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: (9 Views)
Background: 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 molecular mechanisms of normal cells, such as cell cycle regulation and programmed cell death. Cyclin-dependent kinases (CDKs), particularly CDK-4 and CDK-6, are key regulators of the cell cycle. In contrast, CDKN2A, another gene involved in cell cycle control, negatively regulates CDKs, thereby preventing uncontrolled cell proliferation. Epigenetic modifications also play a role in downregulating gene expression. In certain malignancies, promoter methylation of CDKN2A leads to reduced expression and diminished regulatory function. Given the importance of cell cycle dysregulation in carcinogenesis, the present study investigates the expression levels of CDK-4 and CDK-6 and their association with CDKN2A methylation in thyroid cancer tissue samples from patients in northwestern Iran.
Methods: Fifty patients diagnosed with thyroid cancer were enrolled in the study after providing informed consent. Gene expression changes of CDK-4 and CDK-6 in tumor tissues compared to margin (non-tumor) tissues were assessed using quantitative real-time PCR (qRT-PCR). Methylation status of the CDKN2A promoter region was analyzed using Methylation-Sensitive High-Resolution Melting (MS-HRM). A p-value of <0.05 was considered statistically significant.
Results: Significant differences were observed in the expression levels of all three genes between tumor and margin samples. CDK-4 and CDK-6 showed increased expression in tumor tissues, while CDKN2A expression was decreased. Additionally, CDKN2A promoter methylation was higher in tumor samples, potentially explaining its reduced expression. These molecular changes were also found to be associated with certain clinicopathological features, including lymph node metastasis and distant metastasis.
Conclusion: Our findings suggest that the expression levels of CDK-4 and CDK-6, along with CDKN2A methylation and expression status, may serve as potential therapeutic targets or diagnostic/prognostic biomarkers in thyroid cancer.
Methods: Fifty patients diagnosed with thyroid cancer were enrolled in the study after providing informed consent. Gene expression changes of CDK-4 and CDK-6 in tumor tissues compared to margin (non-tumor) tissues were assessed using quantitative real-time PCR (qRT-PCR). Methylation status of the CDKN2A promoter region was analyzed using Methylation-Sensitive High-Resolution Melting (MS-HRM). A p-value of <0.05 was considered statistically significant.
Results: Significant differences were observed in the expression levels of all three genes between tumor and margin samples. CDK-4 and CDK-6 showed increased expression in tumor tissues, while CDKN2A expression was decreased. Additionally, CDKN2A promoter methylation was higher in tumor samples, potentially explaining its reduced expression. These molecular changes were also found to be associated with certain clinicopathological features, including lymph node metastasis and distant metastasis.
Conclusion: Our findings suggest that the expression levels of CDK-4 and CDK-6, along with CDKN2A methylation and expression status, may serve as potential therapeutic targets or diagnostic/prognostic biomarkers in thyroid cancer.
Article number: 3
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