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Promoter Dna Methylation and Mrna Expression Level of P16 Gene in Oral Squamous Cell Carcinoma: Correlation With Clinicopathological Characteristics Publisher Pubmed



Allameh A1 ; Moazeniroodi A1, 2 ; Harirchi I3 ; Ravanshad M4 ; Motieelangroudi M3 ; Garajei A3, 5 ; Hamidavi A1 ; Mesbahnamin SA1
Authors
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Authors Affiliations
  1. 1. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  2. 2. Department of Clinical Biochemistry, Iranshahr University of Medical Sciences, Iranshahr, Iran
  3. 3. Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Medical Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  5. 5. Department of Oral and Maxillofacial Surgery, School of Dentistry and Department of Head and Neck Surgical Oncology and Reconstructive Surgery, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Pathology and Oncology Research Published:2019


Abstract

The aim of this study was to investigate the relationship between p16 methylation and its expression in oral squamous cell carcinoma (OSCC). Also the contribution of clinicopathological factors, HPV infection and smoking in p16 expression and promoter methylation has been investigated. In this study 67 consecutive OSCC patients and 59 normal individuals were enrolled. All patients were candidates for surgery of oral cavity and fresh tumor biopsies were collected and processed for DNA and RNA extraction. Normal gingival tissues were collected from individuals referred to dentistry clinic and considered as controls. All the cases and controls were checked for HPV infection and then promoter methylation and expression of p16 gene were determined using Methylation-specific PCR (MSP) and real-time PCR (QPCR), respectively. Methylation of p16 in tumors and normal tissues were 59.7 and 38.9%, respectively. Most of hypermethylated samples (>82%) were in high grades. P16 methylation was comparable in HPV+ and HPV- patients or smokers. P16 was overexpressed (~3 fold; p = 0.044) in HPV+ tumors, but it was significantly down-regulated in smoker patients (40% of all tumors). Comparison of P16 expression in OSCC tumors with different degrees of promoter methylation further suggest the relationship of methylation rate and down-regulation of P16 expression. The p16 methylation and expression was differentially affected in patients with HPV infection and the smoker cases. Regardless of the influence of environmental factors, it appears that P16 status is useful for classifying patients with OSCC and for influencing treatment strategies in accordance with this classification. Moreover, targeting the upregulation of p16 could be a promising therapeutic option. © 2018, Aranyi Lajos Foundation.
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