Aberrant Methylation of Different DNA Repair Genes Demonstrates Distinct Prognostic Value for Esophageal Cancer

• Published in: Digestive diseases and sciences 2011-10, Vol.56 (10), p.2992-3004
• Main Authors: Ling, Zhi-Qiang, Li, Pei, Ge, Ming-Hua, Hu, Fu-Jun, Fang, Xian-Hua, Dong, Zi-Min, Mao, Wei-Min
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Biochemistry; Biological and medical sciences; Cancer; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Case-Control Studies; Chemotherapy; CpG Islands - genetics; DNA; DNA Methylation - genetics; DNA Modification Methylases - genetics; DNA Modification Methylases - metabolism; DNA repair; DNA Repair - genetics; DNA Repair Enzymes - genetics; DNA Repair Enzymes - metabolism; DNA, Neoplasm - genetics; Esophageal cancer; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - genetics; Esophageal Neoplasms - mortality; Esophagus; Esophagus - metabolism; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Genes; Genetic aspects; Genetic research; Hepatology; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Medicine; Medicine & Public Health; Methylation; MutL Protein Homolog 1; MutS Homolog 2 Protein - genetics; MutS Homolog 2 Protein - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncology; Original Article; Predictive Value of Tests; Prognosis; Squamous cell carcinoma; Transferases; Transplant Surgery; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-011-1774-z

Background DNA mismatch repair (MMR) deficiency results in a strong mutator phenotype and high-frequency microsatellite instability (MSI-H), which are the hallmarks of many tumors. Aim The objective of this study is to investigate the promoter CpG island methylation status of mismatch repair genes human mutL homolog 1 ( hMLH1 ), human mutS homolog 2 ( hMSH2 ), and O 6 -methylguanine-DNA methyltransferase ( MGMT ) in esophageal squamous cell carcinoma (ESCC) and its roles in alkylating agents chemotherapy. Methods Real-time methylation-specific polymerase chain reaction (PCR) (real-time MSP) was employed to detect promoter CpG island methylation of the hMLH1 , hMSH2 , as well as MGMT genes in 235 surgical tumor tissue samples from ESCC patients and their corresponding normal tissue samples. Results Promoter CpG island methylation of hMLH1 , hMSH2 , and MGMT were detectable in 43.4, 28.9, and 40.4% of ESCC tumor DNA, respectively, and the loss rates of hMLH1, hMSH2, and MGMT protein expression were 48.6, 34.5, and 40.9% in tumor tissues, respectively. For the entire population of 235 ESCC patients who were enrolled in operating treatment combined with radiotherapy and chemotherapy with alkylating agents, there was a significant difference in the overall survival between patients with methylated MGMT promoter and those with an unmethylated MGMT promoter ( P