• Arch Iran Med · Mar 2022

    CpG Island Methylation of the Rap1Gap Gene in Medullary Thyroid Cancer.

    • Bita Faam, Ata A Ghadiri, Mohammad Ali Ghaffari, Mehdi Totonchi, Atieh Amouzegar, Fereidoun Azizi, Hajiehbibi Shahbazian, Mahmoud Hashemitabar, Seyed Ahmad Fanaei, and Layasadat Khorsandi.
    • Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
    • Arch Iran Med. 2022 Mar 1; 25 (3): 171-177.

    BackgroundMedullary thyroid cancer (MTC) is a rare type of neuroendocrine tumor. This study aimed to investigate the gene and protein expression of RAP1GAP and DNA methylation patterns of its CpG74a , CpG74b , and CpG24 in an Iranian population with MTC.MethodsIn this case-control study, we selected 55 individuals who underwent thyroidectomy in Erfan hospital, Tehran, between 2018 and 2020. Samples were divided into normal thyroid tissues (control; n=20), benign nodule (n=20), and MTC (n=15). DNA methylation patterns were investigated using MSP (methylation-specific PCR). The protein level and mRNA expression of RAP1GAP were also evaluated using western blotting and real-time PCR, respectively.ResultsThe hyper-methylation rates of CpG24 and CpG74a in the MTC samples were considerably higher than the controls (83% versus 15% and 74% versus 17%, respectively; P<0.001). The methylation/unmethylation ratio of CpG74a , and CpG24 was considerably higher than the controls (P<0.001). The methylation/unmethylation ratio of CpG24 in the benign nodules was also considerably greater than the controls (P<0.001). The mRNA expression and the protein level of RAP1GAP in the MTC group were considerably lower than the controls (P=0.005 and P=0.035, respectively). In the MTC group, aberrant methylation of CpG74a and CpG24 was significantly correlated with decreasing expression of the Rap1Gap gene (R2 : 0.23; P=0.032 and R2 : 0.56; P=0.001, respectively).ConclusionHyper-methylation in CpG24 and CpG74a and decreasing expression of RAP1GAP can be considered as diagnostic biomarkers for MTC.2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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