scholarly journals Clinical Application Value of Circulating Cell-free DNA in Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuyuan Zhang ◽  
Zaoqu Liu ◽  
Kun Ji ◽  
Xin Li ◽  
Caihong Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liquid Biopsy ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Predictive Biomarker ◽  
Intrahepatic Metastasis ◽  
Genetic Profile ◽  
Cell Free Dna ◽  
Free Dna ◽  
Systemic Treatments

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.

scholarly journals Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Qing Yin ◽  
Chun-Hui Yuan ◽  
Zhen Qu ◽  
Qing Guan ◽  
Hao Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Liquid Biopsy ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Prognostic Significance ◽  
Liquid Biopsies ◽  
Tumor Biopsy ◽  
Diagnostic Strategies ◽  
Systemic Treatments

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of “liquid biopsy” have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. “Liquid biopsies” represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of “liquid biopsy” as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients.

Longitudinal monitoring of cell-free DNA to predict for transarterial chemo-embolization failure in hepatocellular carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14544-e14544
Author(s):  
Joanne Evans ◽  
Caroline Ward ◽  
Madhava Pai ◽  
Rohini Sharma
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
High Sensitivity ◽  
Cost Effective ◽  
Standard Of Care ◽  
Intermediate Stage ◽  
Cell Free Dna ◽  
Early Stage Disease ◽  
Free Dna ◽  
Synthetic Function

e14544 Background: Transarterial chemo-embolization (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma (HCC) with adequate synthetic function, and as bridging treatment in early stage disease. Survival outcomes are heterogeneous, and improved biomarkers are needed for detection of early relapse. Current practice relies on monitoring of alpha-foetoprotein (AFP) and serial imaging. Circulating cell-free DNA (cfDNA) is a compelling emergent biomarker. Here, we describe the first study of cfDNA as prognostic biomarker in HCC following TACE. Methods: 34 patients treated with TACE (2012-2018) who had full demographic information and longitudinal stored plasma available were identified. Samples were retrieved and cfDNA extracted using the QIAamp Circulating Nucleic Acid Kit. cfDNA yields were quantified by high-sensitivity Qubit analysis. Results: 74% of patients were male, 66% had Childs Pugh A disease, and 56% of patients secreted AFP ( > 10ng/mL). Aetiologies of liver diseases were varied: viral hepatitis (44%), alcoholic or non-alcoholic steatohepatitis/cirrhosis (29%), hereditary or auto-immune (12%), and unexplained (15%). 79% of patients saw a fall in cfDNA titre following TACE. Where no reduction was seen, patients had a poorer median overall survival than those who did: 20 months (range 5.13 – 66.7 months) compared to 37 months (9.9 – 79.3 months). Of note, 44% of patients were AFP non-secretors. Here, cfDNA had a clear advantage in disease monitoring, with mean cfDNA titres in this group falling post treatment: from 1605.1 (range 185.9 – 6830) ng/mL to 693.7 (range undetectable - 2300) ng/mL and rising again with subsequent progression (mean of 1329.2 - range 616 – 3341 - ng/mL). Conclusions: These findings support a cost-effective monitoring role for plasma cfDNA analysis following treatment with TACE, with an added advantage in AFP non-secretors. Prospective validation is suggested to fully assess clinical utility.

scholarly journals Urine as a non-invasive alternative to blood for germline and somatic mutation detection in hepatocellular carcinoma

2021 ◽  
Author(s):  
Amy K. Kim ◽  
Selena Y. Lin ◽  
Surbhi Jain ◽  
Yixiao Cui ◽  
Terence Gade ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Somatic Mutation ◽  
Liquid Biopsy ◽  
Mononuclear Cells ◽  
Cell Free Dna ◽  
Genome Coverage ◽  
Non Invasive ◽  
Free Dna ◽  
Genotype Information ◽  
Targeted Ngs

AbstractCell-free DNA (cfDNA) from blood has become a promising analyte for cancer genetic liquid biopsy. Urinary cfDNA has been shown to contain mutations associated with non-genitourologic cancers including hepatocellular carcinoma (HCC). In this study, we evaluate urine as a noninvasive alternative to blood-based liquid biopsy in both germline and circulating tumor DNA (ctDNA) genotyping in HCC. Using quantitative PCR (qPCR), whole-genome sequencing (WGS), and targeted NGS, DNA isolated from blood or urine of patients with HCC was analyzed for overall genome coverage, HCC hotspot coverage, and germline or somatic mutation concordance. Targeted NGS of plasma and urine cfDNA was also performed for detection of somatic variants. We found urine cfDNA, similar to plasma cfDNA, showed a major mononucleosomal species of 150-180 bp in both healthy individuals and patients with HCC. By WGS, overall genome coverage breadth was similar between urine and plasma cfDNA, with higher fraction of covered cancer-associated mutation hotspots in urine cfDNA. qPCR analyses of HCC-associated mutations (TP53, CTNNB1, and TERT) in 101 patients with HCC revealed 78% overall concordance between plasma and urine. Targeted NGS of HCC-associated gene regions in additional 15 HCC patients showed a 97% overall position-level concordance between plasma and urine cfDNA. Collectively, urine DNA can potentially be used as a completely noninvasive liquid biopsy for HCC.Significance StatementHepatocellular carcinoma (HCC) is the most common liver cancer worldwide and the fastest growing gastrointestinal cancer in the U.S. Cell-free DNA (cfDNA) which originates from various cells undergoing apoptosis or necrosis including tumor cells, is present in all body fluids levels including urine. Urinary cfDNA isolated from patients with HCC showed a similar fragment size distribution, overall genome coverage, and comparable sensitivity for detecting HCC-associated variants compared to plasma cfDNA. Urine was also determined to be a reliable source of germline genotype information, similar to peripheral blood mononuclear cells in blood-based liquid biopsies. Urine cfDNA can be used as a completely non-invasive liquid biopsy in HCC.

