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.

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 Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy

2019 ◽  
Vol 116 (13) ◽  
pp. 6308-6312 ◽  
Author(s):  
Chunfeng Qu ◽  
Yuting Wang ◽  
Pei Wang ◽  
Kun Chen ◽  
Minjie Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Elevated Serum ◽  
Normal Liver ◽  
Protein Markers ◽  
Liquid Biopsies ◽  
B Virus ◽  
Asymptomatic Individuals

Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6–8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.

scholarly journals Current status of ctDNA in precision oncology for hepatocellular carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Yan Li ◽  
Yuanyuan Zheng ◽  
Liwei Wu ◽  
Jingjing Li ◽  
Jie Ji ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Diagnostic Technique ◽  
Response Assessment ◽  
Selection Response ◽  
Circulating Tumor Dna ◽  
Current Status ◽  
Precision Oncology ◽  
Tumor Biopsy ◽  
Non Invasive

AbstractThe conventional method used to obtain a tumor biopsy for hepatocellular carcinoma (HCC) is invasive and does not evaluate dynamic cancer progression or assess tumor heterogeneity. It is thus imperative to create a novel non-invasive diagnostic technique for improvement in cancer screening, diagnosis, treatment selection, response assessment, and predicting prognosis for HCC. Circulating tumor DNA (ctDNA) is a non-invasive liquid biopsy method that reveals cancer-specific genetic and epigenetic aberrations. Owing to the development of technology in next-generation sequencing and PCR-based assays, the detection and quantification of ctDNA have greatly improved. In this publication, we provide an overview of current technologies used to detect ctDNA, the ctDNA markers utilized, and recent advances regarding the multiple clinical applications in the field of precision medicine for HCC.

Liquid biopsy in the clinical management of hepatocellular carcinoma

Gut ◽  
2020 ◽  
Vol 69 (11) ◽  
pp. 2025-2034 ◽  
Author(s):  
Johann von Felden ◽  
Teresa Garcia-Lezana ◽  
Kornelius Schulze ◽  
Bojan Losic ◽  
Augusto Villanueva
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Response ◽  
Liquid Biopsy ◽  
Clinical Management ◽  
Early Stage ◽  
Personalised Medicine ◽  
Precision Oncology ◽  
Early Hepatocellular Carcinoma ◽  
Populations At Risk ◽  
Circulating Tumour Dna

With increasing knowledge on molecular tumour information, precision oncology has revolutionised the medical field over the past years. Liquid biopsy entails the analysis of circulating tumour components, such as circulating tumour DNA, tumour cells or tumour-derived extracellular vesicles, and has thus come as a handy tool for personalised medicine in many cancer entities. Clinical applications under investigation include early cancer detection, prediction of treatment response and molecular monitoring of the disease, for example, to comprehend resistance patterns and clonal tumour evolution. In fact, several tests for blood-based mutation profiling are already commercially available and have entered the clinical field.In the context of hepatocellular carcinoma, where access to tissue specimens remains mostly limited to patients with early stage tumours, liquid biopsy approaches might be particularly helpful. A variety of translational liquid biopsy studies have been carried out to address clinical needs, such as early hepatocellular carcinoma detection and prediction of treatment response. To this regard, methylation profiling of circulating tumour DNA has evolved as a promising surveillance tool for early hepatocellular carcinoma detection in populations at risk, which might soon transform the way surveillance programmes are implemented. This review summarises recent developments in the liquid biopsy oncological space and, in more detail, the potential implications in the clinical management of hepatocellular carcinoma. It further outlines technical peculiarities across liquid biopsy technologies, which might be helpful for interpretation by non-experts.

MSI-H testing via hybrid capture based NGS sequencing of liquid biopsy samples.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 504-504
Author(s):  
Kyle Gowen ◽  
Travis A Clark ◽  
Jeffrey P. Gregg ◽  
Mandy Z. Greene ◽  
Annie Murphy ◽  
...  
Keyword(s):  
Cell Lines ◽  
Liquid Biopsy ◽  
Checkpoint Inhibitors ◽  
Clinical Care ◽  
Mononucleotide Repeat ◽  
Liquid Biopsies ◽  
Tumor Biopsy ◽  
Mixing Ratios ◽  
Patients With Cancer ◽  
Fda Approval

504 Background: Microsatellite instability (MSI) testing has become critically important in clinical cancer care of patients with cancer given the recent pan-tumor FDA approval of pembrolizumab for use in patients with MSI-High (MSI-H) tumors. We previously demonstrated the robustness of a novel proprietary algorithm for determination of MSI status via NGS from solid tumor biopsy specimens (J Clin Oncol 34, 2016 (suppl; abstr 1523)). Traditional MSI tests such as PCR or IHC are impractical for pan-tumor adoption, as MSI-H prevalence outside of gastrointestinal and endometrial cancers is usually < 1%. NGS-based ctDNA profiling provides an opportunity for both MSI and actionable alteration testing in patients in whom tissue-based biopsy is not available. Methods: Genomic DNA (gDNA) from five previously characterized MSI-H cell lines: (DLD1, 22Rv1, LNCap, RL952, CL188), and one MSS cell line (SCC9) was enzymatically-fragmented to simulate ctDNA and titrated to various dilution levels with DNA from a healthy hapmap subject (NA12878). Samples were screened with a 70-gene panel, FoundationOne Liquid, that includes 180 mononucleotide repeat sequences (8-26bp long in the human reference genome). Length variability in the 180 repeat loci was utilized to generate an overall MSI score via principal components analysis. The NGS based MSI algorithm was applied to all the samples. Results: Assessment of these six cell lines, targeting five dilution levels confirmed by SNP mixing ratios, show that our NGS based MSI test for liquid biopsies has 96% sensitivity at > 2% tumor fraction with 100% PPV. The regression intercept of the MSI-H dilution samples with the pre-established MSI-H calling threshold shows our method has a LOD of 1.03% tumor fraction. MSI-H prevalence data from liquid biopsies of gastrointestinal tumors obtained during clinical care will also be presented. Conclusions: These data demonstrate the feasibility of using NGS-based liquid biopsy assays for MSI testing. This ctDNA-based approach will allow for increased access to checkpoint inhibitors in a pan-tumor setting, which would be especially relevant for cancers where routine MSI testing is impractical or when tissue is not available.

