Although thyroid cancer (TC) is a rare cancer with a rate of 2.1%, it is the most common cancer type among endocrine tumors. The molecular mechanisms of thyroid cancer, which develops as a result of environmental and genetic factors, are still unclear. SOX family genes are transcription factors that are expressed in a tissue-specific manner and play a role in the developmental processes. SRY-box transcription factor 15 (SOX15) is an important member of the SOX family and is involved in carcinogenesis. Its downregulation has been associated with the development and progression of different human malignancies. Some SOX family members have been reported to control cell proliferation by acting as negative regulators of the Wnt/β-catenin signaling pathway. MYC, CCND1 and CTNNB1 genes are important components of the Wnt signaling pathway. Recently, we have shown that epigenetic silencing of the SOX15 gene is associated with the pathogenesis of papillary thyroid carcinoma,In the present study, to further the understanding of the molecular mechanisms of SOX15 in papillary thyroid carcinoma (PTC) we investigated SOX15 expression in association with the transcriptional targets of the Wnt/β-catenin pathway.Primary thyroid tumors and adjacent nonmalignant tissue samples were collected from 52 patients, prior to any treatment. Total RNA was isolated from tissue samples and reverse transcription was performed. Expression levels of the SOX15, CTNNB1, c-MYC and CCND1 genes were analyzed by qRT-PCR using the SYBR green and Light-Cycler 480 system (Roche Diagnostics, Germany). β2M was used as the reference to normalize the mRNA levels. Statistical analysis was performed using the SPSS 21.0 (IBM® SPSS® Statistics, IBM Corporation Somers, NY, USA) program.SOX15 gene expression was significantly downregulated in 64.6% of PTC tissues compared to their normal counterparts. In contrast, CCND1, CTNNB1 and c-MYC gene expressions were significantly upregulated in 70.2%, 60% and 57.8% of the patients. Among the group of patients with downregulated SOX15 expression CCND1, CTNNB1 and c-MYC expression were upregulated in 46.8%, 40% and 40% of the subjects, respectively. Our data suggest that SOX15 downregulation may contribute to activation of Wnt signaling and provides further evidence indicating involvement of SOX15 in modulating the Wnt/β-catenin pathway in thyroid carcinogenesis. Citation Format: Ayse Nur Buyru, Ayşegul Soysal, Ahmet Ozaydın, Betul Seyhan, Soykan Arıkan, Nejat Dalay. Expression of SOX15 and Wnt pathway genes in papillary thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 776.
Background The adrenergic system plays a central role during the clinical course of hypertrophic cardiomyopathy (HCM) and hence beta-blocker therapy is the first-line treatment option according to current guidelines. Previous studies demonstrated variable cellular response to an adrenergic stimulus due to adrenoceptor-1 (ADRB-1) gene polymorphism in several patient groups including hypertension and dilated cardiomyopathy. Moreover, the impact of beta-blockers is also variable in these patients. Purpose We aimed to investigate the impact of ADRB-1 gene polymorphism on structural and functional features among patients with HCM. Methods In this study, we investigated the roles of Arginin389Glycine and Glycine49Serine polymorphism. Patients with a clear diagnosis of HCM according to current guidelines were included. Structural features including maximal wall thickness, interstitial fibrosis and left ventricular/atrial volumes were obtained using cardiac MRI and transthoracic echocardiography. Functional features including heart rate, blood pressure, left ventricular outflow obstruction were also recorded. The risk of sudden cardiac death was calculated using the HCM risk score. The impact of beta-blocker therapy on heart rate and blood pressure were also compared. Results After the exclusion of patients, 147 patients were included in the study. 77% of the study population were male and the mean age was 49.5 years. The hypertrophic segment was septum in 83% of the study population. The mean maximum wall thickness was 20 mm (19–23). With respect to Ser49Gly polymorphism, Serine homozygotes demonstrated higher late-gadolinium enhancement and indicator of interstitial fibrosis (p: 0.007). In concordance with higher LGE, the presence of fragmented QRS on surface ECG (p: 0.026) and a higher prevalence of non-sustained ventricular tachycardia (p: 0.016) in these patients were observed. The risk of sudden cardiac death was also higher in Ser49 homozygotes (p: 0.041). However, with respect to Arg389Gly gene polymorphism, there was no significant difference between Arg389 homozygotes, Arg389Gly heterozygotes and Gly389 homozygotes in terms of structural and functional features. The vast majority of patients reported improved functional capacity and decreased shortness of breath during the follow-up regardless of ADRB-1 gene polymorphism which is objectively validated by decreased pro-BNP levels in all patients. Conclusion Our results indicated that ADRB-1 gene polymorphism, particularly Ser49Gly gene polymorphism may have a significant role during the clinical course of HCM. Since Ser49 homozygote patients demonstrated higher interstitial fibrosis and a higher risk of sudden cardiac death, further studies are required to determine the significance of Ser49Gly gene polymorphism in HCM patients. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Bilimsel Arastırma Projesi (BAP) - Istanbul University - Cerrahpasa, Cerrahpasa Medical School
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