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

Author:

Fan Xiao‐Han1,Zhang Yang123,Wang Pei4,Song Qian‐Qian4,Wang Mona2356,Mejias‐Luque Raquel2356,Li Zhe‐Xuan123,Zhou Tong1,Zhang Jing‐Ying1,Liu Wei‐Dong7,Zhang Lan‐Fu8,Li Wen‐Qing123,You Wei‐Cheng123,Gerhard Markus2356,Jiao Yu‐Chen4,Wang Xiao‐Bing4ORCID,Pan Kai‐Feng123ORCID

Affiliation:

1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology Peking University Cancer Hospital & Institute Beijing China

2. PYLOTUM Key Joint Laboratory for Upper GI Cancer, Technische Universität München/Peking University Cancer Hospital & Institute Munich Germany

3. PYLOTUM Key Joint Laboratory for Upper GI Cancer, Technische Universität München/Peking University Cancer Hospital & Institute Beijing China

4. State Key Lab of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

5. Technical University of Munich (TUM), School of Medicine, Institute for Medical Microbiology, Immunology and Hygiene Munich Germany

6. German Center for Infection Research Munich Germany

7. Linqu County Public Health Bureau Linqu China

8. Linqu County People's Hospital Linqu China

Abstract

AbstractEffective 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.

Funder

Natural Science Foundation of Beijing Municipality

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

Subject

Cancer Research,Oncology

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