scholarly journals The Predictive Value of Vessels Encapsulating Tumor Clusters in Treatment Optimization for Recurrent Early-Stage Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zhi-Yuan Chen ◽  
Zhi-Xing Guo ◽  
Liang-He Lu ◽  
Jie Mei ◽  
Wen-Ping Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Predictive Value ◽  
Early Stage ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Survival Outcomes ◽  
Treatment Optimization ◽  
Initial Hepatectomy ◽  
Significant Difference

Abstract Background. The vessels encapsulating tumor clusters (VETC) pattern is an effective predictor of survival in patients with hepatocellular carcinoma (HCC) after resection. The predictive value of VETC in recurrent early-stage HCC remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). Methods. From December 2005 to December 2016, 138 patients who underwent RHR and 188 patients who underwent RFA were enrolled. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of treatment for patients with or without the VETC pattern was investigated. Results. Among VETC-positive HCC patients, 50 patients underwent RHR, and 69 patients underwent RFA; among VETC-negative HCC patients, 88 patients underwent RHR, and 119 patients underwent RFA. There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group had a longer median DFS time compared to those in the RFA group (15.0 vs 5.0 months, P=0.001). Similarly, the patients in the RHR group had a longer median OS time compared to those in the RFA group (39.5 vs 19 months, P=0.001). In the VETC-negative cohort, there was no significant difference in DFS and OS rates between the RHR and RFA groups (P>0.05).Conclusions. The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.

scholarly journals The landscape of gene fusions in hepatocellular carcinoma

2016 ◽  
Author(s):  
Chengpei Zhu ◽  
Yanling Lv ◽  
Liangcai Wu ◽  
Jinxia Guan ◽  
Xue Bai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Gene Fusion ◽  
Early Stage ◽  
Pcr Analysis ◽  
Gene Fusions ◽  
Fusion Genes ◽  
Rna Seq ◽  
Rt Pcr ◽  
Critical Function

AbstractMost hepatocellular carcinoma (HCC) patients are diagnosed at advanced stages and suffer limited treatment options. Challenges in early stage diagnosis may be due to the genetic complexity of HCC. Gene fusion plays a critical function in tumorigenesis and cancer progression in multiple cancers, yet the identities of fusion genes as potential diagnostic markers in HCC have not been investigated.Paired-end RNA sequencing was performed on noncancerous and cancerous lesions in two representative HBV-HCC patients. Potential fusion genes were identified by STAR-Fusion in STAR software and validated by four publicly available RNA-seq datasets. Fourteen pairs of frozen HBV-related HCC samples and adjacent non-tumor liver tissues were examined by RT-PCR analysis for gene fusion expression.We identified 2,354 different gene fusions in the two HBV-HCC patients. Validation analysis against the four RNA-seq datasets revealed only 1.8% (43/2,354) as recurrent fusions that were supported by public datasets. Comparison with four fusion databases demonstrated that three (HLA-DPB2-HLA-DRB1, CDH23-HLA-DPB1, and C15orf57-CBX3) out of 43 recurrent gene fusions were annotated as disease-related fusion events. Nineteen were novel recurrent fusions not previously annotated to diseases, including DCUN1D3-GSG1L and SERPINA5-SERPINA9. RT-PCR and Sanger sequencing of 14 pairs of HBV-related HCC samples confirmed expression of six of the new fusions, including RP11-476K15.1-CTD-2015H3.2.Our study provides new insights into gene fusions in HCC and could contribute to the development of anti-HCC therapy. RP11–476K15.1-CTD–2015H3.2 may serve as a new therapeutic biomarker in HCC.

scholarly journals Exosomal Non Coding RNA in LIQUID Biopsies as a Promising Biomarker for Colorectal Cancer

2020 ◽  
Vol 21 (4) ◽  
pp. 1398 ◽  
Author(s):  
Amro Baassiri ◽  
Farah Nassar ◽  
Deborah Mukherji ◽  
Ali Shamseddine ◽  
Rihab Nasr ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Sensitivity And Specificity ◽  
Liquid Biopsy ◽  
Early Stage ◽  
Noncoding Rnas ◽  
Predictive Biomarkers ◽  
Carbohydrate Antigen ◽  
Combination Regimen ◽  
Liquid Biopsies ◽  
Diagnostic Potential

Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific and could serve as predictive biomarkers for the most common chemotherapeutic drug and combination regimen in CRC, which are 5-FU and FOLFOX, respectively. Therefore, in this review, we focus on the role of these exosomal noncoding RNAs as diagnostic, prognostic, and predictive biomarkers. In addition, we discuss the advantages and challenges of exosomes as a liquid biopsy target.

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