Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma

2021 ◽  
Vol 56 (5) ◽  
pp. 456-469
Author(s):  
Takuma Nakatsuka ◽  
Hayato Nakagawa ◽  
Yuki Hayata ◽  
Taijiro Wake ◽  
Tomoharu Yamada ◽  
...  
2021 ◽  
Vol 8 ◽  
Author(s):  
Yuyuan Zhang ◽  
Zaoqu Liu ◽  
Kun Ji ◽  
Xin Li ◽  
Caihong Wang ◽  
...  

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and a leading cause of cancer-related deaths. Due to late diagnosis, early intrahepatic metastasis and nonresponse to systemic treatments, surgical resection and/or biopsy specimens remain the gold standard for disease staging, grading and clinical decision-making. Since only a small amount of tissue was obtained in a needle biopsy, the conventional tissue biopsy is unable to represent tumor heterogeneity in HCC. For this reason, it is imperative to find a new non-invasive and easily available diagnostic tool to detect HCC at an early stage and to monitor HCC recurrence. The past decade has witnessed considerable evolution in the development of liquid biopsy technologies with the emergence of next-generation sequencing. As a liquid biopsy approach, molecular analysis of cell-free DNA (cfDNA), characterized by noninvasiveness and real-time analysis, may accurately represent the tumor burden and comprehensively reflect genetic profile of HCC. Therefore, cfDNA may be used clinically as a predictive biomarker in early diagnosis, outcome assessment, and even molecular typing. In this review, we provide an update on the recent advances made in clinical applications of cfDNA in HCC.


Medicine ◽  
2015 ◽  
Vol 94 (14) ◽  
pp. e722 ◽  
Author(s):  
Wenjun Liao ◽  
Yilei Mao ◽  
Penglei Ge ◽  
Huayu Yang ◽  
Haifeng Xu ◽  
...  

BMC Cancer ◽  
2010 ◽  
Vol 10 (1) ◽  
Author(s):  
Winnie Yeo ◽  
Pei-Jer Chen ◽  
Junji Furuse ◽  
Kwang-Hyub Han ◽  
Chiun Hsu ◽  
...  

2018 ◽  
Vol 115 (46) ◽  
pp. E10925-E10933 ◽  
Author(s):  
Peiyong Jiang ◽  
Kun Sun ◽  
Yu K. Tong ◽  
Suk Hang Cheng ◽  
Timothy H. T. Cheng ◽  
...  

Circulating tumor-derived cell-free DNA (ctDNA) analysis offers an attractive noninvasive means for detection and monitoring of cancers. Evidence for the presence of cancer is dependent on the ability to detect features in the peripheral circulation that are deemed as cancer-associated. We explored approaches to improve the chance of detecting the presence of cancer based on sequence information present on ctDNA molecules. We developed an approach to detect the total pool of somatic mutations. We then investigated if there existed a class of ctDNA signature in the form of preferred plasma DNA end coordinates. Cell-free DNA fragmentation is a nonrandom process. Using plasma samples obtained from liver transplant recipients, we showed that liver contributed cell-free DNA molecules ended more frequently at certain genomic coordinates than the nonliver-derived molecules. The abundance of plasma DNA molecules with these liver-associated ends correlated with the liver DNA fractions in the plasma samples. Studying the DNA end characteristics in plasma of patients with hepatocellular carcinoma and chronic hepatitis B, we showed that there were millions of tumor-associated plasma DNA end coordinates in the genome. Abundance of plasma DNA molecules with tumor-associated DNA ends correlated with the tumor DNA fractions even in plasma samples of hepatocellular carcinoma patients that were subjected to shallow-depth sequencing analysis. Plasma DNA end coordinates may therefore serve as hallmarks of ctDNA that could be sampled readily and, hence, may improve the cost-effectiveness of liquid biopsy assessment.


2019 ◽  
Vol 7 (22) ◽  
pp. 650-650 ◽  
Author(s):  
Dong Wang ◽  
Xi Hu ◽  
Guo Long ◽  
Liang Xiao ◽  
Zhi-Ming Wang ◽  
...  

2015 ◽  
Vol 112 (11) ◽  
pp. E1317-E1325 ◽  
Author(s):  
Peiyong Jiang ◽  
Carol W. M. Chan ◽  
K. C. Allen Chan ◽  
Suk Hang Cheng ◽  
John Wong ◽  
...  

The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-levelz-score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.


2018 ◽  
Vol 18 (3) ◽  
pp. 421-431 ◽  
Author(s):  
Agnès Marchio ◽  
Marie Amougou Atsama ◽  
Aubin Béré ◽  
Narcisse-Patrice Komas ◽  
Dominique Noah Noah ◽  
...  

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