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 ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Molecular Targeted Therapy ◽  
Predictive Biomarker ◽  
Post Treatment ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Circulating Cell-Free DNA Combined to Magnetic Resonance Imaging for Early Detection of HCC in Patients with Liver Cirrhosis

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 521
Author(s):  
Marianna Alunni-Fabbroni ◽  
Sabine Weber ◽  
Osman Öcal ◽  
Max Seidensticker ◽  
Julia Mayerle ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Hepatocellular Cancer ◽  
Current Standard ◽  
Mri Findings ◽  
Cell Free Dna ◽  
Free Dna ◽  
Increased Risk ◽  
Circulating Cell Free Dna

Liquid biopsy based on circulating cell-free DNA (cfDNA) is a promising non-invasive tool for the prognosis of hepatocellular cancer (HCC). In this exploratory study we investigated whether cfDNA and gene variants associated with HCC may be found in patients with liver cirrhosis (LC) and thus identify those at an increased risk for HCC. A cohort of 40 LC patients with no suspect neoplastic lesions was included in this study. Next generation sequencing (NGS) of cfDNA isolated from plasma was performed on a panel of 597 selected genes. Images of the patients who underwent MRI with hepatospecific contrast media during the study period were retrospectively re-evaluated (imaging was not part of the prospective study). cfDNA was detected in the plasma of 36 patients with LC. NGS-based analyses identified 20 variants in different combinations. Re-evaluation of the MRI images that were available for a proportion of the patients (n = 27) confirmed the absence of lesions in 8 cases carrying cfDNA without variants. In 6 of 19 patients with identified variants and MRI images available, MRI revealed a precursor lesion compatible with HCC and new lesions were discovered at follow-up in two patients. These precursor lesions were amenable for curative treatments. Mutation analysis revealed selective HCC related gene mutations in a subset of patients with LC, raising the suspect that these patients were at an increased risk for HCC development. MRI findings confirmed suspect nodular lesions of early stage HCC not detected with current standard screening procedures, which were only seen in patients carrying cfDNA variants. This opens a perspective for an HCC screening strategy combining both liquid biopsy and MRI in patients with LC.

Cell free DNA as an evolving liquid biopsy biomarker for initial diagnosis and therapeutic nursing in Cancer- An evolving aspect in Medical Biotechnology

2020 ◽  
Vol 21 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Tumor Cells ◽  
Liquid Biopsy ◽  
Cancer Metastasis ◽  
Nuclear Dna ◽  
Fragment Size ◽  
Body Fluids ◽  
Response To Therapy ◽  
Significant Information ◽  
Cell Free Dna ◽  
Free Dna

: Cell-free DNA (cfDNA) is present in numerous body fluids in addition to initiates generally from blood cells. It is undoubtedly the utmost promising tool among all components of liquid biopsy. Liquid biopsy is a specialized method investigating the nonsolid biological tissue by revealing of circulating cells, cell free DNA etc. that enter body fluids. Since, cancer cells disengage from compact tumors circulate in peripheral blood, evaluating blood of cancer patients holds the opportunities for capture and molecular level analysis of various tumor-derived constituents. Cell free DNA samples can deliver a significant perceptions into oncology, for instance tumor heterogeneity, instantaneous tumor development, response to therapy and treatment, comprising immunotherapy and mechanisms of cancer metastasis. Malignant growth at any phase can outhouse tumor cells in addition to fragments of neoplasticity causing DNA into circulatory system giving noble sign of mutation in the tumor at sampling time. Liquid biopsy distinguishes diverse blood based evolving biomarkers comprising circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or cfDNA, circulating RNA (cfRNA) and exosomes. Cell free DNA are little DNA fragments found circulating in plasma or serum, just as other fluids present in our body. Cell free DNA involves primarily double stranded nuclear DNA and mitochondrial DNA, present both on a surface level and in the lumen of vesicles. The probable origins of the tumor-inferred portion of cfDNA are apoptosis or tumor necrosis, lysis of CTCs or release of DNA from the tumor cells into circulation. The evolution of innovations, refinement and improvement in therapeutics for determination of cfDNA fragment size and its distribution provide significant information related with pathological conditions of the cell, thus emerging as promising indicator for clinical output in medical biotechnology.

Genomic variations in plasma cell free DNA differentiate early stage lung cancers from normal controls

Lung Cancer ◽  
2015 ◽  
Vol 90 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Shu Xia ◽  
Chiang-Ching Huang ◽  
Min Le ◽  
Rachel Dittmar ◽  
Meijun Du ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Early Stage ◽  
Cell Free Dna ◽  
Lung Cancers ◽  
Genomic Variations ◽  
Free Dna ◽  
Normal Controls
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