Liver cancer methylation markers and uses thereof
Inventors
Zhang, Kang • Hou, Rui • Zheng, Lianghong
Assignees
Helio Health Inc • University of California San Diego UCSD
Publication Number
US-12359257-B2
Publication Date
2025-07-15
Expiration Date
2037-07-06
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Abstract
Disclosed herein are methods and kits for identifying a subject as having liver cancer. Also provided herein are methods and kits for determining the prognosis of a subject having liver cancer and for determining the progression of liver cancer in a subject.
Core Innovation
The invention provides methods and kits for identifying a subject as having liver cancer, determining the prognosis of a subject with liver cancer, and monitoring the progression of liver cancer in a subject. These methods involve generating a methylation profile comprising specific biomarkers from extracted genomic DNA obtained from a biological sample of the subject. The extracted DNA is processed with a deaminating agent to produce deaminated nucleotides suitable for detecting methylation status.
The problem addressed is the need for improved diagnostic and prognostic methods for liver cancer, as current procedures often begin after symptoms manifest, leading to costly, invasive, and sometimes inaccurate diagnoses due to inaccessible areas and late detection. Late diagnosis correlates with high morbidity and mortality, highlighting the requirement for sensitive, specific, and minimally invasive diagnostic and prognostic tools.
Claims Coverage
The claims include one independent method claim focusing on treating liver cancer by analyzing the methylation status of biomarker cg10673833 in cell-free DNA, with further claims elaborating on sample origin, detection techniques, cancer types, and additional biomarkers. The inventive features delineate the core steps and components of this treatment method.
Detection of liver cancer via methylation profiling of cg10673833 in cfDNA
A method comprises obtaining treated genomic DNA derived from a cell-free DNA sample from a subject and performing next-generation sequencing to determine the methylation status of biomarker cg10673833, followed by generating a methylation profile, comparing it with a control to identify liver cancer, and administering an effective therapeutic agent accordingly.
Use of cell-free DNA from blood for non-invasive liver cancer diagnosis
The cfDNA sample used for methylation analysis is derived from a blood sample, enabling a non-invasive or minimally invasive method for liver cancer detection.
Quantification of methylation rate as a diagnostic metric
The methylation status of cg10673833 is quantified as a methylation rate, defined as the proportion of sequence reads showing methylation at cg10673833 divided by the total reads covering this site.
Applicability to various liver cancer types
The liver cancer identified includes relapsed or refractory liver cancer, metastatic liver cancer, and specific subtypes such as hepatocellular carcinoma, fibrolamellar HCC, cholangiocarcinoma, angiosarcoma, or hepatoblastoma.
Treatment method including extraction and processing of genomic DNA
The method further comprises extracting genomic DNA from the cfDNA sample and treating it with a deaminating agent to prepare it for the methylation analysis.
Use of digital PCR sequencing in methylation analysis
Next-generation sequencing technique includes digital PCR sequencing methods to detect the methylation status with high sensitivity and specificity.
Expanded methylation profile including additional biomarkers
The methylation profile may further comprise methylation data of additional biomarkers cg07360250, cg08550839, cg13499300, ch.7.135065R, and cg14054357 to enhance diagnostic accuracy.
The claims collectively cover a method of diagnosing and treating liver cancer by analyzing methylation status of specific biomarkers, primarily cg10673833 in cell-free DNA derived from blood, through next-generation sequencing and comparison with controls, allowing identification of liver cancer types including metastatic and refractory forms, and guiding therapeutic treatment with agents such as sorafenib tosylate, doxorubicin, fluorouracil, and cisplatin.
Stated Advantages
Enhanced sensitivity and specificity for liver cancer diagnosis through DNA methylation profiling.
Non-invasive or minimally invasive diagnostic methods via analysis of cell-free DNA from blood samples.
Provision of prognostic information to guide treatment decisions based on methylation scores correlating with survival outcomes.
Ability to monitor progression or remission of liver cancer through changes in methylation profiles over time.
Documented Applications
Diagnosis of liver cancer by generating and analyzing methylation profiles of specific biomarkers from biological samples.
Determining prognosis and survival predictions for subjects with liver cancer using methylation scores calculated from biomarker methylation profiles.
Monitoring disease progression or response to therapy in liver cancer patients by serial assessments of methylation status in cell-free DNA.
Selection and administration of effective therapeutic agents such as sorafenib tosylate, doxorubicin, fluorouracil, and cisplatin based on methylation profiling outcomes.
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