Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma

• Published in: Langenbeck's archives of surgery Vol. 394; no. 4; pp. 661 - 670
• Main Authors: Lee, Kyung Hwa, Lim, Sang Woo, Kim, Ho Gun, Kim, Dong Yi, Ryu, Seong Yeob, Joo, Jae Kyun, Kim, Jung Chul, Lee, Jae Hyuk
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2009
• Subjects: Abdominal Surgery; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Apoptosis - physiology; Cardiac Surgery; Caspase 8 - metabolism; DNA Methylation; Female; Gene Expression Regulation, Neoplastic - physiology; General Surgery; GPI-Linked Proteins; Humans; Immunohistochemistry; Male; Medicine; Medicine & Public Health; Microdissection; Middle Aged; Neoplasm Invasiveness; Original Article; Promoter Regions, Genetic - physiology; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Member 10c; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Thoracic Surgery; Traumatic Surgery; Tumor Necrosis Factor Decoy Receptors - metabolism; Vascular Surgery; Methylation; Gastric carcinoma; TRAIL
• ISSN: 1435-2443; 1435-2451
• DOI: 10.1007/s00423-009-0484-x

Background and aims To determine the underlying mechanism for the differential expression, the extent of promoter methylation in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-related genes acting downstream of TRAIL was examined in early and advanced gastric carcinomas. Methods The extent of promoter methylation in the DR4 , DR5 , DcR1 , DcR2 , and CASP8 genes was quantified using bisulfite modification and methylation-specific polymerase chain reaction. Results The promoters for DcR1 , DcR2 , and CASP8 were largely unmethylated in early gastric carcinoma, advanced gastric carcinoma, and controls, with no significant difference among them. Protein levels of DR4 , DcR1 , and DcR2 as revealed by immunohistochemistry correlated with the extent of the respective promoter methylation ( P  < 0.05 in all cases). Hypomethylation, rather than hypermethylation, of the DR4 promoter was noted in invasive gastric malignancies, with statistical significance ( P  = 0.003). Conclusion The promoter methylation status of TRAIL receptors in gastric carcinoma may have clinical implications for improving therapeutic strategies in patients with gastric carcinoma.