Plasma cell‐free DNA methylome‐based liquid biopsy for accurate gastric cancer detection

Abstract

AbstractEarly detection plays a critical role in mitigating mortality rates linked to gastric cancer. However, current clinical screening methods exhibit suboptimal efficacy. Methylation alterations identified from cell‐free DNA (cfDNA) present a promising biomarker for early cancer detection. Our study focused on identifying gastric cancer‐specific markers from cfDNA methylation to facilitate early detection. We enrolled 150 gastric cancer patients and 100 healthy controls in this study, and undertook genome‐wide methylation profiling of cfDNA using cell‐free methylated DNA immunoprecipitation and high‐throughput sequencing. We identified 21 differentially methylated regions (DMRs) between the gastric tumor and nontumor groups using multiple algorithms. Subsequently, using the 21 DMRs, we developed a gastric cancer detection model by random forest algorithm in the discovery set, and validated the model in an independent set. The model was able to accurately discriminate gastric cancer with a sensitivity and specificity of 93.90% and 95.15% in the discovery set, respectively, and 88.38% and 94.23% in the validation set, respectively. These results underscore the efficacy and accuracy of cfDNA‐derived methylation markers in distinguishing early stage gastric cancer. This study highlighted the significance of cfDNA methylation alterations in early gastric cancer detection.