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

Xiao Han Fan, Yang Zhang, Pei Wang, Qian Qian Song, Mona Wang, Raquel Mejias-Luque, Zhe Xuan Li, Tong Zhou, Jing Ying Zhang, Wei Dong Liu, Lan Fu Zhang, Wen Qing Li, Wei Cheng You, Markus Gerhard, Yu Chen Jiao, Xiao Bing Wang, Kai Feng Pan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1111-1123
Number of pages13
JournalInternational Journal of Cancer
Volume154
Issue number6
DOIs
StatePublished - 15 Mar 2024

Keywords

  • biomarker
  • gastric cancer
  • methylation
  • mutation
  • precancerous lesions

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