S2905 HBV-Host Junctional Sequences: A Novel Urine Tumor Marker for Recurrent Hepatitis B-Associated Hepatocellular Carcinoma With Low Alpha-Fetoprotein
Year: 2022
Type: conference-abstract
Abstract: Introduction: Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide. A common risk factor for liver cancer is chronic infection with the hepatitis B virus (CHB). HCC screening and surveillance is limited by diagnostic accuracy of current testing modalities. Prior studies suggest the potential of urine-based biomarkers for HBV-associated HCC (HBV-HCC), as DNA fragments from both virus and tumor have been detected in urine from those with CHB and HCC. As most HBV-HCC tumors contain integrated components of the HBV genome, unique HBV-host junctional sequences (HBV-JS) represent a viable molecular signature to identify HCC. This study evaluated a novel urine-based biomarker platform, utilizing HBV-JS DNA as a possible marker of tumor recurrence in patients with HBV-HCC. Case Description/Methods: Urine sample from HBV-HCC patients with HCC recurrence confirmed by MRI was obtained. HBV-JS were detected by an HBV-targeted NGS assay (JBS Science Inc., Doylestown, PA) followed by ChimericSeq for junction detection. The most abundant NGS-detected junction sequences were then validated by PCR-Sanger sequencing. Quantitative junction-specific PCR assays were developed to track dynamic changes of HBV-JS in the urine specimens. HBV-JS sequences were detected from 2 cases of HBV-HCC with tumor recurrence (Figure). Case 1: A 78-year-old female with HBV-related cirrhosis was diagnosed with HCC in 2015. After microwave ablation, follow-up MRI revealed a new LI-RADS 3 lesion 1 year later. Subsequent imaging remained radiographically indeterminate until 2018 when the lesion was classified as definite HCC (LI-RADS 5). While serial AFP levels were negligible and MRI results variable, the unique HBV-JS DNA, HBV-Chr17, steadily increased from initial diagnosis to HCC recurrence. Case 2: A 74-year-old male with HBV-related cirrhosis was diagnosed with HCC in 2014, which recurred with a LI-RADS 5 lesion after 1 year despite loco-regional therapy. While AFP levels were negligible, two HBV-JS DNA, HBV-Chr11 and HBV-Tert, rapidly increased after initial HCC diagnosis. Discussion: Unique HBV-JS sequences were detectable in the urine of patients with HBV- HCC. These sequences were detectable at increasing levels prior to diagnosis of recurrence of HCC by MRI imaging or AFP elevation. Together, our data suggest that HBV-JS DNA in urine maybe a further biomarker for the detection of HCC recurrence in patients with HBV-HCC.Figure 1.: HBV-host junctional sequences (HBV-JS) were detected from 2 cases of HBV-associated HCC with tumor recurrence
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
OpenAlex ID: W4316085689