Promoter hypermethylation of RAR-β tumor suppressor gene in gastric carcinoma: Association with histological type and clinical outcomes

Article type: Research Article

Authors: Mohsenzadeh, Maedeh^a | Sadeghi, Rouhallah Najjar^{b; c; *} | Vahedi, Mohsen^d | Kamani, Fereshteh^e | Hashemi, Mehrdad^f | Asadzadeh, Hamid^g | Zali, Mohammad Reza^g

Affiliations: [a] Department of Cellular and Molecular Sciences, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran | [b] Basic and Molecular Epidemiology of Gastrointestinal Disorders, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [c] Faculty of Medicine, Department of Clinical Biochemistry, Mazandaran University of Medical Sciences, Sari, Iran | [d] Department of Biostatistics, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran | [e] Department of Surgery, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran | [f] Department of Genetics, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran | [g] Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Correspondence: [*] Corresponding author: Rouhallah Najjar Sadeghi, Basic and Molecular Epidemiology of Gastrointestinal Disorders, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Yaman St. Shahid Chamran Highway, Tehran 1985711151, Iran. E-mail: najjarsadeghi@yahoo.com;FacultyofMedicine,DepartmentofClinicalBiochemistry,MazandaranUniversityofMedicalSciences,Sari,Iran.E-mail:r.nsadeghi@mazums.ac.ir.

Abstract: BACKGROUND: While gastric cancer is a common cancer in the world and Iran, its molecular mechanisms are not fully understood as yet. Epigenetic modifications can lead to alteration of gene expression and development of tumorigenesis mechanisms. METHODS: To clarify the difference in DNA methylation pattern of histological types in gastric carcinoma, CpG islands in the promoters of retinoic acid receptor β gene (RAR-β) was studied using methylation-specific PCR. RESULTS: In gastric cancer tissues, hypermethylation frequency of RAR-β gene was respectively 61 and 33% for diffuse and intestinal type. In diffuse type, hypermethylation of RAR-β has been significantly associated with invasion (P= 0.007), differentiation (P= 0.033) and location (P= 0.012) of the tumor. However, hypermethylation of RAR-β correlated only with tumor size (P= 0.029) in intestinal type. For adjacent non-tumor samples, hypermethylation of RAR-β was not detected and there was no significant association between age of diagnosis and hypermethylation of RAR-β in both types of gastric cancer. CONCLUSIONS: These results support previous findings denoting a distinct profile of promoter hypermethylation status in the development of the intestinal and diffuse type of gastric carcinoma and the process of the tumorigenesis in these subtypes of gastric cancer is different from each other.

Keywords: DNA hypermethylation, epigenetic, RAR-β, gastric cancer, diffuse-type, intestinal-type, methylation specific PCR, invasion, tumor

DOI: 10.3233/CBM-160331

Journal: Cancer Biomarkers, vol. 20, no. 1, pp. 7-15, 2017