Methylation Assessment of Two DKK2 and DKK4 Genes in Oral Squamous Cell Carcinoma Patients

  • Sedigheh KHEIRANDISH Department of Oral and Maxillofacial Pathology, School of Dentistry, Bushehr University of Medical Sciences, Bushehr, Iran
  • Nosratollah ESHGHYAR Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
  • Farzad YAZDANI Department of Otorhinolaryngology, Amir A’lam Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Pouyan AMINI SHAKIB Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
  • Ali HOSSEINI-BERESHNEH Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  • Zahra NOURI Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Ali KHEIRANDISH Department of Medical Genetics, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
  • Fatemeh KARAMI Mail Department of Medical Genetics, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
Methylation, Oral squamous cell carcinoma, Methylation-specific polymerase chain reaction


Background: Oral squamous cell carcinoma (OSCC) is one of the most important types of oral malignancies. DKK gene family members as well as DKK2/4 have critical roles in regulation of Wnt signaling as one of the main determining pathway in oral carcinogenesis. This study aimed to identify promoter methylation status of DKK2/4 genes to provide possible biomarkers for early detection and treatment of OSCC patients.

Methods: A case control study was performed on 31 fresh tissues obtained from oral cavity of patients affected by OSCC and 31 fresh corresponding tissues from normal healthy controls in Tehran and, between the years of 2016-2018. Purified DNA from tissue samples was subjected to bisulfite treatment and then methylation specific polymerase chain reaction (MSP-PCR) was carried out on treated DNA samples.

Results: DKK4 promoter was methylated in none of OSCC samples while it was methylated in 16.1% of healthy controls. 16.1% of OSCC samples were detected to be semimethylated and 22.6% of healthy normal samples were methylated for DKK2 promoter gene. Meaningful difference was found in DKK4 promoter methylation among OSCC patients and healthy controls. Significant correlation was found between DKK4 promoter methylation and tumor grade. The age of all enrolled samples was demonstrated to have strong effect on promoter methylation of studied genes.

Conclusion: Hypomethylation of DKK2 and DKK4 genes in higher grades of OSCC samples may indicate the pivotal role of their expression in tumor cells invasion and progression through modulation of Wnt signaling pathway. Further study required to determine simultaneous expression of those genes and Wnt signaling elements at mRNA and protein levels.


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How to Cite
KHEIRANDISH S, ESHGHYAR N, YAZDANI F, AMINI SHAKIB P, HOSSEINI-BERESHNEH A, NOURI Z, KHEIRANDISH A, KARAMI F. Methylation Assessment of Two DKK2 and DKK4 Genes in Oral Squamous Cell Carcinoma Patients. Iran J Public Health. 49(10):1947-1953.
Original Article(s)