Volume 20, Issue 3 (5-2026)
MGj 2026, 20(3): 197-204 |
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Yazdanian A, Aghaei A M, Hosseinzadeh Moghbeli A H, Akbari M, Maghsoudinia E, Zarrehdar H, et al . The Effect of CDKN2A Gene Methylation Alterations on the Expression of CDK-4 and CDK-6 in Tumor and Tumor-Margin Tissues of Patients with Thyroid Cancer. MGj 2026; 20 (3) : 3
URL: http://mg.genetics.ir/article-1-1890-en.html
URL: http://mg.genetics.ir/article-1-1890-en.html
Ali Yazdanian 
, Amir Mohammad Aghaei , Amir Houshang Hosseinzadeh Moghbeli , Morteza Akbari , Elaheh Maghsoudinia , Habib Zarrehdar , Nima Afshar Moghaddam , Seyed Ahmad Hosseini , Dariush Shanehbandi *
, Amir Mohammad Aghaei , Amir Houshang Hosseinzadeh Moghbeli , Morteza Akbari , Elaheh Maghsoudinia , Habib Zarrehdar , Nima Afshar Moghaddam , Seyed Ahmad Hosseini , Dariush Shanehbandi *
Immunology Research Center
Abstract: (266 Views)
Thyroid cancer is the most common endocrine malignancy worldwide, with the papillary subtype being the most prevalent. Like other common cancers, this malignancy arises from alterations in the molecular mechanisms of normal cells, including cell cycle regulation and programmed cell death. Cyclin-dependent kinases (CDKs), particularly CDK-4 and CDK-6, are major regulators of the cell cycle. In contrast, CDKN2A, another gene involved in cell cycle regulation, negatively regulates cyclin-dependent kinases and thereby prevents uncontrolled cell proliferation. Epigenetic modifications also contribute to the downregulation of gene expression. In several malignancies, promoter methylation of CDKN2A results in decreased gene expression and loss of its regulatory function. Given the critical role of cell cycle dysregulation in carcinogenesis, the present study investigated the expression levels of CDK-4, CDK-6, and CDKN2A, as well as the methylation status of CDKN2A, in thyroid cancer tissue samples from patients in northwestern Iran.
Fifty patients diagnosed with thyroid cancer were enrolled in the study after providing informed consent. The expression levels of CDK-4, CDK-6, and CDKN2A in tumor tissues were compared with those in margin tissues using quantitative real-time PCR (qRT-PCR). The methylation status of the CDKN2A promoter region was evaluated using Methylation-Sensitive High-Resolution Melting (MS-HRM). A p-value < 0.05 was considered statistically significant.
Significant differences were observed in the expression levels of all three genes between tumor and margin tissues. CDK-4 and CDK-6 showed increased expression in tumor tissues, whereas CDKN2A expression was decreased. In addition, CDKN2A promoter methylation was higher in tumor tissues than in margin tissues, which may explain its reduced expression. Furthermore, these molecular alterations were associated with certain clinicopathological characteristics, including lymph node metastasis and distant metastasis.
Our findings suggest that the expression levels of CDK-4 and CDK-6, together with the methylation and expression status of CDKN2A, may serve as potential therapeutic targets or diagnostic and predictive biomarkers in thyroid cancer.
Fifty patients diagnosed with thyroid cancer were enrolled in the study after providing informed consent. The expression levels of CDK-4, CDK-6, and CDKN2A in tumor tissues were compared with those in margin tissues using quantitative real-time PCR (qRT-PCR). The methylation status of the CDKN2A promoter region was evaluated using Methylation-Sensitive High-Resolution Melting (MS-HRM). A p-value < 0.05 was considered statistically significant.
Significant differences were observed in the expression levels of all three genes between tumor and margin tissues. CDK-4 and CDK-6 showed increased expression in tumor tissues, whereas CDKN2A expression was decreased. In addition, CDKN2A promoter methylation was higher in tumor tissues than in margin tissues, which may explain its reduced expression. Furthermore, these molecular alterations were associated with certain clinicopathological characteristics, including lymph node metastasis and distant metastasis.
Our findings suggest that the expression levels of CDK-4 and CDK-6, together with the methylation and expression status of CDKN2A, may serve as potential therapeutic targets or diagnostic and predictive biomarkers in thyroid cancer.
Article number: 3
Type of Study: Applicable |
Subject:
Subject 03
Received: 2025/09/24 | Accepted: 2026/06/7 | Published: 2026/06/14
Received: 2025/09/24 | Accepted: 2026/06/7 | Published: 2026/06/14
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