Abstract
BackgroundThere is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis. However, there is a lack of information on how this epigenetic process differs in tumors originating at different sites in the stomach.The aim of this study is to assess the methylation profiles of the MLH1, MGMT, and DAPK-1 genes in cancerous tissues from different stomach sites.MethodsSamples were acquired from 81 patients suffering stomach adenocarcinoma who underwent surgery for gastric cancer in the Lithuanian University of Health Sciences Hospital Kaunas Clinics in 2009–2012. Gene methylation was investigated with methylation-specific PCR. The study was approved by the Lithuanian Biomedical Research Ethics Committee.ResultsThe frequencies of methylation in cancerous tissues from the upper, middle, and lower thirds of the stomach were 11.1, 23.1, and 45.4 %, respectively, for MLH1; 22.2, 30.8, and 57.6 %, respectively, for MGMT; and 44.4, 48.7, and 51.5 %, respectively, for DAPK-1. MLH1 and MGMT methylation was observed more often in the lower third of the stomach than in the upper third (p < 0.05). In the middle third, DAPK-1 promoter methylation was related to more-advanced disease in the lymph nodes (N2–3 compared with N0–1 [p = 0.02]) and advanced tumor stage (stage III rather than stages I–II [p = 0.05]). MLH1 and MGMT methylation correlated inversely when the tumor was located in the lower third of the stomach (coefficient, –0.48; p = 0.01). DAPK-1 and MLH1 methylation correlated inversely in tumors in the middle-third of the stomach (coefficient, –0.41; p = 0.01).ConclusionGene promoter methylation depends on the gastric tumor location.
Highlights
There is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis
A sex-based subgroup analysis revealed that mutL homolog 1 (MLH1) methylation in the cancer tissues of the lower-third stomach was typical of the female population (p = 0.01), whereas MGMT methylation was only statistically significant in the male group (p = 0.03)
The results of our study indicate an inverse correlation between the methylation of the MLH1 and MGMT genes in gastric cancer tissues when the tumor was located in the lower third of the stomach
Summary
There is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis. The aim of this study is to assess the methylation profiles of the MLH1, MGMT, and DAPK-1 genes in cancerous tissues from different stomach sites. More than 90 % of stomach cancers are diagnosed as adenocarcinoma [1]. Recent scientific data show that the prognosis of gastric adenocarcinoma depends on its histological type, and on the tumor location in the stomach. The relative risk of gastric cancer occurring in patients with corpus-predominant gastritis is higher than in those with predominantly antral gastritis [6]. Does this fact indicate different carcinogenic processes in the stomach antrum and corpus? Does this fact indicate different carcinogenic processes in the stomach antrum and corpus? There are no data to either exclude or confirm this
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
