 ; Mansour et al, 2017 ; Li et al, 2018 ; Wei et al, 2018 ; Linlin et al, 2018 ; Bai et al, 2019 ; Marchio et al, 2019 ; El-Bendary et al, 2020 ; Xie et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

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Diagnostic performance of circulating tumor DNA as a minimally invasive biomarker for hepatocellular carcinoma: a systematic review and meta-analysis

2022

PeerJ

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Purpose This study aimed to assess the diagnostic performance of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC). Materials and Methods We enrolled all relevant studies published up to 5 January 2022. Three primary subgroups were investigated: qualitative or quantitative ctDNA analyses, combined alpha-fetoprotein (AFP), and ctDNA assay. In addition to the three primary subgroups, we also evaluated the diagnostic value of methylated SEPTIN9 (mSEPT9), which has been studied extensively in the diagnosis of hepatocellular carcinoma. After a search based on four primary databases, we used a bivariate linear mixed model to analyze the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). We also plotted hierarchical summary receiver operating characteristics (HSROC) and utilized lambda as well as the area under the curve (AUC) to create summary receiver operating characteristic (SROC) curves to estimate the diagnostic value of ctDNA. Results A total of 59 qualified articles with 9,766 subjects were incorporated into our meta-analysis. The integrated SEN, SPE, and DOR in the qualitative studies were 0.50 (95% CI [0.43–0.56]), 0.90 (95% CI [0.86–0.93]), and 8.72 (95% CI [6.18–12.32]), respectively, yielding an AUC of 0.78 and lambda of 1.93 (95% CI [1.56–2.33]). For quantitative studies, the corresponding values were 0.69 (95% CI [0.63–0.74]), 0.84 (95% CI [0.77–0.89]), 11.88 (95% CI [7.78–18.12]), 0.81, and 2.32 (95% CI [1.96–2.69]), respectively. Six studies were included to evaluate the SETP9 methylation, which yielded an AUC of 0.86, a SEN of 0.80 (95% CI [0.71–0.87]), and a SPE of 0.77 (95% CI [0.68–0.85]). Likewise, ctDNA concentration yielded an AUC of 0.73, with a SEN of 0.63 (95% CI [0.56–0.70]) and a SPE of 0.86 (95% CI [0.74–0.93]). AFP combined with ctDNA assay resulted in an AUC of 0.89, with a SEN of 0.82 (95% CI [0.77–0.86]) and a SPE of 0.84 (95% CI [0.76–0.90]). Conclusion This study shows that circulating tumor DNA, particularly mSEPT9, shows promising diagnostic potential in HCC; however, it is not enough to diagnose HCC independently, and ctDNA combined with conventional assays such as AFP can effectively improve diagnostic performance.

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Section: Resultsunclassified

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Diagnostic performance of circulating tumor DNA as a minimally invasive biomarker for hepatocellular carcinoma: a systematic review and meta-analysis

2022

PeerJ

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“…Other single methylated ctDNA biomarkers tested in case–control studies include genes encoding for Ras association domain family 1A ( RASSF1A ) [ 86 , 87 ], vimentin ( VIM ) [ 88 ], fibulin 1 ( FBLN1 ) [ 88 ], and tissue factor pathway inhibitor-2 (TFPI2) [ 98 ]. More recently, methylated septin 9 ( SEPT9 ) gene, the biomarker used in the first blood-based test commercialized for the early detection of colorectal carcinoma, has demonstrated high accuracy (area under the receiver operating curve, AURC, of 0.94) to diagnose HCC in two independent cohorts [ 94 ] and to predict long-term survival of HCC patients [ 95 ]. SEPT9 is a key regulator of cell division implicated in liver carcinogenesis [ 110 ], which is silenced by promoter hypermethylation not only in HCC [ 58 ] and colorectal cancer, but also in other tumors such as head and neck squamous cell carcinoma and breast cancer [ 111 , 112 ].…”

Section: Epigenetic Biomarkers In Liquid Biopsy: Methylated Ctdna mentioning

confidence: 99%

“…Moreover, the combination of these emerging epigenetic biomarkers with currently used serological markers can be envisioned to be used to improve HCC diagnosis, patient stratification, and evaluation of treatment response. In this regard, several studies have shown increased sensitivity when their identified epigenetic liquid biopsy biomarkers are combined with AFP determination [ 93 , 95 , 98 ]. The presence and levels of naïve viral RNA and DNA [ 119 ], its integration in cellular DNA, or even epigenetic modifications of viral sequences [ 84 ] along the hepatocarcinogenesis process could also be combined.…”

Section: Epigenetic Biomarkers In Liquid Biopsy: Methylated Ctdna mentioning

confidence: 99%

Epigenetic Biomarkers for the Diagnosis and Treatment of Liver Disease

Arechederra

Recalde

Gárate-Rascón

et al. 2021

Cancers

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Research in the last decades has demonstrated the relevance of epigenetics in controlling gene expression to maintain cell homeostasis, and the important role played by epigenome alterations in disease development. Moreover, the reversibility of epigenetic marks can be harnessed as a therapeutic strategy, and epigenetic marks can be used as diagnosis biomarkers. Epigenetic alterations in DNA methylation, histone post-translational modifications (PTMs), and non-coding RNA (ncRNA) expression have been associated with the process of hepatocarcinogenesis. Here, we summarize epigenetic alterations involved in the pathogenesis of chronic liver disease (CLD), particularly focusing on DNA methylation. We also discuss their utility as epigenetic biomarkers in liquid biopsy for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Finally, we discuss the potential of epigenetic therapeutic strategies for HCC treatment.

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Risk stratification and early detection biomarkers for precision HCC screening

et al. 2022

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Hepatocellular carcinoma (HCC) mortality remains high primarily due to late diagnosis as a consequence of failed early detection. Professional societies recommend semi-annual HCC screening in at-risk patients with chronic liver disease to increase the likelihood of curative treatment receipt and improve survival. However, recent dynamic shift of HCC etiologies from viral to metabolic liver diseases has significantly increased the potential target population for the screening, whereas annual incidence rate has become substantially lower. Thus, with the contemporary HCC etiologies, the traditional screening approach might not be practical and cost-effective. HCC screening consists of (i) definition of rational at-risk population, and subsequent (ii) repeated application of early detection tests to the population at regular intervals. The suboptimal performance of the currently available HCC screening tests highlights an urgent need for new modalities and strategies to improve early HCC detection. In this review, we overview recent developments of clinical, molecular, and imaging-based tools to address the current challenge, and discuss conceptual framework and approaches of their clinical translation and implementation. These encouraging progresses are expected to transform the current "one-size-fits-all" HCC screening into

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Plasma levels of methylated septin 9 are capable of detecting hepatocellular carcinoma and hepatic cirrhosis

Cited by 6 publications

References 31 publications

Diagnostic performance of circulating tumor DNA as a minimally invasive biomarker for hepatocellular carcinoma: a systematic review and meta-analysis

Diagnostic performance of circulating tumor DNA as a minimally invasive biomarker for hepatocellular carcinoma: a systematic review and meta-analysis

Epigenetic Biomarkers for the Diagnosis and Treatment of Liver Disease

Risk stratification and early detection biomarkers for precision HCC screening

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