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Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma. | LitMetric

AI Article Synopsis

  • Gastric adenocarcinoma ranks as the third leading cause of cancer-related deaths globally, highlighting the need for better detection methods.
  • This study identifies and validates novel methylated DNA markers (MDMs) from tissue samples of patients across the U.S. and South Korea, demonstrating their effectiveness in distinguishing gastric adenocarcinoma at high rates of accuracy.
  • The findings suggest that these MDMs not only show potential for noninvasive screening through blood plasma tests but also underscore the varying points of methylation during cancer development, which is important for clinical applications.

Article Abstract

Gastric adenocarcinoma is the third most common cause of cancer mortality worldwide. Accurate and affordable noninvasive detection methods have potential value for screening and surveillance. Herein, we identify novel methylated DNA markers (MDM) for gastric adenocarcinoma, validate their discrimination for gastric adenocarcinoma in tissues from geographically separate cohorts, explore marker acquisition through the oncogenic cascade, and describe distributions of candidate MDMs in plasma from gastric adenocarcinoma cases and normal controls. Following discovery by unbiased whole-methylome sequencing, candidate MDMs were validated by blinded methylation-specific PCR in archival case-control tissues from U.S. and South Korean patients. Top MDMs were then assayed by an analytically sensitive method (quantitative real-time allele-specific target and signal amplification) in a blinded pilot study on archival plasma from gastric adenocarcinoma cases and normal controls. Whole-methylome discovery yielded novel and highly discriminant candidate MDMs. In tissue, a panel of candidate MDMs detected gastric adenocarcinoma in 92% to 100% of U.S. and South Korean cohorts at 100% specificity. Levels of most MDMs increased progressively from normal mucosa through metaplasia, adenoma, and gastric adenocarcinoma with variation in points of greatest marker acquisition. In plasma, a 3-marker panel ( detected 86% (95% CI, 71-95) of gastric adenocarcinomas at 95% specificity. Novel MDMs appear to accurately discriminate gastric adenocarcinoma from normal controls in both tissue and plasma. The point of aberrant methylation during oncogenesis varies by MDM, which may have relevance to marker selection in clinical applications. Further exploration of these MDMs for gastric adenocarcinoma screening and surveillance is warranted. .

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6239895PMC
http://dx.doi.org/10.1158/1078-0432.CCR-17-3364DOI Listing

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