HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Epigenetic clustering of gastric carcinomas based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome.

Abstract
The aim of this study was to clarify the significance of DNA methylation alterations during gastric carcinogenesis. Single-CpG resolution genome-wide DNA methylation analysis using the Infinium assay was performed on 109 samples of non-cancerous gastric mucosa (N) and 105 samples of tumorous tissue (T). DNA methylation alterations in T samples relative to N samples were evident for 3861 probes. Since N can be at the precancerous stage according to the field cancerization concept, unsupervised hierarchical clustering based on DNA methylation levels was performed on N samples (βN) using the 3861 probes. This divided the 109 patients into three clusters: A (n = 20), B1 (n = 20), and B2 (n = 69). Gastric carcinomas belonging to Cluster B1 showed tumor aggressiveness more frequently than those belonging to Clusters A and B2. The recurrence-free and overall survival rates of patients in Cluster B1 were lower than those of patients in Clusters A and B2. Sixty hallmark genes for which βN characterized the epigenetic clustering were identified. We then focused on DNA methylation levels in T samples (βT) of the 60 hallmark genes. In 48 of them, including the ADAM23, OLFM4, AMER2, GPSM1, CCL28, DTX1 and COL23A1 genes, βT was again significantly correlated with tumor aggressiveness, and the recurrence-free and/or overall survival rates. Multivariate analyses revealed that βT was a significant prognostic factor, being independent of clinicopathological parameters. These data indicate that DNA methylation profiles at the precancerous stage may be inherited by gastric carcinomas themselves, thus determining tumor aggressiveness and patient outcome.
AuthorsKazuhiro Yamanoi, Eri Arai, Ying Tian, Yoriko Takahashi, Sayaka Miyata, Hiroki Sasaki, Fumiko Chiwaki, Hitoshi Ichikawa, Hiromi Sakamoto, Ryoji Kushima, Hitoshi Katai, Teruhiko Yoshida, Michiie Sakamoto, Yae Kanai
JournalCarcinogenesis (Carcinogenesis) Vol. 36 Issue 5 Pg. 509-20 (May 2015) ISSN: 1460-2180 [Electronic] England
PMID25740824 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Copyright© The Author 2015. Published by Oxford University Press.
Chemical References
  • Biomarkers, Tumor
  • RNA, Messenger
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (genetics)
  • Case-Control Studies
  • DNA Methylation
  • Epigenesis, Genetic (genetics)
  • Female
  • Follow-Up Studies
  • Gastric Mucosa (metabolism, pathology)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local (genetics, mortality, pathology)
  • Neoplasm Staging
  • Precancerous Conditions (genetics, mortality, pathology)
  • Prognosis
  • RNA, Messenger (genetics)
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms (genetics, mortality, pathology)
  • Survival Rate

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: