Research Article: Refinement and validation of a comprehensive clinical diagnostic model (GAMAD) based on gender, age, multitarget circulating tumour DNA methylation signature and commonly used serological biomarkers for early detection of hepatocellular carcinoma: a multicentre, prospective observational study protocol
Abstract:
Introduction Prompt detection of hepatocellular carcinoma (HCC) in patients with chronic liver diseases is critical for enhancing prognosis. Existing imaging techniques and serum markers fall short of clinical needs. This study aims to establish a non-invasive diagnostic model for early HCC detection in the Chinese population. Methods and analysis This prospective, multicentre, observational study will enrol 2000 participants, including HCC patients, those with chronic liver diseases (hepatitis, cirrhosis and benign liver space-occupying lesions), and healthy individuals. The study will collect demographic data and blood samples, which will be used to test ?-fetoprotein (AFP), des-?-carboxy-prothrombin (DCP) and circulating tumour DNA (ctDNA) methylation. The GAMAD ( G ender+ A ge+ M ethylation+ A FP+ D CP) model involving gender, age, ctDNA methylation signature, AFP and DCP will be developed and blindly validated in training and validation sets (1400 and 600 cases, respectively). Primary endpoints include sensitivity, specificity and accuracy (receiver operating characteristic curves; area under the curve value) of GAMAD for HCC and/or high-risk HCC groups. Secondary endpoints involve comparing GAMAD with the established GALAD ( G ender+ A ge+AFP- L 3+ A FP+ D CP) model and each blood index (AFP, DCP and methylation signature) to evaluate: (1) GAMAD’s clinical utility for HCC patients in all stages according to different staging systems; (2) GAMAD’s discrimination ability for patients in various subgroups, including liver cirrhosis (LC) related HCC and LC, hepatitis B virus (HBV) related HCC and HBV, hepatitis C virus (HCV) related HCC and HCV, and non-alcoholic fatty liver disease (NAFLD) related HCC and NAFLD. Ethics and dissemination This trial has been approved by the Medical Ethics Committees of the First Hospital of Jilin University (#22K073-001), the Eastern Hepatobiliary Surgery Hospital, Naval Medical University (#EHBHKY2023-H0003-P001) and Tianjin Third Central Hospital (#IRB2023-007-01). All participants in the trial will provide written informed consent. Results of this study will be disseminated in peer-reviewed scientific journals and at conferences nationally and internationally. Trial registration number NCT05626985 .
Introduction:
Primary hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer death. 1 In China, primary HCC ranks fifth in terms of cancer incidence and the second in terms of cancer-related mortality. China accounts for 45.3% of global HCC cases and 47.1% of HCC deaths. 2 HCC has a poor prognosis worldwide, with a 5-year survival rate ranging 15%–19% in North America, and only 12.5% in China. 3 Due to the lack of distinctive clinical signs in early-stage HCC, most…
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