Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma

Xu, Rui; Wei, Wei; Krawczyk, Michał; Wang, Wen-Qiu; Luo, Hongyu; Flagg, Ken; Yi, Shaohua; Shi, William Y.; Quan, Qingli; Li, Kang; Zheng, Lianghong; Zhang, Heng; Caughey, Bennett Adam; Zhao, Qi; Hou, Jiayi; Zhang, Runze; Xu, Yanxin; Cai, Huimin; Li, Gen; Hou, Rui; Zhong, Zheng; Lin, Danni; Fu, Xin; Zhu, Jie; Duan, Yaou; Yu, Mei; Ying, Binwu; Zhang, Wengeng; Wang, Juan; Zhang, Edward; Zhang, Charlotte; Li, Oulan; Guo, Rong; Carter, Hannah; Zhu, Jian; Hao, Xiaoke; Zhang, Kang

doi:10.1038/nmat4997

Cited by 681 publications

(616 citation statements)

References 37 publications

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“…ctDNA may be quite low and therefore below the limit of detection, especially in earlystage and indolent tumors. The improvement of different technics such as digital PCR and sequencing technologies provide us an effective way for the discovery of additional ctDNA markers [91,92] .…”

Section: Cell-free Tumor Associated Dnamentioning

confidence: 99%

Performance of different biomarkers for the management of hepatocellular carcinoma

Rojas¹,

Sánchez‐Torrijos²,

Gil‐Gómez³

et al. 2018

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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second cause of cancer related death due to latent liver disease, late diagnosis and non-available therapeutic treatment. Liver biopsy is still the gold standard in order to know the molecular biology of the tumor, its behaviour and invasive characteristics. Conventional diagnosis methods for HCC detection include imaging and serological tests with low sensitivity and specificity. In this review, we focus on the potential utility of certain serum biomarkers and a new approach, "liquid biopsy", in the management of HCC patients.

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Section: Cell-free Tumor Associated Dnamentioning

confidence: 99%

Performance of different biomarkers for the management of hepatocellular carcinoma

Rojas¹,

Sánchez‐Torrijos²,

Gil‐Gómez³

et al. 2018

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“…In fact, DNA methylation abnormalities are one of the hallmarks of cancer and are associated with all aspects of cancer, from tumor initiation to cancer progression and metastasis (11–13). These nice properties inspired a number of recent approaches in using DNA methylation patterns for cancer diagnosis (14,15). Here, we aim to amplify aberrant cfDNA methylation signals at the resolution of single sequencing reads, therefore providing an ultra-sensitive detection of a tiny amount of tumor cfDNA even at a low sequencing coverage.…”

Section: Introductionmentioning

confidence: 95%

CancerDetector: ultrasensitive and non-invasive cancer detection at the resolution of individual reads using cell-free DNA methylation sequencing data

Kang

et al. 2018

Nucleic Acids Research

152

164

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The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such an approach is how to identify the tiny amount of tumor DNAs out of total cell-free DNAs in blood. Here we propose an ultrasensitive cancer detection method, termed ‘CancerDetector’, using the DNA methylation profiles of cell-free DNAs. The key of our method is to probabilistically model the joint methylation states of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. We evaluated CancerDetector on the simulated data, and showed a high concordance of the predicted and true tumor fraction. Testing CancerDetector on real plasma data demonstrated its high sensitivity and specificity in detecting tumor cfDNAs. In addition, the predicted tumor fraction showed great consistency with tumor size and survival outcome. Note that all of those testing were performed on sequencing data at low to medium coverage (1× to 10×). Therefore, CancerDetector holds the great potential to detect cancer early and cost-effectively.

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“…Although a high degree of methylation at multiple genes has been shown to play an important role in the process of HCC diagnosis, there is no recognized indicator confirmed in multiple centers. In addition, the combined detection of the methylation status of multiple genes may be an effective way to improve the diagnostic efficiency [94]. To evaluate the potential of ctDNA methylation markers for diagnosing and evaluating the prognosis of HCC, Xu RH et al [94] compared differential methylation profiles of HCC tissues and blood leukocytes in healthy individuals and identified a methylation marker panel that is enriched in HCC.…”

Section: Introductionmentioning

confidence: 99%

Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Han

et al. 2018

J Exp Clin Cancer Res

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Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, “liquid biopsy,” (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.

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Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma

Cited by 681 publications

References 37 publications

Performance of different biomarkers for the management of hepatocellular carcinoma

Performance of different biomarkers for the management of hepatocellular carcinoma

CancerDetector: ultrasensitive and non-invasive cancer detection at the resolution of individual reads using cell-free DNA methylation sequencing data

Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

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