Biomarker Development Using Liquid Biopsy in Hepatocellular Carcinoma

Grinspan, Lauren Tal; Villanueva, Augusto

doi:10.1055/s-0042-1748924

Cited by 10 publications

(3 citation statements)

References 123 publications

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“… 25 , 33 , 34 Alpha fetoprotein may emerge as a useful screening modality for HCC in post‐SVR patients and should be investigated for this purpose, both alone and in combination with current and novel imaging methods 35 and emerging serum biomarkers. 36 Given current technologies, patients without cirrhosis who do not meet AASLD criteria for HCC surveillance, which entails abdominal ultrasound every 6 months, might benefit from serial AFP measurement.…”

Section: Discussionmentioning

confidence: 99%

Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis

et al. 2023

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Background Successful treatment of hepatitis C reduces liver inflammation and fibrosis; however, patients remain at risk of developing hepatocellular carcinoma (HCC). Aims To identify risk factors for new‐onset HCC in patients cured of hepatitis C. Methods Imaging, histological, and clinical data on patients whose first HCC was diagnosed >12 months of post‐SVR were analyzed. Histology of 20 nontumor tissues was analyzed in a blinded manner using the Knodel/Ishak/HAI system for necroinflammation and fibrosis/cirrhosis stage and the Brunt system for steatosis/steatohepatitis. Factors associated with post‐SVR HCC were identified by comparison with HALT‐C participants who did not develop post‐SVR HCC. Results Hepatocellular carcinoma was diagnosed in 54 patients (45 M/9F), a median of 6 years of post‐SVR [interquartile range (IQR) =1.4‐10y] at a median age of 61 years (IQR, 59–67). Approximately one‐third lacked cirrhosis, and only 11% had steatosis on imaging. The majority (60%) had no steatosis/steatohepatitis in histopathology. The median HAI score was 3 (1.25–4), indicating mild necroinflammation. In a multivariable logistic regression model, post‐SVR HCC was positively associated with non‐Caucasian race (p = 0.03), smoking (p = 0.03), age > 60 years at HCC diagnosis (p = 0.03), albumin<3.5 g/dL (p = 0.02), AST/ALT>1 (p = 0.05), and platelets <100 × 103 cells/μL (p < 0.001). Alpha fetoprotein ≥4.75 ng/mL had 90% specificity and 71% sensitivity for HCC occurrence. Noncirrhotic patients had larger tumors (p = 0.002) and a higher prevalence of vascular invasion (p = 0.016) than cirrhotic patients. Conclusions One‐third of patients with post‐SVR HCC did not have liver cirrhosis; most had no steatosis/steatohepatitis. Hepatocellular carcinomas were more advanced in noncirrhotic patients. Results support AFP as a promising marker of post‐SVR HCC risk.

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Section: Discussionmentioning

confidence: 99%

Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis

et al. 2023

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“…A liquid biopsy involves capturing tumor information from the blood, reflecting the body's systemic tumor information. Compared with traditional needle biopsy, liquid biopsy has the advantages of non-invasiveness, repeated sampling, real-time "update feedback" of tumor burdens, overcoming tumor heterogeneity, and guiding personalized medicine [6]. The clinical application of liquid biopsy in the clinical diagnosis and treatment of tumors includes the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTC), circulating microribonucleic acid (miRNA), and exosomes [3,7,8].…”

Section: Introductionmentioning

confidence: 99%

Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer

Xin

2023

Diagnostics

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Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with low rates of early diagnosis and surgical resection. In recent years, with the rapid development of liquid biopsy technology, circulating tumor DNA (ctDNA) has emerged as a research hotspot in the field of precision medicine for liver cancer. Existing studies have demonstrated the suitability of ctDNA for combined detection with other liver cancer diagnostic markers, enabling a multi-index analysis. In recent years, a novel prediction model has been developed for early liver cancer screening based on ctDNA liquid biopsy, M2P-HCC (methylation, mutation, and protein-HCC), mainly incorporating methylation changes, gene mutations, and protein markers associated with liver cancer. Preliminary validation in the HCCscreenTM Investigational (HIT, ChiCTR1800020233) study, which focused on screening early liver cancer in communities with Hepatitis B surface antigen (HBsAg) positivity, yielded promising results with 100% sensitivity and 94% specificity. However, it remains uncertain whether M2P-HCC can be effectively applied in high-risk populations for Hepatitis B-associated liver cancer, warranting further research. Methods: Patients who were under long-term follow-up at the outpatient clinic of the Infectious Diseases Center of West China Hospital of Sichuan University from December 2020 to January 2023 were recruited in this prospective observational study and underwent the M2P-HCC test. The study population consisted of high-risk patients with Hepatitis B-related liver cancer who met the inclusion criteria. Patients with a history of previous malignancy, recent blood transfusion, autoimmune diseases, and human immunodeficiency virus (HIV) infection were excluded. Clinical data were collected at a baseline, and all patients underwent the M2P-HCC blood test. Based on the test results, they were categorized into positive, early-warning, and negative groups. Prospective cohort observation and regular follow-ups were performed for 6–8 months. Results: 313 patients met the inclusion criteria and were included in the study. After 6–8 months of follow-up, HCC occurred in 41(13.1%) participants. The M2P-HCC test demonstrated good predictive performance with an area under the curve (AUC) of 0.88 (95% CI: 0.81–0.95, p < 0.001) and a cutoff value of 83 points (sensitivity 82.9% and specificity 85.7%). In contrast, the combination of alpha-fetoprotein (AFP) and ultrasound (US) yielded an inferior predictive performance (AUC 0.76 (95% CI: 0.69–0.84, p < 0.001), sensitivity 58.5%, and specificity 94.1%). Multivariate analyses revealed that M2P-HCC was an independent predictor of increased risk of HCC (OR = 1.16 [1.09–1.22], p < 0.001). Conclusions: M2P-HCC liquid biopsy demonstrated good performance for early liver cancer screening in high-risk populations of Hepatitis B-related liver cancer, exhibiting better sensitivity than the combination of AFP and US.

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“…Therefore, novel molecular targets for HCC early diagnosis and the development of targeted therapy are critically needed. 2 Glypican-3 (GPC3), a cell-surface glycoprotein, is overexpressed in HCC tissues but not expressed in the kidneys and other liver cell types (hepatic astrocytes, endothelial cells, and fibroblasts). The increased GPC3 expression in HCC indicates the sensitivity and specificity of HCC diagnosis.…”

Section: Introductionmentioning

confidence: 99%

A label-free electrochemical aptasensor based on platinum@palladium nanoparticles decorated with hemin-reduced graphene oxide as a signal amplifier for glypican-3 determination

et al. 2022

Biomater. Sci.

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Biomarker Development Using Liquid Biopsy in Hepatocellular Carcinoma

Cited by 10 publications

References 123 publications

Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis

Hepatocellular carcinoma in patients cured of chronic hepatitis C: Minimal steatosis

Application of the Multi-Omics Liquid Biopsy Method M2P-HCC in Early Liver Cancer Screening for High-Risk Individuals with Hepatitis B-Related Liver Cancer

A label-free electrochemical aptasensor based on platinum@palladium nanoparticles decorated with hemin-reduced graphene oxide as a signal amplifier for glypican-3 determination

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