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A Novel Blood-Based Panel of Methylated DNA and Protein Markers for Detection of Early-Stage Hepatocellular Carcinoma.
Chalasani, Naga P; Ramasubramanian, Tiruvidaimarudur S; Bhattacharya, Abhik; Olson, Marilyn C; Edwards V, David K; Roberts, Lewis R; Kisiel, John B; Reddy, K Rajender; Lidgard, Graham P; Johnson, Scott C; Bruinsma, Janelle J.
Afiliação
  • Chalasani NP; Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: nchalasa@iu.edu.
  • Ramasubramanian TS; Exact Sciences Development Corporation, Madison, Wisconsin.
  • Bhattacharya A; Exact Sciences Development Corporation, Madison, Wisconsin.
  • Olson MC; Exact Sciences Development Corporation, Madison, Wisconsin.
  • Edwards V DK; Exact Sciences Corporation, Madison, Wisconsin.
  • Roberts LR; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
  • Kisiel JB; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
  • Reddy KR; Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  • Lidgard GP; Exact Sciences Corporation, Madison, Wisconsin.
  • Johnson SC; Exact Sciences Corporation, Madison, Wisconsin.
  • Bruinsma JJ; Exact Sciences Development Corporation, Madison, Wisconsin.
Clin Gastroenterol Hepatol ; 19(12): 2597-2605.e4, 2021 12.
Article em En | MEDLINE | ID: mdl-32889146
ABSTRACT
BACKGROUND &

AIMS:

Hepatocellular carcinoma (HCC) can be treated effectively if detected at an early stage. Recommended surveillance strategies for at-risk patients include ultrasound with or without α-fetoprotein (AFP), but their sensitivity is suboptimal. We sought to develop a novel, blood-based biomarker panel with improved sensitivity for early-stage HCC detection.

METHODS:

In a multicenter, case-control study, we collected blood specimens from patients with HCC and age-matched controls with underlying liver disease but without HCC. Ten previously reported methylated DNA markers (MDMs) associated with HCC, methylated B3GALT6 (reference DNA marker), and 3 candidate proteins, including AFP, were assayed and analyzed by a logistic regression algorithm to predict HCC cases. The accuracy of the multi-target HCC panel was compared with that of other blood-based biomarkers for HCC detection.

RESULTS:

The study included 135 HCC cases and 302 controls. We identified a multi-target HCC panel of 3 MDMs (HOXA1, EMX1, and TSPYL5), B3GALT6 and 2 protein markers (AFP and AFP-L3) with a higher sensitivity (71%, 95% CI 60-81%) at 90% specificity for early-stage HCC than the GALAD score (41%, 95% CI 30-53%) or AFP ≥7.32 ng/mL (45%, 95% CI 33-57%). The AUC for the multi-target HCC panel for detecting any stage HCC was 0.92 compared with 0.87 for the GALAD score and 0.81 for AFP alone. The panel performed equally well in important subgroups based on liver disease etiology, presence of cirrhosis, or sex.

CONCLUSIONS:

We developed a novel, blood-based biomarker panel that demonstrates high sensitivity for early-stage HCC. These data support the potential for liquid biopsy detection of early-stage HCC to clinically benefit at-risk patients. This study was registered on ClinicalTrials.gov (NCT03628651).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Clinical_trials / Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Clin Gastroenterol Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Clinical_trials / Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Clin Gastroenterol Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2021 Tipo de documento: Article