Accepted for/Published in: JMIR Research Protocols
Date Submitted: Apr 17, 2023
Date Accepted: Aug 18, 2023
Multidimensional analysis of cell-free DNA whole methylome sequencing assay for gastric cancer early detection: protocol for an observational case‒control study
ABSTRACT
Background:
Cancer-related features in cell-free DNA (cfDNA) fragments have gradually been identified and play essential roles in noninvasive early cancer detection. Integrated analysis of several cfDNA features has enhanced detection sensitivity compared to single features.
Objective:
This study aimed to develop and validate an assay based on assessing genomic-scale methylation and fragmentation profiles of plasma cfDNA for early cancer detection and therefore to facilitate early diagnosis of gastric cancer.
Methods:
This is an observational case‒control study. Blood samples will be prospectively collected before gastroscopy from 180 gastric cancer patients and 180 nonmalignant control subjects (healthy or with benign gastric diseases). Cases and controls will be randomly divided into a training and a testing dataset at a ratio of 2:1. Plasma cfDNA will be isolated and extracted, followed by bisulfite-free low-depth whole methylome sequencing. A multidimensional model named THorough Epigenetic Marker Integration Solution (THEMIS) including methylation, fragmentation, and chromosomal copy number alternation will be constructed in the training dataset. The performance of the model in differentiating cancer patients from noncancer controls will then be evaluated in the testing dataset.
Results:
Recruitment began in November 2022 and will be ended in April 2024. As of April 2022, 200 patients have been enrolled. The final data analysis is expected to be completed in September 2024.
Conclusions:
This is the first registered case‒control study designed to investigate a stacked ensemble model integrating several cfDNA features, including methylation pattern, fragmentation profile, and chromosomal copy number change, in identifying the GC population. This study will reveal whether multidimensional analysis of cfDNA will be an effective strategy for differentiating GC patients from nonmalignant individuals in a Chinese population. Clinical Trial: This study was registered at ClinicalTrial.gov (NCT05668910).
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