A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening

• Published in: International journal of cancer Vol. 154; no. 6; pp. 1111 - 1123
• Main Authors: Fan, Xiao‐Han, Zhang, Yang, Wang, Pei, Song, Qian‐Qian, Wang, Mona, Mejias‐Luque, Raquel, Li, Zhe‐Xuan, Zhou, Tong, Zhang, Jing‐Ying, Liu, Wei‐Dong, Zhang, Lan‐Fu, Li, Wen‐Qing, You, Wei‐Cheng, Gerhard, Markus, Jiao, Yu‐Chen, Wang, Xiao‐Bing, Pan, Kai‐Feng
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.03.2024; Wiley Subscription Services, Inc
• Subjects: biomarker; Biomarkers; Biomarkers, Tumor - genetics; Cancer; Cancer screening; CpG Islands; DNA Methylation; Early Detection of Cancer; Gastric cancer; Genomes; Health risk assessment; Helicobacter Infections - diagnosis; Helicobacter Infections - genetics; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - genetics; Humans; Medical prognosis; Medical research; Medical screening; methylation; Mutation; precancerous lesions; Risk Assessment; Stomach Neoplasms - diagnosis; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; mutation; gastric cancer; biomarker; methylation; precancerous lesions
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.34739

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high‐risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133‐methylation‐marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49‐methylation‐marker panel as well as a 144‐amplicon‐mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori‐specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future. What's new? Genetic and epigenetic markers and environmental factors including Helicobacter pylori promote gastric cancer. Here, the authors established methylation, mutation and H. pylori‐specific antibody biomarker panels based on the analysis of precancerous lesions and gastric cancer cases to construct and validate two integrative models. The risk assessment model aimed to identify suspicious precancerous lesions and gastric cancer cases among asymptomatic screening participants and the detection model to further distinguish gastric cancer from suspected cases. The models showed better performance than a traditional model and high feasibility, paving the way for a noninvasive multianalytical approach for risk assessment and gastric cancer detection.