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Virus exposure profile for detecting early hepatocellular carcinoma

A hepatocellular carcinoma, virus technology, applied in the field of identifying subjects with early-stage hepatocellular carcinoma, can solve problems such as non-existence

Pending Publication Date: 2022-07-15
US DEPT OF HEALTH & HUMAN SERVICES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

VES is based on the presence or absence of antibodies against a particular virus strain in the subject

Method used

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  • Virus exposure profile for detecting early hepatocellular carcinoma
  • Virus exposure profile for detecting early hepatocellular carcinoma
  • Virus exposure profile for detecting early hepatocellular carcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] Example 1: Method

[0078] This example describes the materials and experimental procedures used for the studies described in Example 2.

[0079] Participants and VirScan Analysis

[0080] The patient cohort consisted of 899 sequentially enrolled participants (clinicaltrials.gov number: NCT0091375), including 150 HCC cases, 337 CLD as at-risk individuals (HR or AR, used interchangeably), and 412 healthy volunteers as an age- and sex-matched population control (PC) ( Figure 1A ).

[0081] study cohort

[0082] UMD queue. To measure virus-host interactions, 899 participants were recruited. Participants were grouped into (1) a population control group (PC, n=412) if they were relatively healthy without any liver disease diagnosis; (2) if diagnosed with chronic liver disease (hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), aflatoxins from fungal contamination, alcohol, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatit...

Embodiment 2

[0107] Example 2: Viral Exposure Signature (VES) for Diagnosis of Hepatocellular Carcinoma (HCC)

[0108] This example describes the development of two viral exposure signatures - the first VES based on detection of 61 virus strains and the second VES based on detection of 31 virus strains - to identify subjects at risk for HCC.

[0109] OVERVIEW OF VIRUS EXPOSURE CHARACTERISTICS

[0110] VirScan applied a phage display library covering 93,904 viral epitopes, representing 206 human virus species and over 1000 virus strains, to screen for prior exposure history (Xu et al., Science 2015;348:aaa0698). Phage particles with epitopes recognized by participant antibodies were immunoprecipitated (Phage-IP), followed by sequencing of the encoded DNA barcodes ( Figure 1A ). A case-control design of the Maryland (NCI-UMD) cohort was used to characterize virus exposure. Enrollment and enrolment of study subjects at Figure 5E As outlined in CONSORT guidelines (Schulz et al., BMJ340:c...

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Abstract

Virus exposure signatures (VESs) are described that can identify early, pre-symptomatic hepatocellular carcinoma (HCC) in a risk patient. VESs are developed using serological analysis and synthetic virome techniques to identify unique viral peptide epitopes corresponding to 61 viruses. Methods of identifying subjects with early (pre-symptom) HCC using VESs are described.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of US Provisional Application No. 62 / 914,138, filed October 11, 2019, which is incorporated herein by reference in its entirety. technical field [0003] The present disclosure relates to viral exposure signatures and their use for identifying subjects with early stage (presymptomatic) hepatocellular carcinoma. [0004] Statement of Government Support [0005] This invention was made with government support under Project No. Z01-BC010313 awarded by the National Institutes of Health. The government has certain rights in the invention. Background technique [0006] Hepatocellular carcinoma (HCC) is considered a virus-related malignancy of which hepatitis B and C viruses (HCV and HBV) are the major etiologies (Farazi et al., Nat Rev Cancer 2006; 6:674-687). Viral hepatitis causes inflammation and chronic liver disease (CLD), which can lead to fibrosis, cirrhosis, and ultimately HCC...

Claims

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Application Information

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IPC IPC(8): C12Q1/6804C12N15/10C12Q1/6883
CPCC12Q1/6883C12Q1/6804C12N15/1037C40B40/02Y02A50/30A61P1/16G01N33/56983G01N33/57438
Inventor 王心伟J·刘W·唐
Owner US DEPT OF HEALTH & HUMAN SERVICES
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