Lower LINE-1 Methylation is Associated with Promoter Hypermethylation and Distinct Molecular Features in Gastric Cancer

Abstract

Aim: To investigate the associations between LINE1 methylation, an indicator for genome-wide hypomethylation, molecular and clinicopathological characteristics of gastric cancer (GC) patients. Patients & methods:LINE1 methylation statuses were examined in paired cancerous, non-neoplastic mucosa from 217 GC and gastric mucosa from separate group of 224 noncancer patients. CpG island methylator phenotype, TP53 and KRAS mutation, MLH1 methylation status and promoter hypermethylation of GC related and H. pylori-related genes were examined. Results: Lower LINE1 methylation was observed in primary GC compared with non-neoplastic gastric mucosa and associated with CpG island methylator phenotype, TP53 mutation, MLH1 methylation and promoter hypermethylation of GC related and H. pylori-related genes. Conclusion: Lower LINE1 methylation correlates specific molecular subtypes and promoter hypermethylation in GC.

Keywords::

• Helicobacter pylori
• LINE1
• TP53 mutation
• CpG island methylator phenotype
• gastric cancer
• genome-wide hypomethylation
• molecular subtypes
• promoter hypermethylation

Author contributors

Study concept and design (S Tahara, T Tahara, T Shibata); acquisition of data (S Tahara, T Tahara, T Shibata, N Horiguchi, M Okubo, T Tahara, D Yoshida); analysis and interpretation of data (S Tahara, T Tahara, T Shibata, K Funasaka, Y Nakagawa, T Tsukamoto, N Ohmiya) and writing manuscript (S Tahara, T Tahara).

Financial & competing interests disclosure

This work was supported by JSPS KAKENHI Grant-in-Aid for Young Scientists (B) Grant Number JP26870685. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

For the discovery cohort informed written consent was obtained from all patients. The study was approved by the Medical Ethical Committees of the Fujita Health University.

Additional information

Funding

This work was supported by JSPS KAKENHI Grant-in-Aid for Young Scientists (B) Grant Number JP26870685. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.