A multi‐analyte cell‐free DNA–based blood test for early detection of hepatocellular carcinoma

Abstract

The limited performance of guideline-recommended abdominal ultrasound and serum alpha-fetoprotein (AFP) highlights the urgent, unmet need for new biomarkers for more accurate detection of early hepatocellular carcinoma (HCC). To this end, we have conducted a prospective clinical validation study to evaluate the performance of the HelioLiver Test, a multi-analyte blood test combining cell-free DNA methylation patterns, clinical variables, and protein tumor markers. A blinded, multicenter validation study was performed with 247 subjects, including 122 subjects with HCC and 125 control subjects with chronic liver disease. The performance of the HelioLiver Test was compared with AFP and the GALAD score as established HCC surveillance blood tests. The performance of the HelioLiver Test (area under the receiver operating characteristic curve [AUROC] = 0.944) was superior to both AFP (AUROC

Emerging liquid biopsy techniques for early detection of hepatocellular carcinoma, prognostication, and disease monitoring

“…Early‐stage HCC sensitivity of the cfDNA panel was significantly higher than AFP and the GALAD panel (82% vs. 40% and 71%, respectively), although AFP and GALAD both had higher specificities 6 . A subsequent multi‐center case–control study similarly evaluated a methylated DNA panel and found superior sensitivity for early‐stage HCC compared to AFP and GALAD (76% vs. 57% and 65%, respectively) albeit with lower specificities (91% vs. 97% and 94%, respectively) 7 . Based on these promising data, both panels are currently undergoing prospective validation.…”

“…6 A subsequent multi-center case-control study similarly evaluated a methylated DNA panel and found superior sensitivity for early-stage HCC compared to AFP and GALAD (76% vs. 57% and 65%, respectively) albeit with lower specificities (91% vs. 97% and 94%, respectively). 7 Based on these promising data, both panels are currently undergoing prospective validation.…”

Multimodal Epigenetic Sequencing Analysis (MESA) of Cell-free DNA for Non-invasive Cancer Detection

“…The Helio ECLIPSE™ platform was used to analyze cfDNA extracted from patient specimens as previously described 40 . Brie y, total cfDNA was isolated from specimens by using either (Cohort 1) a QIAsymphony DSP Circulating DNA Kit (QIAGEN, USA) or (Cohort 2) the EliteHealth cfDNA Extraction Kit (EliteHealth, China).…”

Recent advances in liquid biopsy in cancers: Diagnosis, disease state and treatment response monitoring

“…Moss et al 51 described a sensitivity of 80% and specificity of 97% (n = 235) when using cfDNA to diagnose treatment-naïve breast cancer on the basis of a breast-specific DNA methylation signature. In a clinical validation study on hepatocellular carcinoma (HCC), Lin et al 52 evaluated a comprehensive analysis method integrating cell-free DNA methylation patterns, clinical variables and protein tumour markers. This multianalyte test (AUC of 0.944) showed better diagnostic performance than both alpha foetal protein (AFP, a biomarker of HCC; AUC of 0.851) and the GALAD score (an evaluation system including sex, age and AFP to detect HCC; AUC of 0.899).…”

“…described a sensitivity of 80% and specificity of 97% ( n = 235) when using cfDNA to diagnose treatment‐naïve breast cancer on the basis of a breast‐specific DNA methylation signature. In a clinical validation study on hepatocellular carcinoma (HCC), Lin et al 52 . evaluated a comprehensive analysis method integrating cell‐free DNA methylation patterns, clinical variables and protein tumour markers.…”