Specific epigenetic age acceleration patterns among four molecular subtypes of gastric cancer and their prognostic value.

Epigenomics

Division of Gastroenterology & Hepatology, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Published: May 2021

AI Article Synopsis

  • - The study investigates how the epigenetic clock, specifically methylation age, relates to different molecular subtypes of gastric cancer (GC) and patient survival outcomes.
  • - It finds that certain subtypes, like Epstein-Barr virus-associated GC, show higher methylation age acceleration (AA) than others, which suggests a potential link between AA and clinical characteristics.
  • - Patients with accelerated aging of their tumor tissues have better survival rates, indicating that methylation age could be a valuable prognostic marker and a sign of the molecular subtype for GC.

Article Abstract

To determine the association of the methylation age (Horvath epigenetic clock) of gastric cancer (GC) tissues with molecular subtypes and patient survival. Multivariate regression models were used to determine the association of methylation age acceleration (AA) with the clinical and molecular characteristics of 333 GC patients. Relative to the chromosomal instability subtype, the epigenetic AA was 49.8 (95% CI: 42.7-56.9) years for Epstein-Barr virus, 16.1 (10.6-21.6) years for microsatellite instability, and 6.05 (0.1-11.1) years for genomic stability subtype. GC patients with accelerated aging of tumor tissues had better outcomes (adjusted hazard ratio: 3.13; p = 0.03). Differentially methylated probes in patients with accelerated and decelerated methylation aging enriched in pathways including BMP signaling, HMGB1 signaling, STAT3 signaling and human embryonic stem cell pluripotency. Our results highlight the prognostic value of epigenetic AA in GC and suggest that epigenetic AA is also an indicator of molecular subtype in GC.

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Source
http://dx.doi.org/10.2217/epi-2020-0290DOI Listing

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